Design, synthesis, characterizing and DFT calculations of a binary CT complex co-crystal of bioactive moieties in different polar solvents to investigate its pharmacological activity

Imidazole (IM) and salicylic acid (SA) have a significant class among the medical compound. These are widely used as topical drugs like antifungal, antibacterial, anticancer, immunosuppressive agent, etc. These two bioactive organic moieties are combined by a weak hydrogen bond formed by hydrogen transfer. The charge transfer (CT) complex of acceptor (SA) and donor (IM), has been synthesized at room temperature in methanol and confirmed by signal-crystal XRD, conductance and UV–visible spectroscopy. The X-ray crystallography provides the original structural information of CT complex and displays the existence of N⁺—H––O^– bond between IM and SA. The physical properties such as (<i>E_CT</i>), (<i>R_N</i>), (<i>I_D</i>), (<i>f</i>), (<i>D</i>) and (Δ G⁰) along with molar extinction coefficient (<i>ε_CT</i>) and formation constant (<i>K_CT</i>) were estimated through UV–visible spectroscopy. Job’s method and Benesi-Hildebrand equation suggested 1:1 stoichiometry of ([IM]⁺[SA]⁻). The results indicate a complete transfer of hydrogen atom and CT complex formation with 1:1 molar ratio of IM and SA. Antimicrobial activity was veiled against different bacteria like <i>Escherichia coli, Bacillus subtilis</i> and <i>Staphylococcus aureus</i>; and different fungi as <i>Fusarium oxysporum, Candida albicans</i> and <i>Aspergillus niger</i> by disc diffusion method. CT complex was also tested for cytotoxic activity against lung cancer cell lines in comparison to breast cancer cell lines. Molecular docking provides the information of binding of [(IM)⁺(SA)⁻] with the cancer marker (1M17), which has substantial application for drug designing. The investigational studies were supplemented through time-dependent density functional theory (TD-DFT) using basis set B3LYP/6-311G**. Through DFT calculations, HOMO→LUMO electronic energy gap (ΔE) was obtained. A new organic charge transfer complex co-crystal has been prepared, characterized and explored for, Antioxident, Anticancer, antibacterial and antifungal activities. The experimental results are supported by theoretical analysis. Communicated by Ramaswamy H. Sarma

咪唑（Imidazole，IM）与水杨酸（Salicylic Acid，SA）属于一类重要的医用化合物，二者被广泛用作外用药物，涵盖抗真菌、抗菌、抗肿瘤、免疫抑制等多种功效。这两种生物活性有机基团通过氢转移形成的弱氢键相结合。以水杨酸为受体、咪唑为供体的电荷转移（Charge Transfer，CT）配合物，于室温下在甲醇中合成，并通过单晶X射线衍射（Single-Crystal XRD）、电导法与紫外-可见光谱法进行了表征确认。X射线晶体学分析获取了该CT配合物的原始结构信息，证实了咪唑与水杨酸之间存在N⁺—H∙∙∙O⁻氢键。通过紫外-可见光谱法测定了多项物理性质，包括电荷转移能（<i>E_CT</i>）、氮原子相关参数（<i>R_N</i>）、供体电离势（<i>I_D</i>）、振子强度（<i>f</i>）、偶极矩（<i>D</i>）、标准吉布斯自由能变（ΔG⁰），以及摩尔消光系数（<i>ε_CT</i>）和配合物形成常数（<i>K_CT</i>）。乔氏法（Job’s Method）与贝内西-希尔德布兰德方程（Benesi-Hildebrand Equation）的分析结果表明，该配合物的化学计量比为1:1，即([IM]⁺[SA]⁻)。实验结果证实氢原子发生了完全转移，且咪唑与水杨酸以1:1的摩尔比形成了CT配合物。采用纸片扩散法测试了该配合物的抗菌活性，受试菌株包括大肠杆菌（<i>Escherichia coli</i>）、枯草芽孢杆菌（<i>Bacillus subtilis</i>）与金黄色葡萄球菌（<i>Staphylococcus aureus</i>）等细菌，以及尖孢镰刀菌（<i>Fusarium oxysporum</i>）、白色念珠菌（<i>Candida albicans</i>）与黑曲霉（<i>Aspergillus niger</i>）等真菌。同时，该CT配合物还以乳腺癌细胞系为对照，测试了其对肺癌细胞系的细胞毒性活性。分子对接（Molecular Docking）分析揭示了[(IM)⁺(SA)⁻]与癌症标志物1M17的结合模式，该结果可为药物设计提供重要参考。本研究的实验数据通过含时密度泛函理论（Time-Dependent Density Functional Theory，TD-DFT）结合基组B3LYP/6-311G**进行了补充验证。通过密度泛函理论（DFT）计算，得到了最高占据分子轨道（Highest Occupied Molecular Orbital，HOMO）与最低未占据分子轨道（Lowest Unoccupied Molecular Orbital，LUMO）的电子能隙（ΔE）。本研究制备并表征了一种新型有机电荷转移配合物共晶体，并对其抗氧化、抗肿瘤、抗菌及抗真菌活性进行了探究。实验结果与理论分析结果具有良好的一致性。由Ramaswamy H. Sarma转交。