Ab Initio Molecular Dynamics Simulations of Aqueous Glucosamine Solutions: Solvation Structure and Mechanism of Proton Transfer from Water to Amino Group

Abstract

Glucosamine is a component of many cellular glycoproteins that constitutes the cartilage, and it has several biological activities, such as anti-inflammatory, antioxidant, antifibrotic, and anticancer, and has been used in arthritis and dermatological treatments. Considering that the biological activities of glucosamine occur mainly in an aqueous environment, it is essential to understand the effects of an aqueous solvent on its geometric and electronic parameters using ab initio molecular dynamics. The Car–Parrinello molecular dynamics results show that the hydroxyl groups form stable hydrogen bonds with the water molecules with intensities ranging from weak (closed-shell interaction) to intermediate (partially covalent interactions). The H bonds formed between the amino group and the water molecule range from weak (closed-shell) to strong (covalent), and it shows an infinity residence time. The natural bonding orbital (NBO) approach was applied to analyze the effects of charge-transfer interactions on the behavior of the hydrogen bonds. The main contribution to stabilizing energies comes from n → σ* hyperconjugation and explains the stability of the H bonds. The energy barrier for the proton transfer from water to the amino group is 0.88 kcal/mol, and the van der Waals complex energy is 0.3 kcal/mol. The low protonation energy barrier shows that glucosamine can be protonated in an aqueous environment at room temperature, which helps to explain many of its biological activities.

Proton transfer at subkelvin temperatures

“…Finally, the low temperature of the helium matrix would have a marked effect on reactions that are exothermic but inhibited by small energy barriers, such as proton transfer from water to an amino group. 63 Fig. 1.…”

Hydration behaviors of nonfouling zwitterionic materials

“…To analyze HB strength and net charge of zwitterion, the quantum theory of atoms in molecules (QTAIM) 40,41 framework was employed for the zwitterion-HB-water complexes and zwitterions with total 119 solvation water molecules, respectively, using the same congurations in the SAPT analysis. For small zwitterion-HB-water complexes, we computed their charge densities using Gaussian16 soware 42 with the hybrid functional M062X and the 6-311++G(d,p) basis, 43 and analyzed the HB strength in Fig. 4d (right) from the ratio between kinetic and potential energy densities (−G(r)/V(r)) at the bond critical point between zwitterionic oxygen and water hydrogen using the Multiwfn soware.…”

Virtual Issue on Proton Transfer

“…Four of the publications explore proton transfer in ionic liquids with spectroscopic methods and molecular dynamics simulations. − Some of these studies elucidate the proton conduction mechanisms in protic ionic liquids, exhibiting some similarities to the Grotthuss mechanism in aqueous acidic solution. Other papers , use molecular dynamics simulations to study specific proton transfer reactions occurring in aqueous solution, gas phase, and solid state.…”