Unraveling the N-Co coordination mechanism in chitosan-cobalt complexes: Structural elucidation and in vivo cobalt supplementation effect

Published: 8 December 2025| Version 1 | DOI: 10.17632/6hsxwtdpks.1
Contributors:
shuai Wang, Shiping Wang, Zhihao Zheng, Zhangkong Wei, Lixia Shi, Xiaoyan Jia, Li Li, Jing Ren, lei yang, Yannan Ma, Ji Zhang, jianping wu, Junlong Wang

Description

The computational chemistry section employed quantum chemical tools (density functional theory DFT) to investigate the coordination mechanism between chitosan (CS) and Co(II). The core research hypothesis is that Co(II) tends to accept electrons from the -NH₂ groups of CS rather than the -OH groups to form CS-Co(II) complexes. The data analysis focused on four key aspects: confirmation of coordination sites, screening of coordination modes, electron transfer mechanism, and intrinsic nature of chemical bonding. Chitobiose was used as a simplified model of CS. Three chitobiose configurations were optimized via DFT calculations at the B3LYP/6-311G(d,p) basis set level (with the LanL2DZ basis set for Co(II)), followed by comparisons of their energies, frontier molecular orbital (FMO) parameters. The coordination sites were confirmed by combining electrostatic potential (ESP) and average local ionization energy (ALIE) analyses. The interaction energy, enthalpy change, and Gibbs free energy of four coordination models (pendant, bridge 1, bridge 2, and central) were calculated to screen the most thermodynamically favorable mode. The direction of electron transfer was elucidated using FMO analysis (by examining the electron cloud distribution of HOMO/LUMO) and charge decomposition analysis (CDA). The intrinsic nature of the chemical bond was revealed through ESP (to localize regions of positive electrostatic potential), interaction region indicator (IRI, to distinguish coordination bonds from van der Waals interactions), electron localization function (ELF, to evaluate electron delocalization), and atoms in molecules (AIM, to calculate topological parameters of bond critical points). Notably, ALIE and ESP analyses confirmed that the -NH₂ groups of CS are the preferred coordination sites for Co(II). The central model exhibited the lowest energy. FMO and CDA results demonstrated that CS acts as an electron donor while Co(II) serves as an electron acceptor, with electrons transferring from the -NH₂ groups of CS to Co(II). The N-Co(II) bond is predominantly ionic with a weak covalent character.

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The quantum chemical modeling of the target molecular fragments (constructed in the Materials Studio program) within the framework of DFT was performed using the Gaussian 16 and GaussView 06 software suite with the hybrid density functional B3LYP/6-311G(d, p) and LanL2DZ. The 6-311G(d, p) basis set was adopted for C, N, O, H, the LanL2DZ basis set had been used in order to represent the Co(Ⅱ) ion. In choosing the spin state of Co(Ⅱ), quartet state configurations were considered since they were found to be energetically more stable than the corresponding doublet state counterparts. An abridged DFT computation was employed to scrutinize the interaction of Co (II) ions with CS. The vibrational frequency and electronic energy computations were conducted on the optimized molecular structures to obtain zero-point vibrational energy and associated thermochemical properties. For Gaussian results, the electrostatic surface potential (ESP), average local ionization energy (ALIE), atom in molecules (AIM), frontier molecular orbitals (FMO), charge decomposition analysis (CDA), interaction region indicator (IRI) and electron localization function (ELF) analyses were performed using Multiwfn 3.8 programs. All the ESP, ALIE, AIM, IRI, FMO and ELF pictures were rendered by Visual Molecular Dynamics (VMD) 1.9.4 program.

Institutions

Categories

Quantum Chemical Calculations

Funders

  • Gansu Education Department
    Ministry of Education of the People's Republic of China
    Gansu, China
    Grant ID: 2020C-21
  • Central Leading Local Science and Technology Development Project
    Grant ID: 24ZYQA039, 24ZYQA040
  • Gansu Province Scientific Research Fund
    Grant ID: 23JRRA1482, 23JRRA1295
  • Excellent Doctoral Candidates Project of Gansu Province
    Grant ID: 24JRRA151
  • Lanzhou Scientific and Planned Projects
    Grant ID: 2023-3-4, 2023-2- 21, 2023-ZD-27
  • Key Laboratory of National Health Commission Fund
    Grant ID: 23GSSYA-13

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