Department of Physics, University of Lucknow, Lucknow 226 007, Uttar Pradesh, India.
Centre for Pharmaceutical Engineering Science and School of Pharmacy and Medical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
Spectrochim Acta A Mol Biomol Spectrosc. 2019 Oct 5;221:117170. doi: 10.1016/j.saa.2019.117170. Epub 2019 May 28.
Cocrystal monohydrate of nitrofurantoin (NF) with melamine (MELA) has been studied as NF is an antibacterial drug used for the treatment of urinary tract infections. The structure of nitrofurantoin-melamine-monohydrate (NF-MELA-HO) is characterized by FT-IR and FT-Raman spectroscopy. The energies and vibrational frequencies of the optimized structures calculated using quantum chemical calculations. Supported by normal coordinate analyses and potential energy distributions (PEDs), the complete vibrational assignments recommended for the observed fundamentals of cocrystal hydrate. With the aim of inclusion of all the H-bond interactions, dimer of NF-MELA-HO has been studied as only two molecules of cocrystal hydrate are present in the unit cell. By the study of dimeric model consistent assignment of the FT-IR and FT-Raman spectrum obtained. H-bonds are of essential importance in an extensive range of molecular sciences. The vibrational analyses depict existence of H-bonding (O-H⋯N) between water O-H and pyridyl N atom of MELA in both monomer and dimer. To probe the strength and nature of H-bonding in monomer and dimer, topological parameters such as electron density (ρ), Laplacian of electron density (∇ρ), total electron energy density (H) and H-bond energy (E) at bond critical points (BCP) are evaluated by quantum theory of atoms in molecules (QTAIM). Natural bond orbitals (NBOs) analyses are carried out to study especially the intra and intermolecular H-bonding and their second order stabilization energy (E). The value of HOMO-LUMO energy band gap for NF-MELA-HO (monomer and dimer both) is less than NF, showing more chemical reactivity for NF-MELA-HO. Chemical reactivity has been described with the assistance of electronic descriptors. Global electrophilicity index (ω = 7.3992 eV) shows that NF-MELA-HO behaves as a strong electrophile than NF. The local reactivity descriptors analyses such as Fukui functions, local softnesses and electrophilicity indices performed to determine the reactive sites within NF-MELA-HO. In MEP map of NF-MELA (monomer and dimer) electronegative regions are about NO and C=O group of NF, although the electropositive regions are around NH, N-H group and HO molecule. Molar refractivity (MR) value of NF-MELA-HO (monomer and dimer) lies within the range set by Lipinski's modified rules. This study could set as an example to study the H-bond interactions in pharmaceutical cocrystals.
硝呋太尔与三聚氰胺共晶一水合物的结构已被研究，因为硝呋太尔是一种用于治疗尿路感染的抗菌药物。硝呋太尔-三聚氰胺-一水合物（NF-MELA-HO）的结构通过傅里叶变换红外光谱（FT-IR）和傅里叶变换拉曼光谱（FT-Raman）进行了表征。使用量子化学计算对优化结构的能量和振动频率进行了计算。通过正则坐标分析和势能分布（PED）的支持，为观察到的共晶水合物的基本振动分配了完整的振动分配。为了包括所有氢键相互作用，研究了 NF-MELA-HO 的二聚体，因为在晶胞中只有两个共晶水合物分子。通过对二聚体模型的研究，对获得的 FT-IR 和 FT-Raman 光谱进行了一致的分配。氢键在广泛的分子科学中具有重要意义。振动分析表明，在单体和二聚体中，水 O-H 和三聚氰胺的吡啶 N 原子之间存在氢键（O-H⋯N）。为了探究单体和二聚体中氢键的强度和性质，通过分子中的原子量子理论（QTAIM）评估了键临界点（BCP）处的电子密度（ρ）、电子密度的拉普拉斯（∇ρ）、总电子能量密度（H）和氢键能量（E）等拓扑参数。进行自然键轨道（NBO）分析以研究特别是分子内和分子间氢键及其二阶稳定化能（E）。NF-MELA-HO（单体和二聚体）的 HOMO-LUMO 能带隙值小于 NF，表明 NF-MELA-HO 具有更高的化学反应活性。借助电子描述符描述了化学反应性。全局亲电性指数（ω=7.3992 eV）表明，NF-MELA-HO 比 NF 表现出更强的亲电性。进行了局部反应性描述符分析，例如福井函数、局部软度和亲电指数，以确定 NF-MELA-HO 中的反应位点。在 NF-MELA（单体和二聚体）的 MEP 图中，电负性区域位于 NF 的 NO 和 C=O 基团附近，尽管正电性区域位于 NH、N-H 基团和 HO 分子附近。NF-MELA-HO（单体和二聚体）的摩尔折射度（MR）值在 Lipinski 修改规则规定的范围内。这项研究可以作为研究药物共晶中氢键相互作用的范例。
