Quantum chemical simulation of the silica-anaesthetic, silica-polymer, and polymer-anaesthetic interactions.

Using semiempirical PM3 method, a comparative quantum chemical estimation has been carried out of the energy of articaine adsorption on the surfaces of the following composite materials: silica-anaesthetic, polymer-anaesthetic, and silica-polymer-anaesthetic. It has been found that adsorption on silica surface takes place due to electrostatic and nonspecific interactions. The data of quantum chemical calculations of the structures of composite materials may be useful in the creation of different forms of medicine preparations with adjustment characteristics.

Background

Silica-polymer systems, due to their organic-inorganic nature, are perspective for use as immobilized forms of medicine preparations [1-4]. In particular, the inclusion of anaesthetics into such nanocomposites may provide the prolongation of their activity, rise bioaccesibility, and reduce irritating influence on the organism [5].

Model conceptions on silica-anaesthetic, silica-polymer, and polymer-anaesthetic interactions are of great importance when creating application forms of anaesthetics. The developed method of approach will permit the prognosticating of adjusting educe of preparations as dependent on the chemical nature of components of the composite material. Articaine is widely used in anaesthesia practice. Its inclusion into the composition of application preparations will permit a decrease in their toxic influence on the patients with high sensitiveness.

In the present work, a comparative quantum chemical analysis has been performed of the values of adsorption energies in the silica-anaesthetic, polymer-anaesthetic, silica-polymer, and silica-polymer-anaesthetic systems using semi-empirical PM3 method [6,7].

Methods

The initial coordinates of atoms in the structures under investigation were determined by molecular mechanics method using HyperChem7 program taking into account electrostatic and disperse forces between the cluster host (silica, polymer) and the guest molecule (articaine). Coordinates found by this way were used in further calculation of the electronic structure of nanocomposites by semi-empirical PM3 method by means of MOPAC 2012 14.083 W program which gives an adequate description of both intermolecular interactions and energetics of cluster formation.

Models for silica structure are presented as two planes of nanocluster (SiO2)m with different surface nature. In the first case, there are both sides of hydroxylated surfaces of the plane (O105Si50H50); in the second one, the hydroxyls of one side of the plane are changed by methyl groups (nanocluster C7O99Si50H64). A model of polymer was simulated by a nanocluster consisting of seven glucose molecules connected to each other with 1.6- of α-1.6 glycosidic linkages between glucose molecules, while branches begin from α-1.3 linkages. Anaesthetic articaine has the formula C13N2O3SH20. In silica nanoclusters, the uncompensated valences of edged Si atoms were compensated by two hydrogen atoms (for conservation of sp3 hybridization) [8]. Model structures under investigation for articaine (1); polymer (2); silica nanoclusters (3-5); binary composites: polymer-articaine (2-1), silica-articaine (3-1, 4-1, 5-1), and silica-polymer (3-2, 4-2); and ternary composites: silica-polymer-articaine (3-2-1, 4-2-1) are represented in Figure 1.

Figure 1

Model structures under investigation. Structures of articaine (1); polymer (2); silica nanoclusters (3, 4, 5); binary composites: polymer-articaine (2-1), silica-articaine (3-1, 4-1, 5-1), and silica-polymer (3-2, 4-2); and ternary composites: silica-polymer-articaine (3-2-1, 4-2-1).

Results and discussion

In the present work, the total bonding energy Ebd, the values of adsorption energy Ead of articaine on silica and polymer surfaces, and also the charge magnitude on the articaine molecule in binary (polymer-articaine, silica-articaine, silica-polymer) and ternary (silica-polymer-articaine) composite materials have been calculated. Taking into account the use of supramolecular approximation for modelling of adsorption interactions, the values of adsorption energy of articaine on the surfaces under investigation have been determined from the formula [9]:

As it can be seen from Table 1, the values of adsorption energy of articaine molecule Ead as dependent on the change in the surface nature become variable in the interval from −22 to −55 kJ/mol that by the order of magnitude of adsorption energy is comparable with the energy of alone hydrogen bond of O-H…O or O-H…N type. The increase of adsorption energy of articaine molecule Ead on the silica-dextrane composites (3-2 and 4-2) can be probably ascribed to 2.3 times rise of surface contact for dextrane (727 Ǻ2) relatively to articaine (315 Ǻ2). It should be noted that the value of adsorption energy of articaine Ead on hydroxylated (hydrophilic) surfaces of the silica matrix (4-1, 5a-1, 4-2-1) is always from 2.0 to 4.0 kJ/mol greater than that on the methylated (hydrophobic) surfaces.

Table 1

Model nanoclusters and composite values of of articaine, ∆ , and and

Nanoclusters a and composite materials	E bd (eV)	∆ Е ad (kJ/mol)	∆ ρ ( e )	Е HOMO (eV)	Е LUMO (eV)
1	−3,240.84716			−9.265	−1.015
2	−15,685.88357			−10.408	−1.551
3	−44,167.94579			−4.912	4.136
4	−51,616.84388			−5.324	4.351
5	−47,964.94665			−5.557	4.143
2-1	−18,926.95902	−22,029	0.0038
3-1	−47,409.11363	−30,945	−0.0352
4-1	−54,858.02645	−323,665	−0.1092
5а-1	−51,206.36105	−54,737	−0.0510
5b-1	−51,206.33845	−52,557	−0.0323
3-2	−59,855.50188	−161,393	−0.1190	−5.122	2.865
4-2	−67,304.03594	−126,265	−0.1366	−5.709	0.133
3-2-1	−63,096.64194	−28,264	−0.0088

aThe structures of nanoclusters of composites are given in accordance with Figure 1.

Besides, the extent of charge transfer ∆ρ between interacting components for all the composites studied has limits from +0.0038 е tо –0.0510 е. We suppose that the obtained small values of both adsorption energies Ead and extent of charge transfer for silica of different nature and dextrane may be connected with realizing of adsorption processes in such systems mainly due to electrostatic and nonspecific interactions.

As it has been mentioned above, the adsorption of articaine molecule on modified silica surfaces gives changes not only of the extent of charge transfer but also the sign. Really when articaine molecule is adsorbed on dextrane, it becomes positively charged whereas other cases give Δρ < 0. An analysis of energy values of the frontier molecular orbitals (EHOMO, the highest occupied molecular orbital, and ELUMO, the lowest vacant molecular orbital, characterizing respectively electron-donating and electron-accepting properties of the systems) demonstrates that the change of the sign for ∆ρ at articaine molecule is defined by the sign of difference ΔЕ = ЕHOMO(articaine) − ЕLUMO(sorbent) [10].

The observed change of the charge value ∆ρ for studied composites gives evidence about the change of electron state of adsorbed molecule. Analysing change of differential electronic density on atoms of the adsorbed molecule in relation to that of not sorbed one δρi = Δρiad − Δρi, it is possible to define the positions of the atoms the most perturbed due to adsorption. Dependencies of δρi for composites dextran-articaine (2-1), methylated silica-articaine (3-1), hydroxylated silica-articaine (4-1), and methylated silica-dextran-articaine (3-2-1) are given as an example in Figure 2.

Figure 2

Dependencies of . For composites dextran-articaine (2-1), methylated silica-articaine (3-1), hydroxylated silica-articaine (4-1), and methylated silica-dextran-articaine (3-2-1).

The absolute changes in δρi on atoms of articaine (Figure 2) in both adsorbed and non-adsorbed states depend on the nature of sorbent surface, but short contacts with the surfaces of all the composites studied are formed mainly by such articaine atoms: carbonyl-type oxygen atom О2; methyl groups С4Н3, С21Н3, and С34Н3; propyl group С8-С10; and atoms of thiophene ring.

Conclusions

It has been found that adsorption in silica surface takes place due to electrostatic interactions. For articaine adsorption on hydroxylated silica surface, the energy value is 1.5 to 4.0 kJ/mol higher than that on methylated silica. An analysis of the values of adsorption energy for articaine in binary (‘dextran-articaine’ and ‘silica-articaine’) and ternary (‘silica-dextran-articaine’) composites shows that changing the nature of the sorbent surface it is probable to affect on the adsorption energy. The results of quantum chemical calculations of the structures of composite materials may be useful in the creation of different forms of medicine preparations with adjustment characteristics.