ABSTRACT
The thermal properties of three matrix metalloproteinase (MMP) inhibitors were investigated using a variety of instrumental methods. Differential scanning calorimetry revealed highly exothermic processes for all compounds above 200°C, and thermogravimetric analysis resulted in significant step-wise weight losses at the temperatures corresponding to the exothermic transitions. Hot stage microscopy observations for several compounds showed evolution of gas bubbles from crystals at temperatures that correlated with the exotherms. Thermal decomposition involving the hydroxamic acid functional group was suspected and further evaluated using various analytical techniques including reversed-phase HPLC, LC-MS-MS, TGA-FTIR and NMR. The mechanism proposed in the thermal decomposition involves a Lossen Rearrangement to form a dimeric species containing a urea linkage.
Subject(s)
Dimerization , Hot Temperature , Matrix Metalloproteinase Inhibitors , Calorimetry, Differential Scanning , Chromatography, High Pressure Liquid , Chromatography, Liquid , Magnetic Resonance Spectroscopy , Matrix Metalloproteinases/chemistry , Models, Chemical , Spectroscopy, Fourier Transform Infrared , Tandem Mass Spectrometry , Technology, Pharmaceutical , Temperature , ThermogravimetryABSTRACT
We have studied temperature dependent IR spectra of the C-H stretching modes of the imidazolium ring in [bmim][PF(6)], [bmim][Tf(2)N], [emim][Tf(2)N], [hmim][Tf(2)N], and [bmim][BF(4)]. Temperatures in this study are from 278 to 348 K at an interval of 10 K. Spectra of the C-H stretching modes have been deconvoluted using our previous computer program of the Voigt-lineshape function. Frequency shifts, Lorentzian spectral widths, and band absorbance were examined as a function of temperature. In order to interpret the observed behaviors, we have developed a simple mechanical model as well as a chemical equilibrium model. The model analyses suggest that enthalpy changes for the cluster and/or ion-pair breaking reactions in the liquid state are several kJ mol(-1) endothermic, and the degree of dissociations of ion pairs or hydrogen bonded clusters is in the range from 0.3 to 0.9 with different magnitudes for the five ionic liquids.