Effect of Non-Enzymatic Collagen Glycation on Intermolecular Interaction with Optical Clearing Agents: A DFT Study of the Thermodynamics and Structure of Complexes with DMSO, Urea, and Glycerol
K. V. Berezin1,2, E. Yu. Stepanovich2, A. M. Likhter2, E. V. Grabarchuk2, K. N. Dvoretsky3, Yu. Yanina1, V. V. Tuchin1,4,5
1 N.G. Chernyshevsky Saratov State National Research University, Saratov, Russia
2 V.N. Tatishchev Astrakhan State University, Astrakhan, Russia
3 V.I. Razumovsky Saratov State Medical University, Saratov, Russia
4 National Research Tomsk State University, Tomsk, Russia,
5 Institute of Precision Mechanics and Control, Federal Research Center "Saratov Scientific Center of the Russian Academy of Sciences," Saratov, Russia.
Abstract
The structure and thermodynamic parameters of intermolecular complexes between optical clearing agents (DMSO, urea, glycerol) and model collagen fragments
representing successive stages of non-enzymatic glycation (lysine → fructosyllysine → glucosepane) have been modeled using density functional theory (DFT) with
B3LYP and wB97XD functionals in 6-31+G(d) and 6-311+G(3d,p) basis sets. It is shown that at the early stage of glycation (formation of the Amadori product — fructosyllysine),
neutralization of the positively charged ε-NH₃⁺ group of lysine leads to a significant decrease in the enthalpy of association with clearing agents
(for DMSO from –88.3 to –64.7 kJ/mol; for urea from –84.2 to –57.7 kJ/mol) and a drop in the equilibrium constant by 5 orders of magnitude. At the late stage
(formation of glucosepane), the association enthalpy further decreases by almost half compared to the Amadori product. Structural analysis of hydrogen bonds reveals
that the decrease in enthalpy is due to the loss of strong ion-dipole interactions between charged amino groups and the agent molecules, replaced by weaker classical
and non-classical hydrogen bonds with the hydroxyl groups of sugar moieties. The obtained results explain the experimentally observed decrease in the optical clearing
efficiency of glycated tissues and are consistent with optical coherence tomography data.
Speaker
Kirill V. Berezin
N.G. Chernyshevsky Saratov State National Research University, Saratov
V.N. Tatishchev Astrakhan State University, Astrakhan
Russia
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