Synthesis, Spectroscopic, Calculated and Thermal Study of Copper and Cobalt Complexes with Dacarbazine

Abstract

: Dacarbazine, DAC, 5-(3,3-dimethyltriazeno)imidazol-4-carboxamideis is an imidazole-carboxamide derivative, that is structurally related to purines. DAC belongs to the triazene compounds, which are a group of alkylating agents with antitumour and mutagenic properties. DAC is a non-cell cycle specific drug, active on all phases of cellular cycle. In the frame of this work the 3d-metal complexes (cobalt and copper) with dacarbazine were synthesized. Their spectroscopic properties by the use of FT-IR, FT-Raman and 1HNMR were studied. The structures of dacarbazine and its complexes with copper(II) and cobalt(II) were calculated using DFT methods. The effect of metals on the electronic charge distribution of dacarbazine was discussed on the basis of calculated NBO atomic charges. The reactivity of metal complexes in relation to ligand alone was estimated on the basis of calculated energy of HOMO and LUMO orbitals. The aromaticity of imidazole ring in dacarbazine and the complexes was compared (on the basis of calculated geometric indices of aromaticity). Thermal stability of the investigated 3d-metal complexes with dacarbazine and the products of their thermal decomposition were analyzed.

Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation

“…FT-IR spectra of unmodified DTIC and their multicomponent crystals are shown in Figure S5. For band assignments (Table S6) and spectra interpretation, we rely on the crystallographic description (Section ) and reference spectroscopic data available for DTIC-related compounds. ,, DTIC exhibits typical infrared stretching frequencies at 3380 and 3170 cm –1 (amide N–H stretches), 1655 cm –1 (amide CO stretch), and 1608 cm –1 (CC stretch). Salt/cocrystal formations have been proved by verification of these characteristic API vibrational modes, mainly due to the emergence of new absorption bands at around 1700 cm –1 in the DTIC multicomponent crystal FT-IR spectra.…”

“…The 1 H NMR experiments certified the stoichiometry of the DTIC:coformer through integral values and further ascertained the sample purity in solution. Assignments of proton chemical shifts and spectra interpretation were performed using DTIC 1 H NMR spectra reported in the literature. ,, Hence, the 1 H NMR spectra of DTIC salt/cocrystal forms (see Figures S7–S11) displayed the predicted DTIC signals and also the typical signals, e.g., CH (olefinic) and −CH 2 (methylene), of the carboxylic acid molecules that are absent in the DTIC 1 H NMR spectrum (Figure S6). The absence of unassigned proton signals in the 1 H NMR spectra reinforces the purity of the synthesized crystals.…”

“…Assignments of proton chemical shifts and spectra interpretation were performed using DTIC 1 H NMR spectra reported in the literature. 35,41,42 Hence, the Likewise, the DTIC-HOXA DSC curve is also featured by a single degradation exothermic peak centered at 175.0 °C (T onset = 170.2 °C). This unique thermal event agrees with the mass loss that occurs in the TG curve, beginning at around 166 °C (T onset = 161.7 °C).…”