Instituto Andaluz de Ciencias de la Tierra, Consejo Superior de Investigaciones Científicas-Universidad de Granada, Av. de las Palmeras, 4, 18100-Armilla, Granada, Spain.
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Ciudad de Mexico, 09340, México.
J Comput Aided Mol Des. 2022 Jul;36(7):549-562. doi: 10.1007/s10822-022-00465-2. Epub 2022 Jul 26.
Sulfonamides are an important class of therapeutic agents. The increase in the number of new sulfonamide derivatives makes it necessary to study more rationally the chemical structure, because the solid forms often display different mechanical, thermal and physicochemical properties that can influence the bioavailability and stability of the drugs; consequently, the polymorphic structures are of great interest to the pharmaceutical industry because of their ability to modify the physical properties of the active pharmaceutical ingredient. The molecular interactions of these drugs in their crystal lattice are important for the stability of the crystals and polymorphism and for preparing composite complexes for optimizing the use of these drugs. In this work, the crystal structure of these drugs and crystal polymorphism is investigated. So, the crystal forms of antibiotics derivatives of the sulfonamides, sulfamethoxazole, sulfamethazine, sulfachloropyridazine, and sulfacetamide are studied at the molecular and supramolecular level by using computational modeling approach at quantum mechanical level. The spectroscopic properties of these systems are also studied explaining assignments of previous experimental data. The results of DFT calculations reproduce the crystal structures of sulfonamides determined experimentally and the polymorphism in these molecules have been clarified. Likewise, the main intermolecular interactions in all crystal forms of these sulfonamides are H-bonds among the sulfonic and amino groups and SNH groups, and also some π-π interactions. Also, these 3-D periodical models allow the exploration of the intermolecular interactions included in the crystal structures and some of these interactions can alter the vibration modes of the molecules. Therefore, the use of these models can be useful for experimental spectroscopy studies where use actual crystal solids.
磺胺类药物是一类重要的治疗剂。新的磺胺衍生物数量的增加使得有必要更合理地研究其化学结构，因为固体形式通常表现出不同的机械、热和物理化学性质，这些性质会影响药物的生物利用度和稳定性；因此，多晶型结构对制药工业具有重要意义，因为它们能够改变活性药物成分的物理性质。这些药物在晶格中的分子相互作用对于晶体和多晶型的稳定性以及为优化这些药物的使用而制备复合配合物都是很重要的。在这项工作中，研究了这些药物的晶体结构和晶体多态性。因此，在量子力学水平上，通过使用计算建模方法，对磺胺类抗生素衍生物磺胺甲恶唑、磺胺二甲嘧啶、磺胺氯哒嗪和磺胺醋酰的晶体形式进行了分子和超分子水平的研究。还研究了这些体系的光谱性质，解释了以前实验数据的归属。DFT 计算的结果再现了实验确定的磺胺类药物的晶体结构，并阐明了这些分子中的多晶型现象。同样，这些磺胺类药物所有晶体形式中的主要分子间相互作用是磺酸基和氨基之间以及 SNH 基团之间的氢键，以及一些π-π相互作用。此外，这些三维周期性模型允许探索晶体结构中包含的分子间相互作用，这些相互作用中的一些可以改变分子的振动模式。因此，这些模型可用于实验光谱学研究，在实验中使用实际的晶体固体。
