Silva Camilla Fonseca, Nascimento Clebio Soares, Borges Keyller Bastos
Department of Chemistry, ICEX, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte, Minas Gerais 31270-901, Brazil.
Department of Natural Sciences, DCNAT, Federal University of São João del-Rei, Campus Dom Bosco, Praça Dom Helvécio 74, Fábricas, São João del-Rei, Minas Gerais 36301-160, Brazil.
ACS Omega. 2025 Jan 21;10(4):3890-3897. doi: 10.1021/acsomega.4c09559. eCollection 2025 Feb 4.
Chiral capillary electrophoresis (CCE) represents an effective technique for enantioselective separations. However, additional techniques may be necessary to determine the enantiomers migration order (EMO) and elucidate the chiral recognition mechanism. This study details the development and optimization of a CCE method for the enantioseparation of amlodipine (AML). Furthermore, it contributes computationally to determining the EMO and the mechanisms responsible for chiral discrimination. The study proposed the optimization of several key parameters in CCE, including the type, concentration and pH of the background electrolyte, as well as the concentration of the chiral selector. In line with previous research, only one anionic cyclodextrin, carboxymethyl-β-cyclodextrin (CM-β-CD), was evaluated as the chiral selector. Following optimization, the most favorable results were achieved using 50 mM phosphate background electrolyte pH 4.0 with 2.5 mg mL CM-β-CD. These conditions enabled baseline separation of AML enantiomers, reduced analysis time, and minimized consumption of the chiral selector. Calculations were conducted using a sequential methodology, beginning with the PM3 semiempirical followed by density functional theory (DFT) calculations. The theoretical analysis indicated that differences in Δ and Δ values are reliable indicators for predicting the EMO. Specifically, the (-)-()-AML/CM-β-CD complex exhibited superior energetic characteristics compared to the (+)-()-AML/CM-β-CD complex, likely due to differences in their intermolecular interactions, including hydrogen bonds and electrostatic interactions, consequently, this finding can be related to elongation migration time within the electrophoretic system. These results underscore the synergistic benefits of computational and experimental approaches in elucidating chiral discrimination mechanisms and identifying EMO in CCE.
手性毛细管电泳（CCE）是一种有效的对映体选择性分离技术。然而，可能需要额外的技术来确定对映体迁移顺序（EMO）并阐明手性识别机制。本研究详细介绍了一种用于氨氯地平（AML）对映体分离的CCE方法的开发和优化。此外，它在计算上有助于确定EMO和负责手性识别的机制。该研究提出了对CCE中几个关键参数的优化，包括背景电解质的类型、浓度和pH值，以及手性选择剂的浓度。与先前的研究一致，仅评估了一种阴离子环糊精，即羧甲基-β-环糊精（CM-β-CD）作为手性选择剂。经过优化，使用50 mM pH 4.0的磷酸盐背景电解质和2.5 mg/mL的CM-β-CD可获得最有利的结果。这些条件能够实现AML对映体的基线分离，减少分析时间，并使手性选择剂的消耗最小化。计算采用顺序方法进行，首先是PM3半经验计算，然后是密度泛函理论（DFT）计算。理论分析表明，Δ和Δ值的差异是预测EMO的可靠指标。具体而言，（-）-（）-AML/CM-β-CD复合物表现出比（+）-（）-AML/CM-β-CD复合物更优异的能量特征，这可能是由于它们分子间相互作用的差异，包括氢键和静电相互作用。因此，这一发现可能与电泳系统中的延长迁移时间有关。这些结果强调了计算和实验方法在阐明手性识别机制和确定CCE中的EMO方面的协同优势。
