Novel flucytosine salt: Structure, Hirshfild surface analysis, morphology, FIMs, and computational studies

IF 2.7 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling Pub Date : 2025-03-12 DOI:10.1016/j.jmgm.2025.109012

Hela Ferjani

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引用次数: 0

Abstract

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 P2₁/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 DMol³ 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.

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来源期刊

Journal of molecular graphics & modelling 生物-计算机：跨学科应用

CiteScore

5.50

自引率

6.90%

发文量

216

审稿时长

35 days

期刊介绍： The Journal of Molecular Graphics and Modelling is devoted to the publication of papers on the uses of computers in theoretical investigations of molecular structure, function, interaction, and design. The scope of the journal includes all aspects of molecular modeling and computational chemistry, including, for instance, the study of molecular shape and properties, molecular simulations, protein and polymer engineering, drug design, materials design, structure-activity and structure-property relationships, database mining, and compound library design. As a primary research journal, JMGM seeks to bring new knowledge to the attention of our readers. As such, submissions to the journal need to not only report results, but must draw conclusions and explore implications of the work presented. Authors are strongly encouraged to bear this in mind when preparing manuscripts. Routine applications of standard modelling approaches, providing only very limited new scientific insight, will not meet our criteria for publication. Reproducibility of reported calculations is an important issue. Wherever possible, we urge authors to enhance their papers with Supplementary Data, for example, in QSAR studies machine-readable versions of molecular datasets or in the development of new force-field parameters versions of the topology and force field parameter files. Routine applications of existing methods that do not lead to genuinely new insight will not be considered.