Substitution reactions of the complexes [Pt(terpy)(H(2)O)](2+), [Pt(terpy)(
cyst-S)](2+) and [Pt(terpy)(guo-N(7))](2+), where terpy = 2,2':6',2"-terpyridine,
cyst =
L-cysteine and guo =
guanosine, with some biologically relevant
ligands such as
inosine (INO), inosine-5'-monophosphate (5'-IMP), guanosine-5'-monophosphate (5'-GMP),
l-cysteine,
glutathione,
thiourea,
thiosulfate and
diethyldithiocarbamate (DEDTC), were studied in aqueous 0.10 M NaClO(4) at pH 2.5 and 6.0 using variable-temperature and -pressure stopped-flow spectrophotometry. The reactions of [Pt(terpy)(H(2)O)](2+) with INO, 5'-IMP and
5'-GMP showed that these
ligands are very good nucleophiles. The second order rate constants varied between 4 x 10(2) and 6 x 10(2) M(-1) s(-1) at 25 degree C. The [Pt(terpy)(
cyst-
S)](2+) complex is unreactive towards
nitrogen donor nucleophiles, and
cysteine cannot be replaced by N(7) from INO, 5'-IMP and
5'-GMP. However,
sulfur donor nucleophiles such as
thiourea,
thiosulfate and
diethyldithiocarbamate could displace the Pt-
cysteine bond.
Diethyldithiocarbamate is the best nucleophile and the order of reactivity is:
thiourea <
thiosulfate < DEDTC with rate constants of 0.936 +/- 0.002, 5.99 +/- 0.02 and 8.88 +/- 0.07 M(-1) s(-1) at 25 degree C, respectively. The reactions of [Pt(terpy)(guo-N(7))](2+) with
sulfur donor
ligands showed that these nucleophiles could substitute
guanosine from the Pt(ii) complex, of which
diethyldithiocarbamate and
thiosulfate are the strongest nucleophiles. The tripeptide
glutathione is also a very efficient nucleophile. Activation parameters (Delta H(++), Delta S(++) and Delta V(++)) were determined for all reactions. The crystal structures of [Pt(terpy)(
cyst-S)](ClO(4))(2).0.5H(2)O and [Pt(terpy)(guo-N(7))](ClO(4))(2).0.5guo.1.5H(2)O were determined by X-ray diffraction. Crystals of [Pt(terpy)(
cyst-S)](ClO(4))(2).0.5H(2)O are orthorhombic with the space group P2(1)2(1)2(1), whereas [Pt(terpy)(guo-N(7))](ClO(4))(2).0.5guo.1.5H(2)O crystallizes in the orthorhombic space group P2(1)2(1)2. A typical feature of terpyridine complexes can be found in both molecular structures: the Pt-N (central) bond distance, 1.982(7) and 1.92(2) A, respectively, is shorter than the other two Pt-N distances, being 2.043(7) and 2.034(7) A in [Pt(terpy)(
cyst-S)](ClO(4))(2).0.5H(2)O and 2.03(2) and 2.04(2) A in [Pt(terpy)(guo-N(7))](ClO(4))(2).0.5guo.1.5H(2)O, respectively. In both crystal structures two symmetrically independent
cations representing different conformers are present in the asymmetric unit. The results are analysed in reference to the antitumour activity of Pt(II) complexes, and the importance of the rescue agents are discussed.