SYNTHESIS AND CHARACTERIZATION OF A SERIES OF ACHIRAL AND CHIRAL MONO[(DIEN)PT(II)I]I AND BIS[(DIEN)PT(II)I]I DERIVATIVES AS POTENTIAL DNA AND RNA STRUCTURE PROBES AND ANTICANCER DRUGS

This paper reports the design, synthesis, and characterization of a series of achirally and chirally substituted diethylenetriamine (dien) and bis(dien) complexes of Pt(II) for study as potential nucleic acid structure and conformation probes. Chiral diisopropyl and achiral tetramethyl derivatives of [(dien)Pt(II)III, complexes R- and S-1b-d, were designed to discriminate between B and Z conformations of DNA. Bis([(dien)Pt(II)IJI) complexes with variable length (n) methylene linkers, 3a (n = 2-9), and selected chiral tetraisopropyl derivatives, R- and S-3b (n = 3,9), were designed to probe the relationship between linker length and steric substitution on the conformation and structure selectivity of interstrand nucleic acid cross-linking. The Pt(II) complexes were prepared from the corresponding amine ligands in almost quantitative yield by a one step synthesis utilizing Pt(DMSO)2I2. The diisopropyldien ligands R- and S-1 lb were prepared by a general route in high overall yield from both enantiomers of the amino acid valine via the enantiomeric N-tosylisopropylaziridines R- and S-8b. The tetramethyldien ligand 11c was prepared by the same route starting from the commercially available dimethylaminoethanol 6c. Bis(dien) ligands, 13a (n = 2-9), in which two dien ligands are linked via the central amine to a variable length linker of two to nine methylene groups were synthesized in high overall yield from N-tosylaziridine and the corresponding 1,n-diaminoalkane. Bis(diisopropyldien) ligands, R- and S-13b (n = 3, 9), were similarly prepared from the corresponding N-tosylisopropylaziridines. Selected Pt(II) analogs of the Pt(II) complexes were prepared via Pd(DMSO)2Cl2.