The dinuclear zinc complex [Zn₂{bcmp(-H)}(μ-Cl)](ClO₄)₂·H₂O {bcmp = 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol} has been synthesized and structurally characterized. The DNA binding affinity was assessed by ethidium bromide fluorescence quenching experiments. The complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration. Mechanistic studies were carried out using the DNA and RNA models bis(2,4-dinitrophenyl) phosphate (BDNPP) and 2-hydroxypropyl p-nitrophenyl phosphate (HPNP). A detailed kinetic analysis suggested that the bridging OH group of the solution species [Zn₂{bcmp(-H)}(μ-OH)]²⁺ acts as the nucleophile in the hydrolysis of BDNPP, while in the case of HPNP, the bridging OH group acts as a general base and seems to shift to a terminal position upon substrate coordination. Finally, the cytotoxicity profile of the dinuclear zinc(II) complex was assessed. The complex showed promising in vitro antitumour activity against pancreatic and lung cancers cell lines.

Invited for the cover of this issue are researchers from the National University of Ireland, Galway, and the University of Padua, Italy. The cover image shows the X-ray structure of the dinuclear bis(1,4,7-triazacyclononane) zinc complex synthesized in this work. The complex converts supercoiled plasmid DNA into the nicked form at low micromolar concentration and shows promising in vitro antitumor activity against pancreatic and lung cancer cell lines.

The effects of ball-milling and cryomilling on sulfamerazine forms I and II (SMZ FI, FII) were investigated using X-ray powder diffraction, infrared and near-infrared (NIR) spectroscopy. Cryomilling resulted in a complete amorphization of both polymorphs. Milling at room temperature gave mixtures of amorphous SMZ (FA) and FII. Calibration models were developed for the quantitative analysis of binary (FI/FII, FI/FA, and FII/FA) and ternary (FI/FII/FA) mixtures using NIR spectroscopy combined with partial least-squares (PLS) regression. The PLS models for binary (0%–100%), ternary (0%–100%), and low-level (0%–10%) binary mixtures had root-mean-square errors of prediction of ≤1.8%, ≤5.1%, and ≤0.80%, respectively. The calibration models were used to obtain a detailed quantitative picture of solid-state transformations during milling and any subsequent recrystallizations. FA prepared by cryomilling FI for less than 60 min recrystallized to mixtures of FI and FII, whereas samples milled for more than 60 min crystallized to pure FII. The effect of comilling SMZ with stoichiometric amounts of additives was investigated. SMZ formed amorphous materials with oxalic, dl-tartaric, and citric acids that were more stable toward recrystallization than FA. Amorphous SMZ/oxalic acid was found to recrystallize to a 2:1 cocrystal during storage. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci

The formation and physical stability of amorphous sulfathiazole obtained from polymorphic forms I and III by cryomilling was investigated by X-ray powder diffraction (XRPD) and near-infrared (NIR) spectroscopy. Principal component analysis was applied to the NIR data to monitor the generation of crystalline disorder with milling time and to study subsequent recrystallization under different storage conditions. Complete conversion into the amorphous phase was observed for both forms after 45 (form I) and 150 min (form III) milling time. Upon storage under vacuum over silica gel for 14 days at 4°C, amorphous samples remained amorphous. However, under the same conditions at ambient temperature, recrystallization occurred. Amorphous samples obtained from form I had crystallized back to the original polymorph, whereas those prepared from form III had partially crystallized to mixtures of polymorphs. Amorphous samples stored at ambient temperature and humidity absorbed moisture, which facilitated crystallization to a mixture of polymorphs in both cases. Quantitative analyses of amorphous content in binary mixtures with forms I and III were carried out by XRPD and NIR spectroscopy combined with partial least squares regression. The calibration models had root mean square error of prediction values of <2.0% and were applied to quantify the extent of crystalline disorder during cryomilling. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:93–103, 2013