Measurement and Correlation of the Solubility of Pyrimethanil in Seven Monosolvents and Two Different Binary Mixed Solvents

The solubility of pyrimethanil in two binary solvents (water + methanol and water + ethanol) and seven monosolvents (methanol, ethanol, <i>n</i>-propanol, isopropanol, <i>n</i>-butanol, isobutanol, and cyclohexane) was measured by a gravimetric method within the temperature range of 283.15 to 323.15 K at atmospheric pressure. In the investigated temperature range, the solubility of pyrimethanil in all monosolvents or mixed solvents increases with increasing temperature. The solubility in the monosolvents was well-correlated using the NRTL model, the Apelblat model, and the Wilson model. Furthermore, the NRTL model and the modified version of the Jouyban–Acree model (the Apel-JA equation) were employed to correlate the solubility in binary solvents. The results showed that these models have a satisfactory correlation. When we measured the solubility, we found that the solvent has a great influence on the crystal habit. Therefore, these results can give guidance for practical industrial processes such as the design of the crystallization process and control of the crystal morphology

Solubility Measurement and Correlation of Fosfomycin Sodium in Six Organic Solvents and Different Binary Solvents at Temperatures between 283.15 and 323.15 K

The solubility data of fosfomycin sodium (FOM-Na) in six pure solvents (methanol, ethanol, propanol, cyclohexane, acetone, <i>N</i>,<i>N</i>-dimethylformamide) and two binary solvents (methanol + ethanol, methanol + acetone) at temperatures ranging from 283.15 to 323.15 K were measured by a laser monitoring dynamic method at atmospheric pressure. It turned out that the solubility data decreased with increasing temperature, and also varies with the composition of the solvents. Moreover, the experimental data in pure solvents have been correlated with two thermodynamic models (i.e., modified Apelblat and van’t Hoff), and the data in binary solvents have been correlated with CNIBS/R-K equation and two modified versions of Jouyban–Acree models (Van’t-JA equation and Apel-JA equation), respectively. All the results showed a good agreement with the experimental data. Intermolecular interaction force and dielectric constants are introduced to explain the relationship between solubility and temperature. In addition, the analysis of the solubilities implies that higher temperature may destroy the forces between the solvent and solute molecules, leading to lower solubility. And this can give a guide to the design and optimization of the crystallization process of FOM-Na in the industry

“Mind the Gap”: Raman Evidence for Rapid Inactivation of CTX-M‑9 β‑Lactamase Using Mechanism-Based Inhibitors that Bridge the Active Site

CTX-M β-lactamases are one of the fastest growing extended-spectrum β-lactamase (ESBL) families found in <i>Escherichia coli</i> rendering this organism extremely difficult to treat with β-lactam antibiotics. Although they are grouped in class A β-lactamases, the CTX-M family possesses low sequence identity with other enzymes. In addition, they have high hydrolytic activity against oxyimino-cephalosporins, despite having smaller active sites compared to other ESBLs in class A. Similar to most class A enzymes, most of the CTX-M β-lactamases can be inhibited by the clinical inhibitors (clavulanic acid, sulbactam, and tazobactam), but the prevalence of inhibitor resistance is an emerging clinical threat. Thus, the mechanistic details of inhibition pathways are needed for new inhibitor development. Here, we use Raman microscopy to study the CTX-M-9 inactivation reaction with the three commercially available inhibitors and compare these findings to the analysis of the S130G variant. Characterization of the reactions in CTX-M-9 single crystals and solution show the formation of a unique cross-linked species, probably involving Ser70 and Ser130, with subsequent hydrolysis leading to an acrylate species linked to Ser130. In solution, a major population of this species is seen at 25 ms after mixing. Support for this finding comes from the CTX-M-9 S130G variant that reacts with clavulanic acid, sulbactam, and tazobactam in solution, but lacks the characteristic spectroscopic signature for the Ser130-linked species. Understanding the mechanism of inactivation of this clinically important ESBL-type class A lactamase permits us to approach the challenge of inhibitor resistance using knowledge of the bridging species in the inactivation pathway