Guest-adaptable and water-stable peptide-based porous materials by imidazolate side chain control.

The peptide-based porous 3D framework, ZnCar, has been synthesized from Zn(2+) and the natural dipeptide carnosine (β-alanyl-L-histidine). Unlike previous extended peptide networks, the imidazole side chain of the histidine residue is deprotonated to afford Zn-imidazolate chains, with bonding similar to the zeolitic imidazolate framework (ZIF) family of porous materials. ZnCar exhibits permanent microporosity with a surface area of 448 m(2)  g(-1) , and its pores are 1D channels with 5 Å openings and a characteristic chiral shape. This compound is chemically stable in organic solvents and water. Single-crystal X-ray diffraction (XRD) showed that the ZnCar framework adapts to MeOH and H2 O guests because of the torsional flexibility of the main His-β-Ala chain, while retaining the rigidity conferred by the Zn-imidazolate chains. The conformation adopted by carnosine is driven by the H bonds formed both to other dipeptides and to the guests, permitting the observed structural transformations.

Metal–organic frameworks (MOFs) are crystalline porous materials composed of inorganic nodes, either single ions or clusters of ions, bridged by organic linkers through metal–ligand coordination bonds.[1] Recently, several biomolecules, such as amino acids,[2] nucleobases,[3] saccharides,[4] and peptides,[5] were used as organic linkers in MOF synthesis, mainly because of the diversity of their metal binding sites. The incorporation of biomolecules in MOFs also attracts particular attention because they can improve the biocompatibility of the final products, enhance the structural and chemical diversity of the internal surfaces of MOFs, and afford chiral frameworks that may have unique separation and catalytic properties.[6]

Peptides are particularly interesting as linkers because dipeptides with hydrophobic residues that are held together by H bonds form metal-free purely peptide-based porous materials. These structures are divided into two groups, the Val-Ala compounds with hydrophobic pores and the Phe-Phe compounds with hydrophilic pores.[7] The Val-Ala structures exhibit typical CO2 and CH4 adsorption for microporous materials.[8]

In MOFs, peptides have the ability to act as connecting ligands as they have at least one amino and one carboxylic acid terminus that can coordinate metal ions. The dipeptides Gly-Ala and Gly-Thr thus connect Zn2+ ions to form two topologically distinct 2D-layered framework compounds, Zn(Gly-Ala)2 and Zn(Gly-Thr)2, respectively.[9] The former is a flexible porous material that displays an adaptable pore conformation, which evolves continuously from an open to a partially disordered closed structure in response to the level of guest loading. The latter is structurally rigid to guest loss in a manner characteristic of rigid MOFs and exhibits permanent porosity with a surface area of 200 m2 g−1 after solvent removal, as the framework is stabilized by the additional H bonding between the OH functional group from the threonine side chain and the NH2 terminal group. These two examples clearly show how diverse the structures can be and the strong control of adsorption behavior arising from small changes in the peptide unit.

Here we present a new peptide-based MOF, ZnCar⋅DMF, which is assembled from Zn2+ and carnosine (Car), a natural dipeptide with the molecular structure β-alanyl-l-histidine. The peptidic chain of carnosine contains an extra CH2 group compared to classic dipeptides, because of the β-amino acid structure of β-alanine. The histidine residue incorporates the imidazole moiety that serves as an additional metal binding site, and thus carnosine has two more potential linking points compared to Gly-Ala and Gly-Thr. In reported histidine-containing framework compounds the imidazole ring is neutral and binds only one metal atom at N3.[10] ZnCar⋅DMF is a 3D framework compound in which each carnosine molecule links four tetrahedral Zn cations, two of which are bridged by the deprotonated imidazolate ring. The structure is flexible and displays 1D permanent porosity upon removal of DMF. It is a microporous material with a specific surface area of 448 m2 g−1 and exhibits strong binding affinity for small molecules, such as CO2 and CH4. This MOF is not dissolved or decomposed in either H2O or MeOH. Moreover, after resolvation in MeOH and H2O, it adopts structures different from that of the as-made or desolvated material. Single-crystal X-ray diffraction studies showed that this flexibility is driven by H bonds formed between the guests and the dipeptide, leading to different torsional conformations of carnosine.

Crystals of ZnCar⋅DMF in the shape of rectangular prisms and 50 to 100 μm in length (Supporting Information, Figure S1) were obtained from the reaction of zinc nitrate with carnosine in DMF/H2O at 100 °C for 12 hours (see the Experimental Section in the Supporting Information). Under these conditions, both the imidazole N1 and the carboxy group of the carnosine are deprotonated to form the Car2− anion, allowing the formation of a 4:4 motif with Zn2+ (Scheme 1). The Zn cations are tetrahedrally coordinated to four carnosine ligands (Scheme 1), and each ligand is coordinated to four Zn2+ ions by the C-terminal His carboxylate group, the N-terminal Ala amine group, and the two nitrogen atoms of the imidazole ring (Scheme 1). The chemistry and the bridging connectivity between the side chain imidazole of histidine and the Zn cations are reminiscent of those seen in ZIF compounds.[11] The molecular cyclic tetramer [Au(gly-L-his3−)]4⋅10 H2O is the only other known compound of histidine where metal–imidazolate bonding is employed.[12]

Scheme 1

Formation of ZnCar⋅DMF from the reaction between Zn(NO3)2 and carnosine.

ZnCar⋅DMF crystallizes in the chiral monoclinic space group P21 and its 3D structure is directed by the carnosine conformation (Figure 1 a), as the Zn cations connected to the histidine moiety define a plane and the residue of the N-terminal β-alanine is extended to the third dimension. The imidazolate rings (im) and Zn cations form a zigzag chain where the rings adopt a trans conformation (Figure 1 b) and the Zn-im-Zn angle is 138°(Figure S2), which is smaller than the 145° angle found in ZIFs.[11a] This chain is similar to the linear structures of univalent metal–imidazolate compounds.[13] The chains are linked through the histidine carboxylate group (Figure 1 b) to form undulating layers (parallel to the 100 plane) that are interconnected by the antiparallel-oriented β-alanine residues (Figure 1 c). The framework is further stabilized by two H bonds, an intramolecular bond between the carboxy oxygen atom and amino hydrogen atom of β-alanine, and an intermolecular bond between the carboxylate oxygen atom of histidine and the neighboring amide hydrogen atom (Figure 1 a and c). The arrangement of carnosine forms 1D square-shaped pores, filled with DMF and running parallel to the crystallographic b axis (Figure 1 d). The chiral shape of the pore walls is depicted using the Connolly surface representation (Figure 1 e). The pores can be viewed as relatively large cavities, with diameters of d1=5.18 Å, connected in a zig-zag fashion by narrow channels with diameters of d2=3.78 Å.

Figure 1

a) 3D conformation of carnosine connected to four Zn cations. The dashed line corresponds to the intramolecular H bond between a carboxy oxygen atom and an amino hydrogen atom. Three Zn cations are bound to histidine (above the line) and the fourth to β-alanine (below the line). b) Zn cations and imidazolate rings form the zig-zag chain (highlighted) that is the rigid part of the structure. The chains are linked through the histidine carboxylate group. c) Undulating layers of imidazolate rings interconnected by antiparallel-oriented β-alanine residues. Intermolecular H bonds are formed between the carboxylate oxygen atom and the amide hydrogen atom. d) Space-filling representation of ZnCar viewed along the b axis, showing the 1D pores. e) Connolly surface representation of the pore walls, calculated with a probe radius of 1.4 Å. The pores consist of cavities with diameters of d1=5.18 Å and narrow channels with diameters of d2=3.78 Å.

The structure and the composition of ZnCar⋅DMF, obtained from single-crystal X-ray diffraction data are in good agreement with the characterization results of the bulk sample. The powder XRD pattern perfectly matches the simulated pattern from the single-crystal structure and is indexed to the same unit cell (Figure S3 and Table S1). CHN analysis results are very close to theoretical values (Table S2) and the DMF content, calculated as 20 wt % from the single-crystal data, was verified by thermogravimetric analysis (TGA; Figure S4). The solid-state 13C CPMAS NMR spectrum of ZnCar⋅DMF displays all the expected resonances for carnosine and three resonances for DMF (Figure S5) at room temperature.

The ZnCar⋅DMF framework is structurally flexible and displays permanent porosity after the removal of DMF, as demonstrated by the variable-temperature single-crystal X-ray diffraction data. While the crystallinity of the material is retained over the whole temperature range that was studied, the unit-cell volume decreases sharply from 762.82 to 726.78 Å3 (by ≈5 %) between 388 and 394 K as DMF is removed from the pores (Figure S6). The relaxation of the ZnCar framework from the DMF-solvated state at 388 K (Figure 2 a) to the desolvated state at 394 K (Figure 2 b) results in an alternate linker conformation. The torsion angles of the peptidic chain change by 20–30° (Figure S7) with the exception of the rigid ω angle C7-N8-C9-C14, which corresponds to the peptide bond itself. The structure of the pore was also altered, having cavities with diameters of d1=4.58 Å connected by channels with diameters of d2=4.18 Å (Table S3). In contrast, the three torsional angles responsible for the orientation of the imidazolate ring and the carboxylate group on histidine each changed by less than 2°, indicating the rigidity of the bc planes shown in Figure 1 b.

Figure 2

The structures of a) ZnCar⋅DMF, b) desolvated ZnCar, c) resolvated ZnCar⋅MeOH, and d) resolvated ZnCar⋅H2O. ZnCar⋅DMF, ZnCar, and ZnCar⋅MeOH show one type of pore with square or parallelogram shape. ZnCar⋅H2O has two types of pores.

The bulk desolvation of ZnCar⋅DMF was achieved by evacuation on a high-vacuum line (10−5 mbar) at 130 °C for 5 hours. The structure of the evacuated sample, ZnCar, was confirmed by powder XRD and the complete removal of DMF was verified by TGA (Figure S8). The porous properties of desolvated ZnCar were investigated with the CO2 adsorption–desorption isotherm (Figure S9) obtained at 195 K up to 1 bar. ZnCar is purely microporous, as the isotherm shape corresponds to that of type I according to the IUPAC classification. The BET surface area is calculated as 448 m2 g−1 using the relative pressure range, 0.01