Salt Cocrystal and Salt of Marbofloxacin with Butenedioic Acid: Impact of <i>cis</i>–<i><i>trans</i></i> Isomerism of Coformer on the Conformation and Properties of Marbofloxacin

Based on the study of the effect of positional isomerism of coformer functional groups on the cocrystallization and physicochemical properties of the active pharmaceutical ingredients, the impact of cis–trans isomeric butenedioic acid as coformers on the conformation, crystal structure, and its physicochemical properties of marbofloxacin was further explored. In this work, fumaric acid (FA) and maleic acid (MA) with different configurations were chosen as coformers to synthesize the pharmaceutical salt cocrystal (MBF-FA-H2FA) and salt (MBF-MA) of marbofloxacin (MBF), and their structures were fully characterized. Significant differences between the conformations of marbofloxacin in the salt cocrystal and in salt were found. In the salt cocrystal, the N atom of the piperazine group from marbofloxacin is coplanar with the pyridone ring, and the whole is straight like fumaric acid, whereas the marbofloxacin piperazine group in the salt is bent like the maleic acid configuration. Furthermore, the conformational variability of marbofloxacin in the salt cocrystal and the salt resulted in different crystal structures and opposite physicochemical properties. Notably, both multicomponent crystals have a surface hydrophilic intercalation structure. However, the salt cocrystal and salt exhibited different solubility and permeability. Specifically, the MBF-MA salt showed improved solubility and permeability, while the MBF-FA-H2FA salt cocrystal showed a decreased solubility and permeation rate compared to MBF. In addition, in vitro bacterial inhibitory activity assays indicated that the MBF-MA salt has stronger inhibitory activity against Gram-negative and Gram-positive bacterial strains than the MBF-FA-H2FA salt cocrystal and pure MBF

Coordination Field Tuned Cyanide-Bridged Polynuclear and One-Dimensional Heterobimetallic Complexes: Synthesis, Crystal Structures, and Magnetic Properties

Two mononuclear seven-coordinated macrocycle manganese­(II) compounds and four polycyanometallates containing different cyanide groups have been employed as building blocks to assemble cyanide-bridged heterobimetallic complexes, resulting in eight cyanide-bridged Fe^III/II-Mn^II and M^IV-Mn^II (M = Mo, W) complexes {[Mn­(L¹)]­[Fe­(1-MeIm)­(CN)₅]}_<i>n</i> (<b>1</b>), {[Mn­(L²)­(H₂O)]­[Fe­(1-MeIm)­(CN)₅]}­·2H₂O (<b>2</b>), {[Mn­(L¹)­(H₂O)]­[Mn­(L¹)]­[Fe­(CN)₆]}_<i>n</i>­·<i>n</i>(CH₄O)­·3.5<i>n</i>H₂O (<b>3</b>), {[Mn­(L²)­(H₂O)]₂]­[Fe­(CN)₆]}­·11H₂O (<b>4</b>), {[Mn­(L¹)­(H₂O)]­[Mn­(L¹)]­[Mo­(CN)₈]}_<i>n</i>­·4<i>n</i>H₂O (<b>5</b>), {[Mn­(L²)­(H₂O)]₂]­[Mo­(CN)₈]}­·3.5H₂O (<b>6</b>), {[Mn­(L¹)­(H₂O)]­[Mn­(L¹)]­[W­(CN)₈]}_<i>n</i>­·5<i>n</i>H₂O (<b>7</b>), {[Mn­(L²)­(H₂O)]₂]­[W­(CN)₈]}­·3H₂O (<b>8</b>). (L¹ = 3,6-diazaoctane-1,8-diamine, L² = 3,6-dioxaoctano-1,8-diamine). Single X-ray analysis reveals that complexes <b>1</b>, <b>3</b>, <b>5</b>, and <b>7</b> obtained by using [Mn­(L¹)]²⁺ as assemble segment can be structurally characterized as a one-dimensional coordination polymer, while the structures of the complexes <b>2</b>, <b>4</b>, <b>6</b>, and <b>8</b> with [Mn­(L²)]²⁺ as the ancillary compound belong to polynuclear entities, indicating that the different coordination field of the N atom or the O atom in the macrocyclic ligands can have an obvious influence on the structure types of the target complexes. Investigation of magnetic properties of complexes <b>1</b> and <b>2</b> showed the antiferromangetic coupling between the cyanide-bridged low-spin Fe­(III) ion and Mn­(II) ion. Additional, the weak magnetic interaction between the Mn­(II) ions bridged by diamagnetic cyanide building blocks can be found in other complexes

Microsomal Glutathione Transferase 1 Protects Against Toxicity Induced by Silica Nanoparticles but Not by Zinc Oxide Nanoparticles

Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO₂, CeO₂, SiO₂, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO₂ and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO₂ and CeO₂. We also noted pronounced cytotoxicity for three out of four additional SiO₂ nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO₂ nanoparticles tested and for one of the supplementary SiO₂ nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO₂ nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn²⁺ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn²⁺ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO₂ nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum