Synthesis and Characterization of a Series of Achiral and Chiral Mono 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 di-ethylenetriamine (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)I]I, complexes R- and S-lb-d, were designed to discriminate between B and Z conformations of DNA. Bis([(dien)Pt(II)I]I) 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 diiso-propyldien ligands R and S-1lb 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 lie 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)₂C1₂.