Guillén Marilia, Mora Asiloé J, Belandria Lusbely M, Seijas Luis E, Ramírez Jeans W, Burgos José L, Rincón Luis, Delgado Gerzon E
Laboratorio de Cristalografía, Departamento de Química. Facultad de Ciencias, Universidad de Los Andes, Mérida, 5101, Venezuela.
Laboratorio de Procesos Dinámicos, Departamento de Química, Facultad de Ciencias, Universidad de Los Andes, Mérida, 5101, Venezuela.
Acta Crystallogr B Struct Sci Cryst Eng Mater. 2020 Dec 1;76(Pt 6):1077-1091. doi: 10.1107/S2052520620013773. Epub 2020 Nov 16.
4-Methylhippuric acid {systematic name: 2-[(4-methylbenzoyl)amino]ethanoic acid}, a p-xylene excreted metabolite with a backbone containing three rotatable bonds (R-bonds), is likely to produce more than one stable molecular structure in the solid state. In this work, we prepared polymorph I by slow solvent evaporation (plates with Z' = 1) and polymorph II by mechanical grinding (plates with Z' = 2). Potential energy surface (PES) analysis, rotating the molecule about the C-C-N-C torsion angle, shows four conformational energy basins. The second basin, with torsion angles near -73°, agree with the conformations adopted by polymorph I and molecules A of polymorph II, and the third basin at 57° matched molecules B of polymorph II. The energy barrier between these basins is 27.5 kJ mol. Superposition of the molecules of polymorphs I and II rendered a maximum r.m.s. deviation of 0.398 Å. Polymorphs I and II are therefore true conformational polymorphs. The crystal packing of polymorph I consists of C(5) chains linked by N-H...O interactions along the a axis and C(7) chains linked by O-H...O interactions along the b axis. In polymorph II, two molecules (A with A or B with B) are connected by two acid-amide O-H...O interactions rendering R(14) centrosymmetric dimers. These dimers alternate to pile up along the b axis linked by N-H...O interactions. A Hirshfeld surface analysis localized weaker noncovalent interactions, C-H...O and C-H...π, with contact distances close to the sum of the van der Waals radii. Electron density at a local level using the Quantum Theory of Atoms in Molecules (QTAIM) and the Electron Localization Function (ELF), or a semi-local level using noncovalent interactions, was used to rank interactions. Strong closed shell interactions in classical O-H...O and N-H...O hydrogen bonds have electron density highly localized on bond critical points. Weaker delocalized electron density is seen around the p-methylphenyl rings associated with dispersive C-H...π and H...H interactions.
4-甲基马尿酸{系统名称：2-[(4-甲基苯甲酰基)氨基]乙酸}，是对二甲苯的一种排泄代谢产物，其主链含有三个可旋转键（R键），在固态下可能会产生不止一种稳定的分子结构。在这项工作中，我们通过缓慢溶剂蒸发制备了多晶型物I（Z' = 1的片状晶体），并通过机械研磨制备了多晶型物II（Z' = 2的片状晶体）。通过围绕C-C-N-C扭转角旋转分子进行势能面（PES）分析，显示出四个构象能谷。第二个能谷的扭转角接近-73°，与多晶型物I和多晶型物II的分子A所采用的构象一致，第三个能谷在57°时与多晶型物II的分子B匹配。这些能谷之间的能垒为27.5 kJ mol。多晶型物I和II的分子叠加后的最大均方根偏差为0.398 Å。因此，多晶型物I和II是真正的构象多晶型物。多晶型物I的晶体堆积由沿着a轴通过N-H...O相互作用连接的C(5)链和沿着b轴通过O-H...O相互作用连接的C(7)链组成。在多晶型物II中，两个分子（A与A或B与B）通过两个酸-酰胺O-H...O相互作用连接，形成R(14)中心对称二聚体。这些二聚体交替排列，沿着b轴通过N-H...O相互作用堆积。Hirshfeld表面分析确定了较弱的非共价相互作用，即C-H...O和C-H...π，其接触距离接近范德华半径之和。使用分子中的原子量子理论（QTAIM）和电子定位函数（ELF）在局部水平上的电子密度，或使用非共价相互作用在半局部水平上的电子密度，来对相互作用进行排序。经典O-H...O和N-H...O氢键中的强闭壳层相互作用在键临界点处具有高度局域化的电子密度。在与分散的C-H...π和H...H相互作用相关的对甲基苯基环周围可以看到较弱的离域电子密度。
