First-Principles Study of the Dispersion Effects in the Structures and Keto-Enol Tautomerization of Curcumin.

Noncovalent interactions, such as dispersion, play a significant role in the stability of flexible molecules, such as curcumin. This study revealed the importance of dispersion correction in the structure and keto-enol tautomerization of curcumin, which has rarely been addressed in computational studies. We rigorously constructed all possible unique curcumin conformers in the enol and keto forms within the first-principles framework. Regardless of the different environments, we carefully explained the agreement between the computational geometry (in the gas phase) and the experimental measurement (in the polymorph) by using dispersion correction. The calculation results for the aqueous solution of conformational abundance, thermochemistry, and reaction kinetics support the experimental observations after considering the dispersion correction. The study also suggests a water-catalyzed mechanism for keto-enol tautomerization, where dispersion correction plays a role in decreasing the energy barrier and making the keto form thermochemically and kinetically favorable. Our results could be helpful in future computational studies to find a method for increasing the aqueous solubility of curcumin; hence, the potential of curcumin as a multifunctional medicine can be fully achieved.

A Density-Functional Study of the Conformational Preference of Acetylcholine in the Neutral Hydrolysis.

Acetylcholine, which is associated with Alzheimer's disease, is widely known to have conformers. The preference of each conformer to undergo neutral hydrolysis is yet to be considered. In this study, we employed density-functional calculations to build the conformers and investigated their preference in one-step neutral hydrolysis. The results showed the preference in ten possible hydrolysis pathways involving seven acetylcholine conformers (reactant), four transition state structures, and two choline conformers (product). Three out of the seven acetylcholine conformers predicted from the results confirmed experimental findings on the conformers stability. We suggested that two out of ten possible pathways were observed in the experimental results based on agreement in reaction energy. Eventually, this study will emphasize the importance of considering acetylcholine conformers in its hydrolysis study.

The transition state conformational effect on the activation energy of ethyl acetate neutral hydrolysis.

We report a first-principles study on ethyl acetate neutral hydrolysis in which we focus on the activation energy variation resulting from the conformational effect in the transition state. We use the conformers of ethyl formate, ethyl acetate, ethyl fluoroacetate, and ethyl chloroacetate as the ester models and one water molecule with a one-step reaction mechanism. We also consider the long-range interaction and the surrounding water in the form of PCM. Our results show that the various conformers yield a significant range of activation energy. Moreover, the gauche conformer has lower activation energy than the trans conformer. The activation energy in its own right is lowered by the halogen atoms. Finally, we remark that the long-range correction and PCM stabilize the transition state geometry but raise the activation energy.