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][2][3][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.

Results and discussion
In the present work, the total bonding energy E bd , the values of adsorption energy E ad 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-polymerarticaine) 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 E ad 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 E ad 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 Ǻ 2 ) relatively to articaine (315 Ǻ 2 ). It should be noted that the value of adsorption energy of articaine E ad 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.
Besides, the extent of charge transfer Δρ 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 E ad 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 (E HOMO , the highest occupied molecular orbital, and E LUMO , the lowest vacant molecular orbital, characterizing respectively electrondonating and electron-accepting properties of the systems) demonstrates that the change of the sign for Δρ at articaine molecule is defined by the sign of difference ΔЕ = Е HOMO (articaine) − Е LUMO (sorbent) [10].
The observed change of the charge value Δρ 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 δρ i = Δρ i ad − Δρ i , it is possible to define the positions of the atoms the most perturbed due to adsorption. Dependencies of δρ i for composites dextran-articaine (2-1), methylated silica-articaine (3-1), hydroxylated silicaarticaine (4-1), and methylated silica-dextran-articaine (3-2-1) are given as an example in Figure 2.
The absolute changes in δρ i 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: carbonyltype oxygen atom О 2 ; methyl groups С 4 Н 3 , С 21 Н 3 , and С 34 Н 3 ; 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 'silicaarticaine') 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.