Platinum (II) and
platinum (IV)
coordination complexes derived from beta-silyl-substituted
amines were prepared. The solubility of selected complexes in water and physiological saline was measured, and the effect of the beta-
silicon on the reactivity of the complex in aqueous
solution was determined by HPLC. The stabilities of selected silyl complexes were compared to the
carbon analogues. The cyclic complexes 2a ("
silaplatin") and its Pt(IV) analogue, 2b, were very active against
L1210 leukemia in vivo. Both the
platinum (II) complex 2a and the
platinum (IV) complex 2b produced a significant number of cures over the dose range 10-40 mg/kg. The
platinum (II) complex 2a,
silaplatin, was very active in vivo against an
L1210 leukemia subline that was resistant to
cisplatin; 2a was also active, when given ip, against ic implanted L1210. The cyclobutanedicarboxylic
acid complex 3c was synthesized; this complex was active against both
cisplatin sensitive and resistant
L1210 leukemia but was less potent than the analogous dichloro compound 2a. The acyclic
platinum (II) and
platinum (IV) complexes 1a,b were synthesized and unexpectedly found to be inactive in vivo against
L1210 leukemia. More lipophilic
silaplatin analogues were prepared--Pt(II) complex 2c and Pt(IV) complex 2d have one additional methylene
carbon compared to 2a,b, whereas Pt(II) complex 2e and Pt(IV) complex 2f have two additional methylene carbons. Cyclization of the alkyl groups attached to the
silicon gave the spiro bicyclic Pt(II) complexes 10a and 11a and the Pt(IV) complexes 10b and 11b.