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. 2025 Jul 25;30(15):3115.
doi: 10.3390/molecules30153115.

Kinetics of Proton Transfer and String of Conformational Transformation for 4-Pyridone-3-carboxylic Acid Under External Electric Field

Ya-Wen Li  1 , Rui-Zhi Feng  2 , Xiao-Jiang Li  3 , Ai-Chuan Liu  3 , En-Lin Wang  4
Affiliations

Kinetics of Proton Transfer and String of Conformational Transformation for 4-Pyridone-3-carboxylic Acid Under External Electric Field

Ya-Wen Li et al. Molecules. .

Abstract

In order to explore the essence of the anticoccidiosis of anticoccidial drugs under bioelectric currents, the intermolecular double-proton transfer and conformational transformation of 4-pyridone-3-carboxylic acid were investigated by quantum chemistry calculations (at the M06-2X/6-311++G**, M06-2X/aug-cc-pVTZ and CCSD(T)/aug-cc-pVTZ levels) and finite temperature string (FTS) under external electric fields. The solvent effect of H2O on the double-proton transfer was evaluated by the integral equation formalism polarized continuum model. The results indicate that the influences of the external electric fields along the direction of the dipole moment on double-proton transfer are significant. The corresponding products are controlled by the direction of the external electric field. Due to the first-order Stark effect, some good linear relationships form between the changes of the structures, atoms in molecules (AIMs) results, surface electrostatic potentials, barriers of the transition state, and the external electric field strengths. From the gas to solvent phase, the barrier heights increased. The spatial order parameters (ϕ, ψ) of the conformational transformation could be quickly converged through the umbrella sampling and parameter averaging, and thus the free-energy landscape for the conformational transformation was obtained. Under the external electric field, there is competition between the double-proton transfer and conformational transformation. The external electric field greatly affects the cooperativity transfer, while it has little effect on the conformational transformation. This study is helpful in the selection and updating of anticoccidial drugs.

Keywords: 4-pyridone-3-carboxylic acid; FTS; conformational transformation; double-proton cooperativity transfer; kinetics.

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Conflict of interest statement

Authors Xiao-Jiang Li, Ai-Chuan Liu were employed by the company Shanxi North Xingan Chemical Industry Limited Company, Taiyuan, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Scheme 1
Scheme 1
Structure of typical anticoccidial drugs.
Figure 1
Figure 1
Hydrolysis of nequinate (a), proton transfer (PT) (b(1)) (intermolecular PT indicated by two arrows with “PT”) and conformation transformation (b(2)) of 4-pyridone-3-carboxylic acid under external electric field (coordinate axes parallel to which the external electric fields (Ex, Ey, Ez) are applied), and the blue arrow labeled “μ” indicates the direction of the dipole moment.
Figure 2
Figure 2
Convergence of the collective variables during string evolution under the different external electric fields.
Figure 3
Figure 3
PMF of the conformational transformation of 4-pyridone-3-carboxylic acid under the different external electric fields.
Figure 4
Figure 4
3D surface plot of the free energy landscape with transition states from conformation 1 to 2 under the different external electric fields.
See this image and copyright information in PMC

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