Synthesis, structures and antitumor activity of the first crown ester-linked bipyridyl platinum complexes

Three new crown ester-linked bipyridine homologs with three, four or five e thylene glycol units, which are bulky and soluble in both hydrophilic and l ipophilic;media, were synthesized. The reaction of the appropriate macrocyc les with K2PtCl4 in water gave yellow cisplatin analogs in good yield. Thes e complexes were converted to carboplatin analogs by exchange of the leavin g group. All the compounds were characterized by elemental analysis and var ious spectroscopic methods. Carboplatin analogs showed good solubility in b oth hydrophilic and lipophilic media. The crystal structure of 2c, the carb oplatin analog with macrocycles containing five ethylene glycol units, was determined by X-ray diffraction: space group P (1) over bar, a = 9.798(1), b = 12.580(3), c = 13.945(2) Angstrom, alpha =108.61(2), beta = 94.59(1), g amma = 97.42(2)degrees, Z = 2, R = 0.0618. Some of platinum complexes Showe d a moderate cytotoxic effect on both murine leukemia L1210 and P388 even t hough they do not have any NH proton. (C) 1999 Elsevier Science Inc. All ri ghts reserved.