First Bivalent Palladium and Platinum Cyanoximates: Synthesis, Characterization, and Biological Activity
A series of five cyanoximes (compounds having the general formula NC−C(NOH)−R, where R is an amide or carboxylic ester group) have been synthesized and spectroscopically and structurally characterized. These are 2-cyano-2-isonitrosoacetamide (later HACO), 2-cyano-2-isonitrosothioacetamide (HTCO), 2-cyano-2-isonitrosoethylacetate (HECO), 2-cyano-2-isonitroso-N-piperidinylacetamide (HPiPCO), and 2-cyano-2-isonitroso-N-morpholinylacetamide (HMCO). A high yield method of synthesis was developed for the last two previously unknown amidocyanoximes. Variable temperature 13C NMR studies in DMSO-d6 solutions allowed the determination of rotational energy barriers for these two new cyanoximes. The HPiPCO and HMCO oxime molecules adopt a trans-anti configuration in the solid state according to X-ray analysis. Reactions between aqueous solutions of K+L- (L = cyanoximate anions: TCO-, PiPCO-, and MCO-) and K2[MCl4] (M = Pd, Pt) resulted in the formation of ML2 complexes. The crystal structure of Pd(MCO)2·DMSO was determined and showed the formation of coplanar dimeric [Pd(MCO)]2 units with 3.13 Å Pd···Pd separation. The complex adopts cis geometry with anions being in the nitroso form. In the presence of bivalent Pd and Pt, ACO- and ECO- anions completely or partially hydrolyze in aqueous solutions to the dianion of 2-cyano-2-isonitrosoacetic acid (AACO2-). The crystal structure of the product of the hydrolysis reaction, K2[Pd(AACO)2]·4H2O, was determined. Data revealed planar and cis geometry of the [Pd(AACO)2]2- anion where cyanoximes are in the nitroso form and adopt a cis-anti configuration. All synthesized cyanoxime ligands and nine of their Pd(II) and Pt(II) complexes were tested in vitro on antiproliferating activity using human cervical cancer HeLa cell lines, and cisplatin as a positive control substance. Two out of the nine studied complexes, Pd(MCO)2 and Pt(MCO), were found to be active compounds inflicting death on 28% and 16% of the cells, respectively, with 55% value for the cisplatin under the same conditions.