Nothenberg M S, Takeda G K, Najjar R
Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil.
J Inorg Biochem. 1991 May 15;42(3):217-29. doi: 10.1016/0162-0134(91)84008-w.
Adducts of several rhodium(II) carboxylates with two antiparasitic nitroimidazole ligands were prepared and characterized by elemental microanalysis, thermogravimetry, spectrophotometry (IR, UV, and visible), and proton magnetic resonance. Results of elemental and thermogravimetric analyses were consistent with the general formula Rh2(RCOO)4. 2L (R = aliphatic or aromatic carboxylic groups; L = metronidazole or benznidazole). The reddish-brown color of the adducts as well as their visible spectra suggest axial coordination of the nitroimidazole ligands through nitrogen atoms. NMR spectra indicate N3 as the coordinating atoms. Screening tests performed on cultures of T. cruzi indicate that aliphatic complexes--particularly propionate and acetate adducts--were more active than their aromatic counterparts, the same being observed with benznidazole adducts in relation to their metronidazole analogues. Evaluated for their usefulness as transfusion prophylactic agents against Chagas' disease, propionate derivatives failed to sterilize T. cruzi infected blood. An oral toxicity assay in mice showed mild toxic effects with daily doses of 5 mg/kg for 20 days.
制备了几种铑（II）羧酸盐与两种抗寄生虫硝基咪唑配体的加合物，并通过元素微量分析、热重分析、分光光度法（红外、紫外和可见）以及质子磁共振对其进行了表征。元素分析和热重分析结果与通式Rh2(RCOO)4·2L一致（R = 脂肪族或芳香族羧基；L = 甲硝唑或苯硝唑）。加合物的红棕色以及它们的可见光谱表明硝基咪唑配体通过氮原子进行轴向配位。核磁共振光谱表明配位原子为N3。对克氏锥虫培养物进行的筛选试验表明，脂肪族配合物——特别是丙酸盐和乙酸盐加合物——比它们的芳香族对应物更具活性，苯硝唑加合物相对于其甲硝唑类似物也观察到了同样的情况。对丙酸衍生物作为预防恰加斯病输血预防剂的有效性进行评估时，发现其未能使感染克氏锥虫的血液灭菌。在小鼠中进行的口服毒性试验表明，每日剂量为5 mg/kg，持续20天会产生轻微毒性作用。
