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

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.

本计算化学研究采用量子化学工具（密度泛函理论（DFT）），探究壳聚糖（CS）与二价钴离子（Co(II)）之间的配位机制。核心研究假设为：Co(II)更倾向于从CS的氨基（-NH₂）而非羟基（-OH）获取电子，以形成CS-Co(II)配合物。数据分析围绕四大核心方向展开：配位位点确认、配位模式筛选、电子转移机制以及化学键的内在本质。研究采用壳二糖作为CS的简化模型，在B3LYP/6-311G(d,p)基组（其中Co(II)采用LanL2DZ基组）水平下，通过DFT计算优化了三种壳二糖构型，并对比了它们的能量与前线分子轨道（FMO）参数。通过结合静电势（ESP）与平均局域电离能（ALIE）分析，确认了配位位点。针对四种配位模型（悬挂式、桥联1型、桥联2型与中心型），计算了其相互作用能、焓变与吉布斯自由能，以筛选出热力学上最有利的配位模式。利用前线分子轨道（FMO）分析（通过考察最高占据分子轨道/最低未占据分子轨道（HOMO/LUMO）的电子云分布）与电荷分解分析（CDA），阐明了电子转移方向。通过静电势（ESP，用于定位正静电势区域）、相互作用区域指示器（IRI，用于区分配位键与范德华相互作用）、电子定域化函数（ELF，用于评估电子离域程度）以及分子中的原子（AIM，用于计算键临界点的拓扑参数），揭示了化学键的内在本质。值得注意的是，ALIE与ESP分析证实，CS的氨基（-NH₂）是Co(II)优先选择的配位位点。中心型构型展现出最低的能量。FMO与CDA结果表明，CS作为电子供体，Co(II)作为电子受体，电子由CS的氨基（-NH₂）转移至Co(II)。N-Co(II)键以离子性为主，同时带有微弱的共价特征。