Luigi Fabbrizzi1. 1. Dipartimento di Chimica, Università di Pavia, 27100 Pavia, Italy.
Abstract
In 1864, Hugo Schiff, aged 30, discovered the reaction of aromatic aldehydes with primary amines to give imine derivatives. A C═N imine bond presents the unique properties of being strong, as expected for a covalent double bond, and of being reversible due to a fast hydrolytic process. In view of such features, Schiff base condensations are thermodynamically controlled, which, in the case of reactions involving multifunctional aldehydes and primary amines, allow the formation of complex and sophisticated structures through a trial-and-error mechanism. Back hydrolysis can be prevented by hydrogenating C═N bonds under mild conditions. In such a way, stable rings and cages of varying sizes can be synthesized. Moreover, transition and post-transition metal ions, establishing coordinative interactions with imine nitrogen atoms, can address Schiff base condensations of even more complex molecular systems, whose structure is controlled by the geometrical preferences of the metal. Metal template Schiff base condensations have produced multinuclear metal complexes exhibiting the shape of tetrahedral containers, of double helices, and, supreme wonder, of the Borromean rings. These molecular objects cannot be compared to the masterpieces of painting and sculpture of the macroscopic world, but they instill in the viewer aesthetical pleasure and admiration for their creators.
In 1864, pan class="Gene">Hugopan class="Chemical">Schiff, aged 30, discovered the reaction of aromatic aldehydes with primary amines to give imine derivatives. A C═N imine bond presents the unique properties of being strong, as expected for a covalent double bond, and of being reversible due to a fast hydrolytic process. In view of such features, Schiff base condensations are thermodynamically controlled, which, in the case of reactions involving multifunctional aldehydes and primary amines, allow the formation of complex and sophisticated structures through a trial-and-error mechanism. Back hydrolysis can be prevented by hydrogenating C═N bonds under mild conditions. In such a way, stable rings and cages of varying sizes can be synthesized. Moreover, transition and post-transition metal ions, establishing coordinative interactions with iminenitrogen atoms, can address Schiff base condensations of even more complex molecular systems, whose structure is controlled by the geometrical preferences of the metal. Metal template Schiff base condensations have produced multinuclear metal complexes exhibiting the shape of tetrahedral containers, of double helices, and, supreme wonder, of the Borromean rings. These molecular objects cannot be compared to the masterpieces of painting and sculpture of the macroscopic world, but they instill in the viewer aesthetical pleasure and admiration for their creators.
In March 1864, pan class="Gene">Hugo pan class="Chemical">Schiff (30), an assistant at the Chair of Chemistry
at the University of Pisa, held by Professor Paolo Tassinari (1829–1909),
submitted to Annalen der Chemie und Pharmacie a paper
entitled “Mittheilungen aus dem Universitäts-laboratorium
in Pisa” (Communications from the University Laboratory in
Pisa).[1] He was about to leave Pisa for
the Regio Istituto di Studi Superiori Pratici e di Perfezionamento
(Royal Institute for Practical and Advanced Studies) in Florence,
where he had been nominated Professor of Chemistry, the first in the
Institute. In the article, Schiff provided an account of the research
work that he had carried out during his one year stay in Pisa. The
paper (seven and one-half pages) consists of two sections: one (six
pages) reported on quinolin and on its metal derivatives (Zn, Hg,
Sb, and Bi), “Untersuchungen über das Chinolin”
(Investigations on Quinolin), and the second section, one and a half
pages, “Eine neue Reihe organischer Basen” (A new series
of organic bases), described the reactions of aniline with aldehydes. Figure shows a chemical
equation directly taken from the paper, in which 2 mol of aniline
reacts with 2 mol of an aldehyde, whether aliphatic or aromatic, to
give 1 mol of base and 2 mol of water.
Figure 1
Reaction of aniline with
an aldehyde (1) as depicted in Schiff’s
1864 article,[1] (2) same reaction as 1,
with the structural formulae of aniline and the Schiff base, and (3)
reaction of aniline and benzaldehyde, illustrated according to the
modern view. The reactions were drawn by the author using ancient
and modern fonts.
Reaction of pan class="Chemical">aniline with
an pan class="Chemical">aldehyde (1) as depicted in Schiff’s
1864 article,[1] (2) same reaction as 1,
with the structural formulae of aniline and the Schiff base, and (3)
reaction of aniline and benzaldehyde, illustrated according to the
modern view. The reactions were drawn by the author using ancient
and modern fonts.
The [2 + 2] stoichiometry
of reaction 1 is pan class="Gene">surprising to modern
chemists, who correctly interpn>ret n>an class="Chemical">Schiff base condensation according
to reaction 3, in which aniline and benzaldehyde react according to
a [1 + 1] stoichiometry to give an imine derivative and a water molecule.
In a later paper,[2] Schiff provided the
structural formula of the product of the condensation, as illustrated
in reaction 2. In particular, Schiff hypothesized for the base a cyclic
structure to allow nitrogen to achieve its typical valence. Schiff
did not know the double bond and could not envision the formation
of the imine bond. Moreover, it should be noted that in the original
equation (reaction 1), both C and O symbols are barred by a short
horizontal line, which conventionally indicates that this atom stands
for two equivalents (O, 2 × 8; C, 2 × 6). At the Karlsruhe
Congress (3–5 September 1860), Stanislao Cannizzaro (1826–1910)
proposed a new scale of atomic weights, based on the assumption that
hydrogen exists as a diatomic molecule (H2) and possesses
a molecular weight = 2.00.[3] Cannizzaro’s
scale was adopted by most of the chemists, and bar convention persisted
for a few more years, whereupon the bars were dropped. Schiff, aged
26 (Figure ), participated
in the Karlsruhe Congress but in 1864 still adhered to the bar convention.
In Karlsruhe, Schiff met Cannizzaro, with whom he later collaborated
in giving a sound and well-defined framework to Italian chemistry
and founded the first Italian chemical magazine (Gazzetta
Chimica Italiana, 1870). Among the 127 attendants of the
Congress, German chemists represented the most numerous group (57)
followed by chemists from France (21) and from United Kingdom (18).
Quite curiously, Schiff was not considered a member of the German
team but of the Swiss one (6) because at that time, he was a Privatdozent
at the University of Bern.
Figure 2
Picture of Hugo Schiff (Frankfurt am Main, 26
April 1834–Florence,
8 September 1915), taken in 1860. In that year Schiff, a Privatdozent
at the University of Bern, attended the Karlsruhe Congress (3–5
September 1860), the first international conference of chemistry worldwide.
Public domain image; source: http://www.biospektrum.de/blatt/d_bs_pdf&_id=932204.
pan class="Chemical">Picture of pan class="Gene">Hugo Schiff (Frankfurt am Main, 26
April 1834–Florence,
8 September 1915), taken in 1860. In that year Schiff, a Privatdozent
at the University of Bern, attended the Karlsruhe Congress (3–5
September 1860), the first international conference of chemistry worldwide.
Public domain image; source: http://www.biospektrum.de/blatt/d_bs_pdf&_id=932204.
Settled in Florpan class="Chemical">ence, at the end
of December 1864, Schiff submitted
to Annalen the complete paper (Eine neue Reihe organischer
Diamine, 28 pages)[4] followed by a paper
on the same topic (Eine neue Reihe organischer Diamine – ZweiteAbtheilung, 45 pages),[5] submitted on April
1866. Still, in 1866, Schiff published an Italian version of his studies
on the same topic (“Sopra una nova serie di basi organiche”
[On a new series of organic bases])[2] in
a scientific-economic magazine published in Palermo (Giornale
di scienze naturali ed economiche). At that time, Cannizzaro,
a professor at the University of Palermo, used to publish some of
his papers in Giornale and may have stimulated his
colleague and friend Schiff to submit articles. Quite interestingly,
in the paper, bars dropped from C and O symbols, perhaps because Schiff
wanted to please his friend Stanislao, more probably because the local
typographer did not have available such typefaces. Noticeably, in
the same issue, there was also an inorganic paper by Schiff, “Cenni
di chimica mineralogica” (Elements of Mineralogical Chemistry),
which demonstrated the versatility and the variety of interests of
the author. After the 1864–1866 period, Schiff, eager to explore
new and unknown fields of organic and inorganic chemistry, was not
any longer interested on his bases. Nevertheless, he had sown a precious
seed from which a vigorous plant grew and is still growing.
Schiff Bases and Coordination Chemistry
pan class="Chemical">Schiff bases
are classical ligands for pan class="Chemical">metal ions of p, d, and
f blocks, which have significantly contributed to the development
of coordination chemistry on both basic and applicative aspects, with
a special reference to catalysis. The first metal complex of a Schiff
base was synthesized by Alphonse Combes (1854–1907), a professor
of Industrial Chemistry at the École Municipale de Physique
et de Chimie in Paris.[6] Combes in 1889
made ethylenediamine react with two equivalents of acetylacetone,
as pure substances. A highly exothermic reaction took place, with
formation of water and, on cooling, precipitation of a white crystalline
mass (m.p. of 111 °C). Figure shows the structural formula of the product as drawn
by Combes (a) compared with that outlined in a modern style (b).
Figure 3
(a) Formula
of the product of the reaction of ethylenediamine (1
equiv) and acetylacetone (2 equiv), as drawn by Combes.[6] (b) Schiff base condensation written according
to the modern view. The reactions were drawn by the author using ancient
and modern fonts.
(a) Formula
of the product of the reaction of n class="Chemical">pan class="Chemical">ethylenediamine (1
equiv) and class="Chemical">n>an class="Chemical">acetylacetone (2 equiv), as drawn by Combes.[6] (b) Schiff base condensation written according
to the modern view. The reactions were drawn by the author using ancient
and modern fonts.
At that time, multiple
bonds were already known to chemists, and
pan class="Chemical">Combes wrote correctly the formula of the product (1 in Figure a). The reaction
is a classical pan class="Chemical">Schiff base condensation (but Schiff was not cited
in the article) involving two ketonic carbonyl groups and two primary
amine groups, with formation of two imine bonds and elimination of
two water molecules. Combes disregarded the current accepted nomenclature
and used for nitrogen the symbol Az (from azote), introduced by Lavoisier
in 1772. He also indicated the number of a given atom in a formula
with a superscript, definitively replaced by a subscript in a short
time.
Thpan class="Chemical">en, on treating an aqueous solution of white product 1 with an aqueous solution of n>an class="Chemical">copper(II) acetate, a nice violetprecipitate
was obtained, in the form of thin plates, insoluble in water, and
fairly soluble in ethanol and chloroform. On the basis of the gravimetric
analysis of copper(II), Combes suggested the molecular formula C12H18N2O2Cu (right) and the
structural formula shown in Figure a (wrong).
Figure 4
(a) Structural formula proposed by Combes for
the neutral complex
obtained through the reaction of copper(II) acetate with Schiff base 1, shown in Figure a.[6] (b) Schiff base 1 (keto form) undergoing a tautomeric equilibrium of constant KT to give enol form 2. In the presence
of a base (e.g., acetate), 2 (H2L) deprotonates,
and the enolate ion L2– forms stable neutral complex 3, [CuII(L)]. The reactions were drawn by the author
using ancient and modern fonts.
(a) Structural formula proposed by pan class="Chemical">Combes for
the neutral compn>lex
obtained through the reaction of pan class="Chemical">copper(II) acetate with Schiff base 1, shown in Figure a.[6] (b) Schiff base 1 (keto form) undergoing a tautomeric equilibrium of constant KT to give enol form 2. In the presence
of a base (e.g., acetate), 2 (H2L) deprotonates,
and the enolate ion L2– forms stable neutral complex 3, [CuII(L)]. The reactions were drawn by the author
using ancient and modern fonts.
pan class="Chemical">Combes was aware of the acidic nature of the −Cpan class="Chemical">H2– groups linked to the carbonyl group and to the imine group
and correctly hypothesized their deprotonation in the presence of
a base (e.g., acetate) but did not know the existence of the keto–enol
tautomerism (Figure b). Thus, he hypothesized the formation of CuII–C
bonds. The monumental work by Alfred Werner (1866–1919) on
metal coordination chemistry would be published four years later,[7] and Combes could not know that transition metal
ions do not have any affinity toward carbon donor atoms but are eager
to interact with nitrogen donor atoms and oxygen donor atoms especially
if detaining a formal negative charge.
pan class="Chemical">Enoln> form 2 in Figure b is a
close relative of pan class="Chemical">salen (4, in Figure ), a classic ligand
of transition and post-transition pan class="Chemical">metals and a major player on the
coordination chemistry stage.[8]
Figure 5
Synthesis of
salen (4) through Schiff base condensation
of ethylenediamine and salycylaldehyde. In a basic solution, salen
releases two hydrogen ions and chelates a divalent metal ion to give
a stable neutral complex (5, [CoII(L2–)0]). Tsumaki in 1938 observed that [CoII(L2–)] is able to bind reversibly a dioxygen molecule,
the first example of an artificial O2 carrier,[9] thus opening one of the most intensively cultivated
fields of coordination chemistry.
Synthesis of
pan class="Chemical">salen (4) through pan class="Chemical">Schiff base condensation
of ethylenediamine and salycylaldehyde. In a basic solution, salen
releases two hydrogen ions and chelates a divalent metal ion to give
a stable neutral complex (5, [CoII(L2–)0]). Tsumaki in 1938 observed that [CoII(L2–)] is able to bind reversibly a dioxygen molecule,
the first example of an artificial O2 carrier,[9] thus opening one of the most intensively cultivated
fields of coordination chemistry.
pan class="Chemical">Salen is obtained by pan class="Chemical">Schiff base condensation of 2
equiv of salycylaldehyde and 1 equiv of ethylenediamine
(en). On addition of divalent metal acetate, the two
phenolic −OH of H2L deprotonate, and L2– forms a neutral complex with MII ([MII(L2–)]0, 5). The complex is strongly
stabilized by the chelate effect. Cobalt(II) complexes of salen derivatives
were the first synthetic complexes capable of absorbing and releasing
reversibly dioxygen,[9] thus mimicking natural
oxygen carriers and storage proteins containing a transition metal,
to which the oxygen reversibly coordinates: iron (FeII/FeIII: myoglobin and hemoglobin) and copper (CuI/CuII: hemocyanin). Figure shows the crystal structures of a cobalt(II) salen complex
and of its oxygenated form.[10]
Figure 6
Crystal structures
of cobalt salen complexes: (a) N,N′-ethylene-bis(3-tert-butylsalicylideneiminato)-cobalt(II)[10] and (b) dioxygen-(N-pyridine)-N,N′-ethylene-bis(3-tert-butylsalicylideneiminato)-cobalt(III).[10] In pyridine solution, O2 oxidizes CoII to
CoIII and is reduced to O2– (superoxide). The process is described by the following equation:
[CoII(salen)] + py + O2 ⇆ [CoIII(salen)(py)(O2–)].
Crystal structures
of pan class="Chemical">cobalt salen complexes: (a) N,N′-ethylpan class="Chemical">ene-bis(3-tert-butylsalicylideneiminato)-cobalt(II)[10] and (b) dioxygen-(N-pyridine)-N,N′-ethylene-bis(3-tert-butylsalicylideneiminato)-cobalt(III).[10] In pyridine solution, O2 oxidizes CoII to
CoIII and is reduced to O2– (superoxide). The process is described by the following equation:
[CoII(salen)] + py + O2 ⇆ [CoIII(salen)(py)(O2–)].
At room temperature, a red-pan class="Chemical">brown square planar pan class="Chemical">cobalt(II) complex
(a in Figure ), dissolved in pyridine, absorbs dioxygen to give dark brown
complex b. The process involves an electron transfer
from CoII to O2, and b must be
correctly described as a [CoIII(salen)(py)(O2–)], in which the superoxide anion is bound to
CoIII. The system absorbs O2 at room temperature
and releases it at higher temperature. This cycle may be repeated
many times, although the activity of the complex toward dioxygen uptake
slowly decreases on continued cycling, owing to decomposition.[10]
The Paradoxical Nature of
the C=N Bond,
Both Strong and Labile
Figure illustrates
the mechanism of the reaction of the pan class="Chemical">carbonyl group of an n>an class="Chemical">aldehyde
with a primary amine.
Figure 7
Mechanism of the reaction of the carbonyl group of an
aldehyde
with a primary amine operating in Schiff base condensations. The process
is constituted by three reversible steps.
Mechanism of the reaction of the pan class="Chemical">carbonyl group of an
n>an class="Chemical">aldehyde
with a primary amine operating in Schiff base condensations. The process
is constituted by three reversible steps.
The reaction proceeds through three reversible steps: (i) nucleophilic
attack by the pan class="Chemical">amine n>an class="Chemical">nitrogen atom to the carbonyl carbon atom, to
give separated charge intermediate 6; (ii) intramolecular
proton transfer from the ammonium group to the carbinolate group to
give carbinolamine 7; (iii) water elimination and imine
formation. The entire process is fully reversible. It derives that
the C=N bond, strong as expected for a double covalent bond
(C=N bond energy of 615 kJ mol–1), is subject
to hydrolysis according to the reverse equilibrium in Figure , and its formation is therefore
thermodynamically controlled. Covalent bonds in organic substances
are typically slow both to form and to break. Thus, it is inert and
irreversible, and its formation occurs under a kinetic control. On
the other hand, there exists in nature a variety of reversible bonding
interactions, e.g., hydrogen bonds: they are weak, reversible, fast
to form, fast to break and operate under a thermodynamic control.
The imine bond is unique: it is strong (it is a covalent bond and,
what is more, double) and labile (like the hydrogen bond). Such a
dual feature allows the synthesis of complex molecular systems from
aldehydes and primary amines in a one-pot procedure: the reactants,
put all together in the same vessel, undergo an unlimited sequence
of fast and reversible attempts to finally give the desired product
in good yield, as long as it is thermodynamically stable.
A
convincing example is n class="Chemical">provided by the reaction shown in Figure , leading to a cage-shaped
macropan class="Chemical">bicyclic compn>ound.
Figure 8
Schiff base condensation of two molecules of
branched tetramine
tren with three molecules of 1,3-benzene-dicarbaldehyde, to give unsaturated
cage-shaped molecule 8, whose six C=N bonds are
subject to hydrolysis. Imine bonds are then hydrogenated to give kinetically
stable octamine 9, bistren.
pan class="Chemical">Schiff basen> condpan class="Chemical">ensation of two molepan class="Chemical">cules of
branched tetramine
tren with three molecules of 1,3-benzene-dicarbaldehyde, to give unsaturated
cage-shaped molecule 8, whose six C=N bonds are
subject to hydrolysis. Imine bonds are thenhydrogenated to give kinetically
stable octamine 9, bistren.
Two molepan class="Chemical">cules of pan class="Chemical">branched tetramine tren are allowed to react with
three molecules of 1,3-benzene-dicarbaldehyde in methanol at room
temperature. After a few minutes, Schiff base 8 precipitates
as a white product. Such a product is not definitively stable, as
it is subject to the reverse equilibrium, which restores the reactants,
for instance, on addition of an acid. However, the six vulnerable
C=N bonds can be “immobilized” through hydrogenation
with NaBH4 to give cage-shaped macrobicyclic tetramine 9. C–N bonds are weaker than corresponding C=N
bonds (C–N bond energy of 290 kJ mol–1) but
are inert and not prone to hydrolysis. In fact, cage-shaped octamine
is stable both in strongly acidic and in strongly basic solutions.
That as many as five particles spontaneously organized to give a complex
structure is due to the reversible nature of the imine bonds. C=N
bonds form (through Schiff base condensation) and break (through hydrolysis)
unceasingly and quickly until, through a trial-and-error mechanism,
the most thermodynamically stable structure is obtained: the hexaimine
cage. The reason of such stability is not straightforward: it is possible
that benzene residues in the cage are less exposed to the protic medium
(MeOH) than in the dialdehyde, thus exerting a lower disturbing effect
on solvent’s aggregation, which displaces to the right the
condensation equilibrium.
The size of the cavity of the pan class="Chemical">bistrenn>
cage can be modulated at
will by choosing the appropriate dialdehyde, which generates the appropriate
spacer. A series of spacers used in the synthesis of bistren cages
is shown in Figure .[11−14]
Figure 9
Bistren
cages with varying spacers. Each spacer derives from the
aldehyde used in the Schiff base condensation and defines the size
of the cavity.
pan class="Chemical">Bistrenn>
cages with varying spacers. Each spacer derives from the
aldehyde used in the Schiff base condensation and defines the size
of the cavity.
Bistrens: Comfortable Cages
for Anions
pan class="Chemical">Bistren cages can act as containers of pan class="Chemical">anions
of varying sizes
and shapes. However, if you wish to include a negatively charged particle,
you must make the shelter appropriate for it, for instance, creating
a positive charge inside. In particular, in aqueous solution adjusted
to pH 3, the six secondary nitrogen atoms of bistren are protonated,
and the two pivot tertiary amine groups are not. At this stage, the
hexammonium receptor can accommodate the anion, provided that there
exists steric complementarity between the hosting cavity and the guest.
The process takes place in two steps, as illustrated by a cascade
diagram illustrated in Figure , in which the hexaprotonated form of bistren 10 incorporates the ClO4– anion.
Figure 10
Cascade
mechanism for the inclusion of ClO4– into
the hexaprotonated form (LH66+) of bistren 10, to give the inclusion complex [LH66+·(ClO4–)]5+. C–H
hydrogens, solvating molecules, and counteranions have been omitted
for clarity.
Cascade
mechanism for the inclusion of pan class="Chemical">ClO4– into
the hexaprotonated form (n>an class="Chemical">LH66+) of bistren 10, to give the inclusion complex [LH66+·(ClO4–)]5+. C–H
hydrogens, solvating molecules, and counteranions have been omitted
for clarity.
Single crystal X-ray diffraction
studies have shown that void pan class="Chemical">octamine
L (10) has a rather elongated ellipsoidal shapn>e, with
a distance betwen>an class="Chemical">en the two tertiary nitrogen atoms Ntert···Ntert = 11.13 Å.[15] On protonation, to give LH66+, the
reciprocal electrostatic repulsions between the six ammonium groups
forces the framework to assume a spheroidal shape, with a substantial
reduction of the Ntert···Ntert distance (9.32 Å).[16] On inclusion
of ClO4–, to form the inclusion complex
[LH66+·(ClO4–)]5+, such a distance does not change very much (Ntert···Ntert = 9.85 Å), thus
maintaining its spheroidal shape.[17] However,
the framework readjusts to point the N–H fragments of the ammonium
groups toward the oxygen atoms of perchlorate. The establishing of
electrostatic interactions and of hydrogen bonds between the highly
polarized N–H fragments and perchlorateoxygen atoms are responsible
for the stability of the complex both in acidic aqueous solution and
in the solid state. LH66+ (L = 10) shows a special affinity toward tetraoxo anions and forms stable
inclusion complexes with SO42–, SeO42–, ReO4–,
and TcO4– and, in addition, with tetrahedral
anion S2O32–.[18] In all the anion inclusion complexes, the hexammonium receptor
exhibits a spheroidal shape with an Ntert···Ntert distance of ca. 10 Å.
However, pan class="Chemical">LH66+n> (L = 10) possesses
a rather flexible framework and is able to shrink its cavity enough
to incorporate a monoatomic anion. This is the case for the pan class="Chemical">bromide
inclusion complex, whose structure is shown in Figure a.[19]
Figure 11
Crystal structures
of the inclusion complexes of LH66+ (L = 10) with (a) Br–,[19] (b) Cl–,[20] and (c)
F–.[21]
Crystal structures
of the inclusion complexes of n class="Chemical">pan class="Chemical">LH66+ (L = 10) with (a) pn>an class="Chemical">Br–,[19] (b) Cl–,[20] and (c)
F–.[21]
In order to establish strong electrostatic and pan class="Chemical">hydrogen bonding
interactions with pan class="Chemical">Br– (ionic radius of 1.96 Å),
the hexammonium cage shrinks its cavity to a very short Ntert···Ntert distance of 6.47 Å. The inclusion
of the smaller Cl– ion (ionic radius of 1.81 Å)
would require a further contraction of the cavity, which would involve
a too high energy cost. Thus, in order to fit the cavity in its relaxed
conformation, chlorideenters the cage accompanied by a water molecule
(see Figure b).[20] Each guest occupies and interacts with a trenH33+ subunit. H2O is a cooperative guest,
which receives six H-bonds from facing N–H fragments but also
donates an H-bond from one of its O–H fragments to the close
Cl– anion. Moreover, in the case of the smallest
fluoride ion (ionic radius of 1.28 Å), in the relaxed hexammonium
cage, there is room for two F– anions bridged by
a water molecule (see Figure c).[21] H2O is there to
fill the cavity and to shield the electrostatic repulsions between
the two fluoride ions. Thus, hexaprotonated bistren cages are versatile
anion receptors, which are capable to rearrange their framework to
fulfill guests’ geometrical requirements. They do not show
any size and shape selectivity in anion inclusion, a behavior that
can be ascribed to the intrinsic weakness and poor directionality
of electrostatic and hydrogen bonding interactions.
There exists
another way to make the pan class="Chemical">bistren cavity appropn>riate
for n>an class="Chemical">anions: putting in the cage two transition metal ions, each interacting
with one bistren subunit. Between the two metals, there is room for
an ambidentate anion capable to act as a bridge. Moreover, the intermetallic
distance can be modulated by varying the length of the spacer, which
may generate selectivity in anion inclusion and recognition. Again,
we are in the presence of a cascade process, which is illustrated
in Figure .[18]
Figure 12
Cascade mechanism for the formation of the ternary dinuclear
complex
[CuII2(L)(N3)]3+ (L = 10, a). The azide ion displacing the two metal-bound water
molecules in the [CuII2(L)(H2O)2]4+ complex (b)[22] and
bridging the two CuII ions to give [CuII2(L)(N3)]3+ (c).[23] (d) Structure of the [CuII(tren)(N3)]+ complex,[24] showing the bent coordination
mode of N3– (CuII–N–N
angle = 116°), ascribed to the sp2 hybridization of
metal-bound nitrogen atoms. (e) Trigonal bipyramidal geometry of a
[CuII(tren)X] + complex (X– = mononegative
anion).
Cascade mechanism for the formation of the ternary dinuclear
complex
pan class="Chemical">[CuII2(L)(N3)]3+ (L = 10, a). The pan class="Chemical">azide ion displacing the two metal-bound water
molecules in the [CuII2(L)(H2O)2]4+ complex (b)[22] and
bridging the two CuII ions to give [CuII2(L)(N3)]3+ (c).[23] (d) Structure of the [CuII(tren)(N3)]+ complex,[24] showing the bent coordination
mode of N3– (CuII–N–N
angle = 116°), ascribed to the sp2 hybridization of
metal-bound nitrogen atoms. (e) Trigonal bipyramidal geometry of a
[CuII(tren)X] + complex (X– = mononegative
anion).
In the first step, in an aqueous
solution of a transitionpan class="Chemical">metal
pan class="Chemical">salt, e.g., Cu(ClO4)2, octamine cage 10 uptakes two CuII ions. Each metal ion goes to occupy
a tren subunit. Copper(II) complexes of branched tetramine tren typically
show a trigonal bipyramidal geometry, with the primary nitrogen atoms
of tetramine spanning the three equatorial positions and the tertiary
one positioned in one axial position. The remaining axial site is
occupied by a fifth donor atom of an exotic ligand (see Figure e). In particular,
in the dimetallic complex in water, the two available axial positions
are occupied by two H2O molecules (Figure b). Such a coordinative arrangement has
been observed in the solid state.[22] Then,
on addition of a polyatomic ambidentate ligand, e.g., azide, the two
water molecules are displaced and replaced by the two terminal nitrogen
atoms of the anion, to give the ternary complex [CuII2(L)(N3)]3+ (Figure c).[23] The azide
ion, which in the [CuII(tren)(N3)]+ complex exhibits a bent coordination mode (Cu–N–N
angle = 116.2°),[24] due to the sp3 hybridization of the terminal nitrogen atoms (see Figure d), in the dimetallic
complex is sterically forced to be collinear with the two CuII ions as well as with the two nitrogen tertiary atoms of bistren.
pan class="Chemical">Bistrens with larger spn>acers can include large organic n>an class="Chemical">anions.
For instance, the hexaprotonated LH66+ and the
dicopper(II) [CuII2(L)]4+ derivatives
of 16 incorporate selectively aromatic and linear aliphatic
dicarboxylates of varying lengths. Figure a,b shows the crystal structures of the
inclusion complexes of LH66+ with terephthalate[25] and of [CuII2(L)]4+ with terephthalate (a and b) and adipate (Figure c).[26]
Figure 13
Crystal structures of dicarboxylate inclusion complexes by receptors
derived from bistren 10 (= L): (a) [LH6·(terephthalate)]4+.[25] (b) [CuII2L·(terephthalate)]2+.[26] (c) [CuII2L·(adipate)]2+.[26]
Crystal structures of pan class="Chemical">dicarboxylate inclusion complexes by recepn>tors
derived from n>an class="Chemical">bistren 10 (= L): (a) [LH6·(terephthalate)]4+.[25] (b) [CuII2L·(terephthalate)]2+.[26] (c) [CuII2L·(adipate)]2+.[26]
In all the complexes,
the cage undergoes a significant conformational
rearrangempan class="Chemical">ent to afford the formation of the strongest interactions,
whether electrostatic/pan class="Chemical">hydrogen bonding or metal–ligand. A major
rearrangement is observed in the [CuII2L·(adipate)]2+ complex, which exhibits the shortest Ntert···Ntert distance and shows a spheroidal shape.
Equilibrium
studies in an aqueous solution buffered at pH = 6,
with n>an class="Chemical">pyridine + CF3COOD, 10–2 M, showed
that log K values for the inclusion by LH66+ of linear aliphatic carboxylates of formula –OOC–(CH2)–COO– (n = 2–6) are nearly the same,
indicating a lack of inclusion selectivity (see open circles in Figure ).[25] On the other hand, equilibrium studies in a 50/50 water/ethanol
(v/v) solution showed that the dimetallic receptor [CuII2(L)]4+ exerts a well-defined inclusion selectivity
for adipate (n = 4). Linear aliphatic dicarboxylates
of lower and higher length do not fit so well with the receptor’s
intermetallic distance and show inclusion constants of 2–3
orders of magnitude smaller (see open triangles in Figure ).[26]
Figure 14
L = 16. Plot of the log K values
vs. the number of methylene groups n of the α,ω-dicarboxylic
acids of formula –OOC(CH2)COO– (A2–). The
log K values refer to the equilibria: (i) empty circles,
LH66+ + A2– ⇄ [LH6···A]4+ (L = 6), pH
6, 20 °C; (ii) empty triangles, [CuII2(L)]4+ + A2– ⇄ [CuII2(L)(A)]2+, 50/50 water/ethanol, pH 7.2, 25 °C. Full
symbols indicate log K values for the inclusion of
terephthalate by [CuII2(L)]4+ (triangle)
and by A2− (circle).
L = 16. pan class="Chemical">Pn>lot of the log K values
vs. the number of methylpan class="Chemical">ene groups n of the α,ω-dicarboxylic
acids of formula –OOC(Cpan class="Chemical">H2)COO– (A2–). The
log K values refer to the equilibria: (i) empty circles,
LH66+ + A2– ⇄ [LH6···A]4+ (L = 6), pH
6, 20 °C; (ii) empty triangles, [CuII2(L)]4+ + A2– ⇄ [CuII2(L)(A)]2+, 50/50 water/ethanol, pH 7.2, 25 °C. Full
symbols indicate log K values for the inclusion of
terephthalate by [CuII2(L)]4+ (triangle)
and by A2− (circle).
Chemists are oftpan class="Chemical">en inclined to give molepan class="Chemical">cular systems names borrowed
from everyday life. Bistren receptors belong to the family of cages.
Cages are familiar objects for the human kind since the Neolithic
Age. Since then, humans have built and used cages but did not love
them for several reasons: (i) cages are a symbol of forced constriction
and freedom deprivation for living beings, (ii) they exhibit to the
public private details of the imprisoned individual, affirming its
state of weakness and dependence, (iii) typical guests of cages are
tender and undefended beings (a canary or a parrot). Humans use cages
mostly for leisure but are not proud of this practice and are reluctant
to its emphasis. It is probably for this reason that artists have
not been inspired by cages, in both painting and handicraft. There
are probably only two relevant paintings featuring a cage, and they
are quite recent on the timescale of art history. One has been painted
by René Magritte (1898–1967)—Elective
Affinities, 1933, shown in Figure . The prisoner of the cage is an egg, and
probably, the artist intended to bewilder the viewer by illustrating
the delayed affinity of two objects to each other, the cage and the
egg, from which the typical guest of the cage, a bird, originates.
Perhaps, the painting intends to communicate a distrustful message:
every human, even before his birth, is destined to live within the
narrow limits and the severe rules of a merciless society.
Figure 15
René
Magritte’s Elective Affinities (1933), oil
on canvas (41 cm × 33 cm). Private collection.
Public domain image; source: https://www.renemagritte.org/elective-affinities.jsp.
Rpan class="Chemical">enn>é
Magritte’s Elective Affinities (1933), oil
on canvas (41 cm × 33 cm). pan class="Chemical">Private collection.
pan class="Chemical">Public domain image; source: https://www.renemagritte.org/elective-affinities.jsp.
Fortunately, in chemistry, things
are differpan class="Chemical">ent: synthesizing a
molepan class="Chemical">cular cage and confining in it a chemical species (a metal ion,
an anion, or a molecule) are considered a deserving and admirable
action. The design and synthesis of cages at a molecular level have
become so popular and distinguished, an activity mentioned in the
Merriam–Webster dictionary: “an arrangement of atoms
or molecules so bonded as to enclose a space in which another atom
or ion (as of a metal) can reside”.[27] However, the analogy between the cages of the macroscopic world
and those of the molecular world may not be fully justified. In fact,
a living being in a macroscopic cage stays under an unpleasant kinetic
control: it may have the greatest tendency to escape from the cage,
but this event is prevented by an insurmountable activation barrier
(dense metal bars and a firmly locked gate). On the molecular side,
such a kinetically controlled situation is rarely observed. We have
seen that as far as anions are concerned, no kinetic barrier exists
for getting in/out of a bistren cage: the host is no longer a prisoner,
and its stay in the cage is thermodynamically controlled.
A
second example of cages in figurative arts is provided by the
famous and intriguing wood-pan class="Chemical">engraved print by M. C. Escher (Stars, 1948, https://mcescher.com/lw-359/). The print depn>icts two n>an class="Species">chameleons confined in a cage composed of
three interlocking regular octahedra, floating through space. The
image illustrates the attempt of the universe to impose its immutable
and celestial order (represented by polyhedra) to the overwhelming
force of life (the two chameleons).
A chemical imitation of
Escher’s print is shown in Figure , illustrating
a variety of pan class="Chemical">anions caged by pan class="Chemical">bistren receptors. The artistic quality
of the picture is rather poor, but the drawn chemical cages remain
fascinating and promising objects, deserving attention and further
investigations in their basic and applicative aspects.
Figure 16
Chemical
imitation of Escher’s print “Stars”
illustrating a variety of anions caged by bistren receptors.
This image appears as the cover for the March 28, 2015 issue of Organic & Biomolecular Chemistry, (Volume 13, Number
12) to accompany an article by the author. Adapted from Fabbrizzi et al. (2015).
Copyright 2015 Royal Society of Chemistry.
Chemical
imitation of Escher’s print “Stars”
illustrating a variety of pan class="Chemical">anions caged by pan class="Chemical">bistren receptors.
This image appears as the cover for the March 28, 2015 issue of Organic & Biomolecular Chemistry, (Volume 13, Number
12) to accompany an article by the author. Adapted from Fabbrizzi et al. (2015).
Copyright 2015 Royal Society of Chemistry.
Schiff Base Condensations
Driven by Metal Ions:
Rings and Macrocycles
Transition pan class="Chemical">metal ions can address pan class="Chemical">Schiff
base condensations to
sophisticated shapes acting as templates. An example is provided by
the self-reaction of o-aminobenzaldehyde, illustrated
in Figure .
Figure 17
Schiff base
self-condensation of o-aminobenzaldehyde
in the absence (route (i)) and in the presence of a nickel(II) salt
(route (ii)). The NiII ion acts as a square template and
drives the condensation to the formation of a tetra-aza macrocycle.[30]
pan class="Chemical">Schiff basen>
selpan class="Chemical">f-condpan class="Chemical">ensation of o-aminobenzaldehyde
in the absence (route (i)) and in the presence of a nickel(II) salt
(route (ii)). The NiII ion acts as a square template and
drives the condensation to the formation of a tetra-aza macrocycle.[30]
The pan class="Chemical">amine group and
the n>an class="Chemical">aldehyde group of the same molecule are
sterically prevented to give intramolecular Schiff base condensation.
Thus, head–tail intermolecular reactions take place to give
a linear polymer in the form of a sticky yellow product, route (i)
in Figure . On the
other hand, if nickel(II) perchlorate is added to a refluxing ethanolic
solution of o-benzaldehyde in the stoichiometric
ratio 1:4, a red crystalline precipitate forms, consisting of the
perchlorate salt of a NiII complex (18) of
a tetra-aza macrocycle named TAAB (acronym of TetrA-Amino-Benzaldehyde), route (ii)
in Figure .[28] Formation of the macrocycle is driven by NiII, which, as a d8 cation, favors square coordination
and addresses Schiff base condensation in such a way to be coordinated
by four iminenitrogen atoms positioned at the corners of a square.
Thus, NiII behaves as a square template. The [NiII(TAAB)]2+ complex is exceptionally stable, suffering no
decomposition in boiling concentrated HNO3, HCl, and HClO4. Hydrolysis of the imine bond is prevented by the closed
structure of the macrocycle and by the protective effect of the coordination.
The same template effect is exerted by CuII, which shows
a marked preference toward tetragonal coordination and may act as
a square template. Under the previously described conditions, a dark
green microcrystalline product is obtained, [CuII(TAAB)](NO3)2.
The structural formula of TAAB is highly
symmetric and reminiscpan class="Chemical">ent
of that of pan class="Chemical">porphyrin. The FeII complex of porphyrin (heme)
is an essential part of metalloproteins, in charge of fundamental
functions (transport and storage of dioxygen, electron transfer in
membranes, and elsewhere). The formula of synthetic porphyrin whose
iron(II) complexes reversibly with dioxygen is shown in Figure (19).
Figure 18
Synthetic porphyrin (19). (a) Crystal structure of
the FeII complex with porphyrin 19,[29] from which 2-((tert-butyrylamino)amino)phenyl
substituents have been removed (top view). (b) Crystal structure of
the oxygenated form of complex 19, which has to be considered
a complex of FeIII, to which a superoxide ion (O2–) is axially coordinated according to a side-on
bonding mode (FeIII–O–O angle = 130°)
and the other axial position is occupied by 1-ethyl-imidazole.[31]
Synthetic pan class="Chemical">porphyrin (19). (a) Crystal structure of
the FeII complex with n>an class="Chemical">porphyrin 19,[29] from which 2-((tert-butyrylamino)amino)phenyl
substituents have been removed (top view). (b) Crystal structure of
the oxygenated form of complex 19, which has to be considered
a complex of FeIII, to which a superoxide ion (O2–) is axially coordinated according to a side-on
bonding mode (FeIII–O–O angle = 130°)
and the other axial position is occupied by 1-ethyl-imidazole.[31]
Figure a shows
the crystal structure of the FeII complex of synthetic
pan class="Chemical">porphyrin without 2-pan class="Chemical">((tert-butyrylamino)amino)phenyl
substituents.[29]Figure b displays the oxygenated form of the same
complex. On oxygenation, one electron is transferred from FeII to O2, and the product should be considered an FeIII–O2– adduct. Extended
delocalization of π electrons makes the porphyrinato ring almost
perfectly planar. Such an aesthetically agreeable molecule is a sophisticated
product of natural evolution dating back to 4 billion years.
The crystal structure of the [NiII(TAAB)]2+ complex is not as nice and an class="Chemical">ppealing (Figure ).[30]
Figure 19
Crystal structure
of the complex salt [NiII(TAAB)(MeCN)2](I3)2[30] (hydrogen
atoms, metal-coordinated MeCN molecules, and I3– counterions have been omitted for clarity). (a) Top view. (b) Lateral
view.
Crystal structure
of the pan class="Chemical">complex saltn> [pan class="Disease">NiII(TAAB)(MeCN)2](I3)2[30] (pan class="Chemical">hydrogen
atoms, metal-coordinated MeCN molecules, and I3– counterions have been omitted for clarity). (a) Top view. (b) Lateral
view.
The arrangempan class="Chemical">ent of a TAAB macrocycle
is anything but planar, a
behavior ascribed to the absn>an class="Chemical">ence of π-delocalization. In particular,
the ligand adopts a saddle conformation. The old saying goes “don’t
put the saddle before the horse”. This is what cultural evolution
pretentiously did by synthesizing [NiII(TAAB)]2+, but it failed miserably the competition with the more patient and
wise natural evolution.
Tetrahedral Container for
a Tetrahedral Molecule,
P4
pan class="Chemical">Metal template n>an class="Chemical">Schiff base condensations may give rise
to more
sophisticated and aesthetically agreeable shapes than the uneven square
described in the previous section. A good example is provided by a
tetrahedron. Nitschke et al. synthesized a tetrahedral molecular system
through a metal template Schiff base condensation process, as illustrated
in Figure .[31]
Figure 20
One-pot template synthesis of tetrahedral molecular system 23.[33] The process can be ideally
divided into two separate steps: (i) Schiff base condensation of 12
mol of 2-formylpyridine (20) and of 4,4′-diaminobiphenyl-2,2′-disulfonate
(21) to give 22 and (ii) binding of three
imino-pyridine fragments from three distinct molecules of 22 to FeII according to an octahedral coordination geometry,
which gives tetrahedrally shaped molecule 23. Adapted from ref (31). Copyright 2008 Wiley–VCH
Verlag GmbH & Co. KGaA.
One-pot template synthesis of tetrahedral molepan class="Chemical">cular system 23.[33] The process can be ideally
divided into two sepclass="Chemical">n>arate steps: (i) n>an class="Chemical">Schiff base condensation of 12
mol of 2-formylpyridine (20) and of 4,4′-diaminobiphenyl-2,2′-disulfonate
(21) to give 22 and (ii) binding of three
imino-pyridine fragments from three distinct molecules of 22 to FeII according to an octahedral coordination geometry,
which gives tetrahedrally shaped molecule 23. Adapted from ref (31). Copyright 2008 Wiley–VCH
Verlag GmbH & Co. KGaA.
The synthesis, which proceeds according to a one-pot mode in aqueous
solution at 50 °C, is split for clarity in Figure in two consepan class="Chemical">cutive equilibria:
(i) Schiff base condensation of 12 mol of aldehyde 20 with 6 mol of dianiline 21 to give 6 mol of linear
di-imine 22. Each molecule of 22 contains
at its ends two bidentate units N∩N, each one possessing one
sp2 pyridinenitrogen atom and one sp2 iminenitrogen atom. Indeed, FeII (d6 electronic configuration)
has been chosen as a templating ion because it shows a marked affinity
toward sp2 nitrogen atoms, to give a six-coordinated complex
of octahedral geometry (formula 24 in Figure ). The only way for making
FeII coordinated by three N^N subunits is that the six
molecules of 22 position themselves along the six edges
of a tetrahedron whose four vertices are occupied by FeII ions. This gives rise to tetrahedral molecular system 23. The driving force of the process is the formation of four [FeII(N∩N)3]2+ complex subunits made
stable by N (sp2)–FeII (d6 low-spin) coordinative interactions, both σ and π in
nature. Moreover, the intrinsic inertness of the [FeII(N∩N)3]2+ subunit imparts kinetic stability. System 23 is an anion of charge 4⊖, which results from the
balance of the 8⊕ charge of the 4 FeII ions and
the 12⊖ charge of the 12 sulfonate groups, [FeII4L6]4– (L = 22), and was isolated as a dark red methylammonium salt. On recrystallization
from water/acetone, dark red crystals of a diamagnetic salt of formula
(MeNH3)4[FeII4L6]·(CH3)2CO·H2O (L = 22) suitable for X-ray diffraction studies were obtained.
Tetramethyammonium was present because disulfonate 21 had been obtained in situ by neutralization of the corresponding
disulfonic acid with tetramethylammonium hydroxide. The crystal structure
of the complex anion is shown in Figure .[31]
Figure 21
(a) Crystal
structure of the salt (Me4N)4[FeII4L6]·(CH3)2CO·H2O (L = 22).[31] Covalently
linked sulfonate groups, hydrogen atoms, methylammonium
ions, and solvating water molecules are omitted for clarity. An acetone
molecule is well included in the tetrahedral receptor. (b) Sketch
of the tetrahedron whose vertices are occupied by FeII ions. Adapted from ref (31). Copyright 2008 Wiley–VCH
Verlag GmbH & Co. KGaA.
(a) Crystal
structure of the pan class="Chemical">salt (Me4N)4[FeII4L6]·(CH3)2CO·pan class="Chemical">H2O (L = 22).[31] Covalently
linked sulfonate groups, hydrogen atoms, methylammonium
ions, and solvating water molecules are omitted for clarity. An acetone
molecule is well included in the tetrahedral receptor. (b) Sketch
of the tetrahedron whose vertices are occupied by FeII ions. Adapted from ref (31). Copyright 2008 Wiley–VCH
Verlag GmbH & Co. KGaA.
The pan class="Chemical">[FeII4L6]4– complex (L = 22) shows a regular tetrahedral geometry.
The edge of the tetrahedron (FeII···FeII distance) is 12.9 Å, from which a volume of 251 Å3 can be caln>an class="Chemical">culated. Such a value corresponds very roughly
to the volume of the cavity. In Figure a, the 12 sulfonate groups covalently linked
to the diphenyl spacers in 2,2′- positions are not shown for
clarity. In any case, they point outward, which accounts for the solubility
of the complex salt in water. However, in accordance with the Aristotelian
principle (Natura abhorret vacuum), the tetrahedral cavity is not
void but contains a molecule of acetone, which has been probably incorporated
during the recrystallization process (diffusion of acetone on an aqueous
solution of the salt).
Figure 23
(a) “Libation vase of Gudea”
dedicated to the Sumerian
deity Ningišzida, the god of nature and fertility (the two
snakes, male and female), coiling around an axial rod as a double
helix, depict the god himself). Source: http://1886.u-bordeaux-montaigne.fr/items/viewer/76267#page/n1/mode/1up. (b) Caduceus, the short wand of Hermes (Mercury). (c) Alchemic
symbol of mercury (metal), a stylized caduceus. (d) Two stylized snakes
of a caduceus entwined in a double helix. Adapted from de Sarzec and Heuzey (1884).
Copyright 1884 E. Leroux.
The pan class="Chemical">[FeII4L6]4– complex can include other molen>an class="Chemical">cules
of appropriate size, e.g., P4, white phosphorus, which
has a tetrahedral shape.[32] White phosphorus
is a waxy solid, soluble in
apolar solvents (e.g., benzene) and insoluble in water. The sterically
constrained arrangement precludes a full overlap of σ orbitals,
which accounts for the formation of weak P–P bonds and for
the extreme reactivity of P4. White phosphorus is violently
pyrophoric in air with formation of P4O10 and
is kept under water to avoid any contact with oxygen. When an aqueous
solution of the [FeII4L6]4– complex is left in contact with white phosphorus, P4 is
incorporated into the tetrahedral receptor. The crystal structure
of the inclusion complex, isolated as a tetramethylammonium salt,
is shown in Figure .[32]
Figure 22
(a) Crystal structure of the salt (Me4N)4[FeII4L6]·P4 hydrate
(L = 22).[32] Covalently linked
sulfonate groups, hydrogen atoms, tetramethylammonium ions, and solvating
water molecules are omitted for clarity. A tetraphosphorus molecule
is well included in the tetrahedral receptor. (b) Sketch of the tetrahedron
whose vertices are occupied by FeII ions. Adapted from ref (32). Copyright 2009 American
Association for the Advancement of Science.
(a) Crystal structure of the pan class="Chemical">salt (Me4N)4[FeII4L6]·pan class="Chemical">P4 hydrate
(L = 22).[32] Covalently linked
sulfonate groups, hydrogen atoms, tetramethylammonium ions, and solvating
water molecules are omitted for clarity. A tetraphosphorus molecule
is well included in the tetrahedral receptor. (b) Sketch of the tetrahedron
whose vertices are occupied by FeII ions. Adapted from ref (32). Copyright 2009 American
Association for the Advancement of Science.
The pan class="Chemical">P4 molepan class="Chemical">cule is well included
in the cavity and is
stabilized by the van der Waals interactions betweenphosphorus atoms
and the aromatic rings decorating the interior of the cavity. When
trapped in the cage, both in aqueous solution and in the solid phase,
it is insensitive to dioxygen and remains indefinitely unchanged in
air. The lack of reactivity of P4 does not derive from
a mechanical protection exerted by the cage but by the circumstance
that the reaction of O2 with P4 would necessarily
generate a preliminary P=O fragment too large for the cavity.
It is intriguing that the tetrahedral [FeII4L6]4– complex is the receptor of choice
of smaller tetrahedral molecule P4, which suggests the
existence of a principle of geometrical correspondence (like includes
like). However, if an aqueous layer containing the {[FeII4L6]·P4}4– inclusion complex is equilibrated (vigorously shaken) with a benzene
layer, P4 moves to the organic layer and is replaced in
the cavity by a benzene molecule. Benzene has a shape quite different
from a tetrahedron, but it can establish quite strong π–π
interactions with the aromatic moieties coating the cavity’s
walls, distinctly stronger than the vdW interactions established by
P4.
An Icon of Human Image: The
Double Helix
Objects arranged in a double-strand helical
shape have attracted
and intrigued pan class="Species">human beings for a long time.[33] The first known example refers to a grepan class="Chemical">en steatite libation vase
exhipan class="Chemical">bited in the Louvre featuring the Sumerian deity Ningišzida
(see Figure a).
(a) “Libation vase of Gudea”
dedicated to the Sumerian
deity Ningišzida, the god of nature and fertility (the two
snakes, male and female), coiling around an axial rod as a double
helix, depict the god himself). Source: http://1886.u-bordeaux-montaigne.fr/items/viewer/76267#page/n1/mode/1up. (b) Caduceus, the short wand of Hermes (pan class="Chemical">Mercury). (c) Alchemic
symbol of n>an class="Chemical">mercury (metal), a stylized caduceus. (d) Two stylized snakes
of a caduceus entwined in a double helix. Adapted from de Sarzec and Heuzey (1884).
Copyright 1884 E. Leroux.
Gudea,
the ruler of the city and state of Lagash in Southern Mesopotamia
during the period 2144–2124 BC, dedicated this vase to Ningišzida,
the god of fertility, represpan class="Chemical">ented as a pair of snakes wound around
a woodn>an class="Chemical">en wand or a scepter. The two snakes (male and female) face
each other with open mouths at the top of the staff, while at its
base their tails interlace, a clear allusion to the reproductive intercourse.
The theme of a staff with two snakes intertwined around it was later
adopted by Greek mythology. In fact, the caduceus, a short wand entwined
by two serpents with surmounting wings, is typically carried out by
god Hermes (later the Latin god Mercury, shown in Figure b). It is believed that Hermes
was an Oriental deity of Babylonian extraction, later accepted with
a subsidiary role in the Olympian Pantheon. Mercury played other two
significant roles in humanculture: (i) as one of the seven planets
of the geocentric system and (ii) as one of the sevenmetals of Alchemy.
A stylized drawing of the caduceus (Figure c) represented the symbol of mercury both
in astronomy and alchemy. Figure d highlights the intertwining of the two snakes in
a double helix mode in the symbol.
The double helix has also
represpan class="Chemical">ented an ampan class="Chemical">bitious task in architecture:
a spectacular example is provided by Saint Patrick’s well in
Orvieto, Italy, designed to obtain water from the depths of the bluff
where the city of Orvieto sits (Figure ). It was constructed by Antonio da Sangallo
the Younger, the most visionary architect-engineer in Italy at that
time, during the period 1527–1537. The well is 53 m deep and
14 m wide and is equipped with a pair of wide spiral staircases each
made of 298 stairs, lit by 72 internal windows, which forms a double
helix, so that mules laden with water jars could descend on one ramp
and come back up the other, without colliding.
Figure 24
Well of Saint Patrick,
Orvieto, Italy, built by the Florentine
architect Antonio da Sangallo the Younger (1527–1537), under
the stimulus by Pope Clemente VII, to serve as a water supply in the
case of siege. (a) Top view. (b) View of the stairs of one helix [images
courtesy of Bellaumbria.net].
Well of Saint pan class="Chemical">Patrick,
Orvieto, Italy, built by the Florpan class="Chemical">entine
architect Antonio da Sangallo the Younger (1527–1537), under
the stimulus by Pope Clemente VII, to serve as a water supply in the
case of siege. (a) Top view. (b) View of the stairs of one helix [images
courtesy of Bellaumbria.net].
In 1953, double helices pan class="Chemical">entered
astonishingly the world of scipan class="Chemical">ence
with the disclosure by Crick and Watson of the structure of DNA, a
discovery that has dramatically changed the way mankind thinks about
life sciences.[34] In chemistry, the double
helix has become since then a recurring motif of inspiration for molecular
design and syntheses. In 1987, Lehn et al. reported the first example
of inorganic double helices, i.e., a series of polynuclear metal complexes
(helicates), in which two linear multidentate ligands are coiled around
two or more metals forming a double helix.[35] Both DNA and helicates are held together by labile non-covalent
interactions (hydrogen bonding and metal–ligand, respectively),
a feature that allows the fast and reversible molecular assembling
to give an elaborate structure, through a repetitive trial-and-error
mechanism. The double helical structure of helicate complexes results
from the fine balance between (i) the geometrical preferences of the
metal center for coordination and (ii) the steric constraints imposed
by the linear ligand, which may contrast the formation of a mononuclear
complex. Mononuclear tetrahedral complexes already possess a helical
twist and are good candidates for the formation of helicates. In fact,
the first double-stranded helicates were obtained with d10 metal ions (CuI and AgI), which have a strong
preference for a tetrahedral coordination geometry.
pan class="Chemical">Polypyridine 25 contains three 2,2′-pan class="Chemical">bipyridine
subunits (N∩N), each one capable to act as a bidentate ligand.
On adding a CH2Cl2 solution of 25 to an MeCN solution of AgCF3SO3, a white precipitate
of [AgI3L2](CF3SO3)3 forms. In particular, 3 AgI ions
and 2 molecules of 25 self-assemble to give trinuclear
complexes in which the two polypyridine strands are intertwined around
the metal ions in a double helix mode. The driving force of the process
is the energy associated to the formation of a tetrahedral [AgI(N∩N)2]+ complex (Figure a). The −CH2–O–CH2– bridge linking 2,2′-bipyridine
units of 25 is too short to permit tetrahedral binding
of an ion by two N∩N units of the same ligand molecule, and
it is flexible enough to allow strain-free coordination in a dimeric
fashion. As a consequence, the double-stranded helicate complex [AgI3L2]3+ forms, whose crystal
structure is shown in Figure b.[36] On replacing AgCF3SO3 with [CuI(MeCN)4]ClO4, under the same conditions, a red-orange salt precipitates of formula
[CuI3L2](ClO4)3, which contains a double-stranded helicate complex with a structure
similar to that shown in Figure b.
Figure 25
Tris-bidentate ligand containing three 2,2′-bipyridine
subunits
(helicands), 25. (a) Metal ion that prefers tetrahedral
coordination (d10 electronic configuration, e.g., AgI), thus possessing a helical twist. (b) Crystal structure
of the double-stranded helicate complex [AgI3L2]3+ (L = 25).[36] White spheres represent AgI ions. The two strands
have different colors to evidence the double-helix arrangement. Triflate
counterions have been omitted for clarity.
pan class="Chemical">Tris-pan class="Chemical">bidentate ligand containing three 2,2′-bipyridine
subunits
(helicands), 25. (a) Metal ion that prefers tetrahedral
coordination (d10 electronic configuration, e.g., AgI), thus possessing a helical twist. (b) Crystal structure
of the double-stranded helicate complex [AgI3L2]3+ (L = 25).[36] White spheres represent AgI ions. The two strands
have different colors to evidence the double-helix arrangement. Triflate
counterions have been omitted for clarity.
Not unexpectedly, pan class="Chemical">CuI can address pan class="Chemical">Schiff base condensation
of primary amines and carbonyl derivatives toward the formation of
multinuclear double-stranded helicates, provided that (i) the helicand
possesses sp2 nitrogen atoms (imines and pyridines), to
favor back donation from a filled dπ orbital of the metal to
an empty π* molecular orbital of the ligand, and (ii) reacting
fragments are equipped with bulky substituents disfavoring the formation
of mononuclear complexes.
A good example is illustrated in Figure . pan class="Chemical">Schiff base condpan class="Chemical">ensation
of 1 mol of diketone 26 with 2 mol of amine 27 gives imine derivative 28, which contains four bidentate
subunits N∩N and
may act as a helicand. Then, 2 mol of 28 and 4 mol of
CuI assemble to give the double-stranded tetranuclear helicate
complex [CuI4L2]4+ (L
= 28), whose crystal structure is shown in Figure a. The four CuI ions are positioned along the axis of the helices, each one
profiting from a flattened tetrahedral coordination. The four bulky n-butyl substituents at the end of the strands as well as
the four ketamine groups prevent the formation of mononuclear species
and favor the double helical arrangement.[37]
Figure 26
Schiff base metal template synthesis of a tetracopper(I) double-stranded
helicate. (a) Crystal structure of the complex salt [CuI4L2](CuI2I4)2, L = 25(37) (hydrogen
atoms and counteranions have been omitted for clarity). (b) Same structure
as a but with one strand yellow and the other green.
pan class="Chemical">Schiff basen> pan class="Chemical">metal template synthesis of a tetrapan class="Chemical">copper(I) double-stranded
helicate. (a) Crystal structure of the complex salt [CuI4L2](CuI2I4)2, L = 25(37) (hydrogen
atoms and counteranions have been omitted for clarity). (b) Same structure
as a but with one strand yellow and the other green.
A helix possesses its own chirality deppan class="Chemical">ending whether it
is right-handed
(n>an class="Chemical">P) or left-handed (M). Any double
helicate is a racemic mixture of the two enantiomers P,P and M,M, which
are both present in the elementary cell. For instance, both the structures
reported in Figure b, [AgI3L2]3+, and in Figure , [CuI4L2]4+, refer to P,Penantiomers.
An intriguing complication
ocpan class="Chemical">curs whpan class="Chemical">en one of the reagents of the
Schiff base condensation possesses its own chirality. This is the
case of the reaction of trans-1,2-cyclohexanediamine
(racemic mixture) with 2-pyridine-carbaldehyde and its derivatives
in the presence of the CuI template, illustrated in Figure .[38]
Figure 27
Template synthesis of the double-stranded helicate complex
[CuI2L2]2+ (L = 29). On reaction of rac-1,2-cyclohexanediamine with isoquinolyl
aldehyde,
a racemic mixture of the complex was obtained consisting of the two
enantiomers M,M-[CuI2(L)2]2+ and P,P-[CuI2(L)2]2+ in a
1:1 ratio.[38]
Template synthesis of the double-stranded helicate complex
pan class="Chemical">[CuI2L2]2+ (L = 29). On reaction of n>an class="Gene">rac-1,2-cyclohexanediamine with isoquinolyl
aldehyde,
a racemic mixture of the complex was obtained consisting of the two
enantiomers M,M-[CuI2(L)2]2+ and P,P-[CuI2(L)2]2+ in a
1:1 ratio.[38]
As the helicand 29 (= L) is constituted by two pan class="Chemical">enantiomers, L and L, a further elempan class="Chemical">ent of complexity is introduced:
the matching of the chiral properties of one strand with the other
when the dicopper(I) helicate complex forms. In particular, on reaction
of equimolar amounts of L with a CuI salt, one would expect, on a pure statistical basis, the
formation of a mixture of products made with 50% “scrambled”
double helicate [CuI2(L)(L]2+, with 25% [CuI2(L)2]2+, and with 25% [CuI2(L)2]2+. However, the formation of
a racemic mixture of homochiral dinuclear species was observed: 50% M,M-[CuI2(L)2]2+ (i.e., two intertwined
helices, both with M handedness) and 50% P,P-[CuI2(L)2]2+ (i.e., two intertwined
helices, both with P handedness) in the unit cell.
The structures of the two enantiomers are shown in Figure .
Thus, in the formation
of the double helicate complex, strands
of the same chirality seek each other, thus obeying the principle
of homochiral recognition.[38,39] The selpan class="Chemical">f-recognition
process is described by equilipan class="Chemical">brium (eq )
The ocpan class="Chemical">cun>rrpan class="Chemical">ence of homochiral recognition has bepan class="Chemical">en ascribed
to the
fact that two rigid units of the same chirality combine to give a
compact structure, whereas two heterochiral units give a less compact
structure.[39]
Borromean
Rings
Borromean Rings (pan class="Chemical">BRs) are a topological object constituted
by three
circles: all together are bound and insepn>arable, but takn>an class="Chemical">en two by
two, they are not. This basically means that if one were to cut or
take away one ring, then the other two would fall apart. As such,
BRs, since the early times, pictorially represented “strength
in unity” and have been chosen as a symbol by several cultures
and religions. As an example (see Figure a), in the Catholic religion, BRs represent
Holy Trinity (one God in three Divine persons).
Figure 28
(a) Borromean rings
as a symbol of the Christian Trinity, based
on an illustration in a 13th-century French manuscript found at Chartres.
Source: http://1886.u-bordeaux-montaigne.fr/items/viewer/76267#page/n4/mode/1up. (b) Bronze medal of unknown origin, featuring on one side Cosimo
de’ Medici the Elder and on the other side the three interlocked
rings, at that time the family crest. (c) Symbol of Cardinal St. Charles
Borromeo (1538–1584), a prominent member of the Borromeo family
(image courtesy of Seminario Arcivescovile di Milano).
(a) Borromean rings
as a symbol of the Christian Trinity, based
on an illustration in a 13th-cpan class="Chemical">entury Frpan class="Chemical">ench manuscript found at Chartres.
Source: http://1886.u-bordeaux-montaigne.fr/items/viewer/76267#page/n4/mode/1up. (b) pan class="Chemical">Bronze medal of unknown origin, featuring on one side Cosimo
de’ Medici the Elder and on the other side the three interlocked
rings, at that time the family crest. (c) Symbol of Cardinal St. Charles
Borromeo (1538–1584), a prominent member of the Borromeo family
(image courtesy of Seminario Arcivescovile di Milano).
The Medici in Florpan class="Chemical">ence adopted the three intertwined rings
as family
coat of arms as shown for instance by the bronze medal featuring on
one side Cosimo the Elder (1389–1464), the first member of
the Medici family that de facto ruled Florence and on the other side
the three rings (see Figure b). However, the most clear and appealing demonstration of
the connection betweenBRs and Medici is provided by the painting
by Sandro Botticelli shown in Figure .
Figure 29
Sandro Botticelli’s (1445–1510) Pallas and
the Centaur (ca. 1482), tempera on canvas, 207 × 148
cm, in the Uffizi Gallery, Florence. (a) Detail showing four intertwined
rings. (b) Detail showing Borromean rings.
Sandro Botticelli’s (1445–1510) pan class="Chemical">Pn>allas and
the Cpan class="Chemical">entaur (ca. 1482), tempera on canvas, 207 × 148
cm, in the Uffizi Gallery, Florpan class="Chemical">ence. (a) Detail showing four intertwined
rings. (b) Detail showing Borromean rings.
The painting illustrates a subject of ancipan class="Chemical">ent Greek mythology:
pan class="Chemical">Pallas, the goddess of wisdom, clutches the hair of a centaur, and
he seems submissive to her. Centaurs were typically associated with
uncontrolled passion and sensuality. Thus, a first level allegory
of the painting refers to the primacy of reason over passion. However,
there exists a more elaborate meaning related to the political events
involving the Florentine Republic and the Medici family at the end
of the 15th century.
In 1478, pan class="Chemical">Pope Sixtus IV formed a military
alliance with King Ferdinand
I of Napn>les, their armies invaded Tuscany, and in November 1479, they
ocn>an class="Chemical">cupied Colle Val d’Elsa, a fortified town 80 km from Florence.
The Florentine Republic was in serious danger, and its ruler Lorenzo
de’ Medici, the Magnificent, traveled by sea to Naples to have
direct talks with the King of Naples. Lorenzo was received at the
court with full honors and remained in Naples as a respected guest
for three months. Lorenzo impressed Ferdinand with his culture and
savoir faire and ultimately convinced him to withdraw troops from
Tuscany, thus ending the war. This diplomatic success highly increased
in Italy and abroad the reputation of Lorenzo, who pursued a policy
of maintaining peace, balancing power between Italian states, and
keeping major European states such as France and the Holy Roman Empire
out of Italy. Later, Medici left the three interlaced ring and took
as a family crest the shield with six balls (in origin bezants, the
gold coins used in the Byzantine Empire, to emphasize the main family
business: banking).
Botticelli’s painting allegorically
illustrates the diplomatic
success by Lorpan class="Chemical">enzo: the Florentine Republic, personified by Pallas,
with the force of reason but also with the threat of weapons (represented
by the halberd), dominates and tames the centaur, which represents
the Kingdom of Naples. It is allusive of Naples the gulf in the background.
The role of Medici is subtly and elegantly suggested by Pallas’
clothing, which is decorated by a variety of Borromean rings (Figure , inset b). The
decoration was probably suggested to the painter by Lorenzo himself
or by a complacent member of the Neoplatonic Circle, led by the philosopher
Marsilio Ficino and the poet Agnolo Poliziano. Sandro Botticelli respectfully
accepted the suggestion, but as a renowned kidder, he also put on
the clothing groups of four intertwined twins, which are neither insignia
nor a topological figure (Figure , inset b). Lorenzo and his followers took the hint
but did not object.
At this stage, one could ask why we pan class="Chemical">currpan class="Chemical">ently
speak of Borromean
rings and not of Medicean rings. The Borromeo family was running during
the 15th century an inn in San Miniato al Tedesco, a village between
Florence and Pisa, positioned along the Via Francigena, the pilgrim
route running from France to Rome. Thus, the inn offered accommodation
to the numerous pilgrims going to Rome (a pilgrim to Rome was called
Romeo) from all of Europe. The inn was therefore entitled to “Bon
Romeo” (the good pilgrim to Rome), from which the hoteliers
took their surname, Borromeo. Religious tourism at that time was a
big business. The Borromeo family made money enough to open a bank
in Florence. They had success and opened branches in towns of Northern
Italy, including Milan. Here, they found a prestigious customer, the
Dukes of Lombardy, Visconti and later Sforza. These families were
continuously involved in wars against the neighboring states, and
in the years, they borrowed from the Borromeo bank an enormous amount
of money. To service the debt, Francesco I Sforza gave to the Borromeos
lands and castles in Western Lombardy, around the Lago Maggiore, and
granted them the count title. At this stage, the Borromeo family was
looking for a coat of arms and chose the three rings, which they had
seen in Florence and which had been dismissed by Medici. Figure c shows the emblem
of one of the most important members of the family, Cardinal St. Carlo
Borromeo (1538–1584), which is still the symbol of active institutions
founded by the cardinal: the Almo Collegio Borromeo in Pavia (1561)
and the Archiepiscopal Seminary of Milan (1564). The word “humilitas”
in the crest is taken by St. Augustine’s Latin phrase “Humilitas
occidit superbiam” (humility kills pride), which refers to
the victorious fight of David against the giant Goliath.
On
the chemical side, pan class="Chemical">BRs represented an ambitious challenge for
many researchers. Classical organic synthetic procedures, made by
a sequence of irreversible and kinetically controlled steps, did not
produce any result. In the first years of the third millennium, Fraser
Stoddart, a Scottish chemist, at that time a professor at UCLA, who
in 2016 would have shared the Nobel Prize in Chemistry with Jean-Pierre
Sauvage and Ben Feringa for molecular machines, adopted a metal template
approach based on Schiff base condensation. The one-pot process was
successful and is illustrated in Figure .[40]
Figure 30
Stoddart’s
template synthesis of Borromean rings.[40] The one-pot synthesis was carried out in refluxing
MeOH (3 h) in the presence of Zn(CF3COO)2. The
hexametallic complex (32) is depicted in an orthogonal
representation.
Stoddart’s
template synthesis of Borromean rings.[40] The one-pot synthesis was carried out in refluxing
pan class="Chemical">MeOH (3 h) in the prespan class="Chemical">ence of Zn(CF3COO)2. The
hexametallic complex (32) is depicted in an orthogonal
representation.
The synthesis involves
6 mol of pan class="Chemical">diformylpyridine, 6 mol of a primary
n>an class="Chemical">diamine (30) containing 2,2′-bipyridine (bpy)
subunits, and 6 mol of Zn2+ (dissolved as trifluoroacetate).
ZnII was chosen for its affinity toward five-coordination
and was expected to bind the bidentate subunit bpy (N∩N) and
the tridentate subunit (N^N^N), resulting from the condensation of
diformylpyridine with the primary amine groups of two distinct molecules
of 30. (2 + 2) Schiff base condensation of diformylpyridine
and 30 leads to the formation of three macrocycles (31). The three macrocycles, in order to ensure the formation
of six [Zn(N∩N)(N^N^N)]2+ complex subunits, interlock
themselves according to the orthogonal representation of the Borromean
rings. The [ZnII6L3]12+ hexanuclear complex forms under a thermodynamic control, and its
stability results from the enthalpic contributions from the formation
of 30 ZnII–N bonds and, to a lesser extent, from
the establishing of π–π interactions between aromatic
rings. The reversibility of the C=N bonds and the trial-and-error
mechanism allowed the achievement, in 3 h in refluxing MeOH, of a
so complex and sophisticated structure. The key move of the successful
game was to make the bidentate subunits N∩N point outward the
macrocycle and the tridentate units N^N^N inward.
Figure c shows
the crystal and molepan class="Chemical">cular structure of the pan class="Chemical">[ZnII6L3](CF3COO)12 (L = 31) complex salt.[42] Taking inspiration from
the nomenclature introduced by Lehn (cryptand/cryptate),[18] the system of the three ligating macrocycles
(31), is called borromeand (a ligand capable to give
metal complexes in the form of Borromean rings) and the corresponding
complex [ZnII6L3]12+ borromeate.
It has to be noted that the complex appears in the orthogonal structure
(Figure b) and not
in the more familiar topologically equivalent planar structure in Figure a. In Figure d, the orthogonal
graph has been superimposed on the crystal structure of the borromeate
complex.
Figure 31
Crystal structure of the borromeate complex salt [ZnII6L3](CF3COO)6 (L = 31).[40] (a) Classical flat representation
of Borromean rings. (b) Orthogonal representation (structures a and b courtesy of Mathcurve, https://mathcurve.com. (c) Crystal
structure of the borromeate complex (hydrogen atoms and trifluoroacetate
counterions have been omitted for clarity). (d) Same structure on
which the orthogonal graph has been superimposed.
Figure 32
(a)
Ugo Schiff delivering his last lecture (Lectio Magistralis) on Saturday April 24, 1915, in the amphitheater of the Institute
of Chemistry at the University of Florence. (b) Front wall of the
amphitheater today on refurbishment (courtesy of the Università
di Firenze) (over the blackboard, there are the portraits in relief
of Jakob Berzelius (1779–1848), left, and of Humphry Davy (1778–1829),
right, and the Ancient Greek inscription ΠANTA METPΩ KAI
APIΘMΩ KAI ΣTAΘMΩ (all things by measure
and number and weight)).
Crystal structure of the pan class="Chemical">borromeate pan class="Chemical">complex salt [ZnII6L3](CF3COO)6 (L = 31).[40] (a) Classical flat representation
of Borromean rings. (b) Orthogonal representation (structures a and b courtesy of Mathcurve, https://mathcurve.com. (c) Crystal
structure of the borromeate complex (hydrogen atoms and trifluoroacetate
counterions have been omitted for clarity). (d) Same structure on
which the orthogonal graph has been superimposed.
(a)
pan class="Chemical">Ugo pan class="Chemical">Schiff delivering his last lecture (Lectio Magistralis) on Saturday April 24, 1915, in the amphitheater of the Institute
of Chemistry at the University of Florence. (b) Front wall of the
amphitheater today on refurbishment (courtesy of the Università
di Firenze) (over the blackboard, there are the portraits in relief
of Jakob Berzelius (1779–1848), left, and of Humphry Davy (1778–1829),
right, and the Ancient Greek inscription ΠANTA METPΩ KAI
APIΘMΩ KAI ΣTAΘMΩ (all things by measure
and number and weight)).
Noteworthy, despite
the complexity of the mechanism, the zinc(II)
pan class="Chemical">borromeate n>an class="Chemical">salt can be obtained in a multigram scale in an undergraduate
organic lab (average yield of 86%).[41] This
conclusively demonstrates the efficiency of Schiff base condensations
when addressed by metal ions of known geometrical preferences and
defines an emerging area in which synthetic organic, inorganic, and
coordination chemistry, supramolecular chemistry, and dynamic covalent
chemistry merge and cooperate.[42]
Professor Ugo Schiff: His Classroom and His
Students
In 1864, Carlo Matteucci, the Minister of pan class="Chemical">Public
Education of the
newly founded Italian State, called pan class="Gene">Hugo Schiff, a senior assistant
at the University of Pisa, to cover the Chair of Chemistry at the
Royal Institute for Practical and Advanced Studies in Florence, something
similar to a doctorate school. At that time, there was no university
in Florence. Indeed, a university had been founded in Florence as
a studium in 1231, but it had been closed in 1475, transferred and
merged with the University of Pisa by Lorenzo the Magnificent, a surprising
resolution by a unique patron of the arts, literature, and philosophy,
firmly determined to make Florence a leading center of culture in
Italy and in Europe. However, Lorenzo probably had realized that universities
and their students could represent a source of revolutionary ideas
and a menace to the established power, i.e., something to keep at
a reasonable distance (68 km in this particular case), a not odd choice
at the time, if one considers that Milan had its university in Pavia
(31 km), Venice in Padua (35 km), and London in Oxford (83 km) and
Cambridge (80 km). Schiff, the first professor of Chemistry at the
Royal Institute, found the laboratories of chemistry, hosted by the
Royal Museum of Physics and Natural History, small and inadequate.
He began a long fight to convince the minister to transfer Chemistry
in a suitable place, which was finally founded in a former religious
institute behind the Basilica of the Most Holy Annunciation, downtown.
Schiff participated actively with suggestions and blueprints drawn
by himself to the renovation of the old building and to its adjustment
to fulfill chemical requirements (1882–1885). In particular,
he personally designed the main amphitheater in which he used to have
classes, inspired by the chemical amphitheater of the University of
Göttingen, his alma mater. The chemical amphitheater in Florence
has been eternalized by a famous photograph showing Schiff that delivers
his last lecture (Lectio Magistralis), displayed
in Figure a.
Figure b shows
an inscription in ancipan class="Chemical">ent Greek set over the blackboard: ΠANTA
METpan class="Chemical">PΩ KAI APIΘMΩ KAI ΣTAΘMΩ—[You,
My God, have ordered] all things by measure and number and weight.
The sentence, an invocation by Solomon to God, taken from the Book
of Wisdom, Chapter 11, seems to describe the divine order of the physical
world and to suggest the scientific keys for studying and interpreting
nature. However, on reading the complete paragraph in the Book of
Wisdom, the meaning appears totally different and unrelated to science:
“Even without these [the Plagues of Egypt], they [the Egyptians]
could have been killed at a single breathe, pursued by justice and
winnowed by Your mighty spirit. But You, My God, ordered all things
by measure and number and weight.” Thus, Solomon praises the
clemency of God in softly punishing the Egyptians, guilty of persecuting
the Israelites. UgoSchiff, son of a Jewish family, very probably
knew the Book of Wisdom (even if this book is not accepted in the
Jewish Bible), mastered ancient Greek (as well as Latin and Hebrew,
plus German, Italian, and French), and was aware of the sense of Solomon’s
invocation. However, he was intrigued by the “scientific”
misinterpretation of the sentence and wanted it to perpetually admonish
students attending classes in the amphitheater (including the writer
of these notes). Significantly, the Latin version of the above sentence
(Omnia in mensura et numero et pondere) is present in the Aula Magna
of the Department of Chemistry at the University of Bologna. The Aula
was constructed following the will of Giacomo Ciamician (1857–1922).
Ciamician was a younger colleague and a friend of UgoSchiff and was
probably inspired by a visit to the chemical amphitheater in Florence.
pan class="Chemical">Schiff taught classes until 1915, the year of his pan class="Disease">death, aged 81.
The age limit for University professors at the time was 75, a restriction
from which he was exempted for his special scientific merit. He delivered
his last lecture (lectio magistralis) on April 24, 1915, the closest
Saturday to his 81st birthday (April 26). Schiff chose Saturday, at
the time a half working day, for not interfering with the teaching
schedule of students and colleagues (see the photograph in Figure a).
pan class="Chemical">Schiff
was an appreciated and passionate teacher, but he was also
a demanding examiner. Figure a reports a comment written by Schiff himself on the registry
of graduate exams. The candidate was less than brilliant and got the
minimum mark for passing exams and obtaining the degree (“laurea”):
66/110. In fact, the jury was typically constituted by 11 professors,
and each member was supposed to assign a mark from 1 (very low quality)
to 10 (very high quality). Schiff added this caustic note: “approved
with 66/110, which [the candidate] did not deserve even remotely.
I gave 1. [The candidate] has absolutely no idea of a chemical formula”.
The note was signed with the initials U. S., for UgoSchiff: the German
first name Hugo had been italianized to Ugo. In another graduation
session (Figure b), he commented, “90/110, [the candidate] did not deserve
the degree!!!”.
Figure 33
(a) Pungent handwritten note added by Schiff
in the registry of
graduate exams at the Royal Institute in Florence, graduation session
of June 9, 1905 (TS SCHIFF 026). (b) Note of January 22, 1914 (TS
SCHIFF 043). (c) Caricature of Ugo Schiff with Latin sentences that
he used to tell students during classes and in the lab [courtesy of
the Università di Firenze, Biblioteca di Scienze, sede Polo
scientifico, and Dipartimento di Chimica Ugo Schiff].
(a) pan class="Chemical">Pn>ungpan class="Chemical">ent handwrittpan class="Chemical">en note added by Schiff
in the registry of
graduate exams at the Royal Institute in Florence, graduation session
of June 9, 1905 (TS SCHIFF 026). (b) Note of January 22, 1914 (TS
SCHIFF 043). (c) Caricature of UgoSchiff with Latin sentences that
he used to tell students during classes and in the lab [courtesy of
the Università di Firenze, Biblioteca di Scienze, sede Polo
scientifico, and Dipartimento di Chimica UgoSchiff].
However, studpan class="Chemical">ents not only highly esteemed but loved their
grouchy
professor. This is confirmed by a cordial caricature of the old professor
drawn by a student (Figure c). Below the sketch, there are some Latin quotations that
Schiff used to tell students during classes or in the laboratory.
Some examples: “Rara avis in terris, [nigroque simillima cygno]”
(A rare bird upon the earth, [and exceedingly like a black swan],
Juvenal, Satires, VI, 165) was probably said to praise
the only student in the classroom able to answer a question by the
professor; “Dis aliter visum” (it seemed otherwise to
the gods: i.e., fate had different plans, Virgil, Aeneid, II, 428) was to comfort a student for the failure of an experiment;
“Sic itur ad astra” (thus one goes to the stars, Virgil, Aeneid, IX, 641) was to applaud a student for a successful
achievement in the lab.
Epilogue
The name
pan class="Chemical">Schiff will last in the language of chemistry as long
as this discipline will be studied and practiced. “n>an class="Chemical">Schiff base”
is one of the most frequently used expression in chemistry with an
associated surname, rivaled only by “Grignard reagent”.
What remains of Professor Schiff are the articles, the books, the
classes that formed thousands of chemists, from his students to the
students of his students, down to today students. However, UgoSchiff
gave important lessons also in the social side. The very last one
was the order of his funeral service, drawn by himself and published
in the local newspaper (La Nazione), on September
9, 1915, the day after his death: “ I order that my remains
will be carried out to Trespiano [the biggest cemetery of Florence]
for cremation, early in the morning, with no entourage, no speeches,
no flowers, in a coffin of raw timber, with a third class hearse,
more pauperum”. A final Latin quotation was more pauperum,
as poor people do.
Authors: Stuart J Rowan; Stuart J Cantrill; Graham R L Cousins; Jeremy K M Sanders; J Fraser Stoddart Journal: Angew Chem Int Ed Engl Date: 2002-03-15 Impact factor: 15.336
Authors: Prasenjit Mal; David Schultz; Kodiah Beyeh; Kari Rissanen; Jonathan R Nitschke Journal: Angew Chem Int Ed Engl Date: 2008 Impact factor: 15.336
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15
Figure 16
Figure 17
Figure 18
Figure 19
Figure 20
Figure 21
Figure 23
Figure 22
Figure 24
Figure 25
Figure 26
Figure 27
Figure 28
Figure 29
Figure 30
Figure 31
Figure 32
Figure 33