Ferjani Hela
Center for Innovation and Entrepreneurship, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Kingdom of Saudi Arabia.
J Mol Graph Model. 2025 Jun;137:109012. doi: 10.1016/j.jmgm.2025.109012. Epub 2025 Mar 12.
5-Flucytosine (FC) exhibits an advanced solid-state structure, which presents challenges for its pharmaceutical development. This paper presents experimental, and theoretical studies of a novel pharmaceutical salt, fluorocytosinium chloride, HFC.Cl. Single crystal X-ray diffraction (SCXRD) investigation indicates that HFC.Cl forms crystals in the monoclinic system and P2/c space group. The structure is maintained by a series of hydrogen bonding interactions, comprising N-H···Cl, N-H···O, and C-H···F. In addition, noncovalent anion···π interactions between chloride anions and HFC cations play a role in establishing a three-dimensional network. Hirshfeld surface analysis (HS) and two-dimensional fingerprinting were used to enumerate the intermolecular interactions within the crystal. The results demonstrate that the H···Cl/Cl···H, O···H/H···O, and F···H/H···F interactions are the most significant. Full Interaction Maps (FIMs) analysis predicts the positions of hydrogen bond acceptors and donors, confirming the supramolecular arrangement observed in HFC.Cl. Computational modeling studies using the Bravais-Friedel, Donnay-Harker (BFDH), and Growth Morphology (GM) methods predict the morphology of the HFC.Cl crystal. Both approaches estimate a comparable crystal shape characterized by six principal facets. Density functional theory (DFT) calculations were conducted utilizing the DMol software to investigate the electronic structure and comprehensive reactivity features of HFC.Cl. The low HOMO energy suggests significant stability against electrophilic attacks, while the high HOMO-LUMO band gap indicates high chemical hardness. Fukui functions were also calculated to identify atomic sites susceptible to nucleophilic and electrophilic attacks. This study offers a comprehensive insight into the structural and electronic properties of HFC.Cl, offering valuable information for the development of new pharmaceutical compositions.
5-氟胞嘧啶（FC）具有一种复杂的固态结构，这给其药物研发带来了挑战。本文介绍了一种新型药用盐——氟胞嘧啶氯化物（HFC.Cl）的实验和理论研究。单晶X射线衍射（SCXRD）研究表明，HFC.Cl在单斜晶系和P2/c空间群中形成晶体。该结构由一系列氢键相互作用维持，包括N-H···Cl、N-H···O和C-H···F。此外，氯离子阴离子与HFC阳离子之间的非共价阴离子···π相互作用在建立三维网络中发挥作用。使用 Hirshfeld 表面分析（HS）和二维指纹图谱来列举晶体内的分子间相互作用。结果表明，H···Cl/Cl···H、O···H/H···O和F···H/H···F相互作用最为显著。全相互作用图（FIMs）分析预测了氢键受体和供体的位置，证实了在HFC.Cl中观察到的超分子排列。使用布拉维-弗里德尔、唐奈-哈克（BFDH）和生长形态（GM）方法的计算建模研究预测了HFC.Cl晶体的形态。两种方法都估计出具有六个主晶面的可比晶体形状。利用DMol软件进行密度泛函理论（DFT）计算，以研究HFC.Cl的电子结构和综合反应特性。低的最高占据分子轨道（HOMO）能量表明对亲电攻击具有显著稳定性，而高的HOMO-最低未占据分子轨道（LUMO）带隙表明具有高化学硬度。还计算了福井函数以识别易受亲核和亲电攻击的原子位点。本研究全面深入地了解了HFC.Cl的结构和电子性质，为新型药物组合物的开发提供了有价值的信息。
