THE N3 POSITION OF N9-SUBSTITUTED ADENINE AS A METAL-ION BINDING-SITE- STRUCTURAL AND SOLUTION STUDIES WITH PD-II AND PT-II COMPLEXES OF N6',N6',N9-TRIMETHYLADENINE
C. Meiser et al., THE N3 POSITION OF N9-SUBSTITUTED ADENINE AS A METAL-ION BINDING-SITE- STRUCTURAL AND SOLUTION STUDIES WITH PD-II AND PT-II COMPLEXES OF N6',N6',N9-TRIMETHYLADENINE, Chemistry, 3(3), 1997, pp. 388-398
Steric blockage of the N1 and N7 sites of 9-methyladenine for metal co
mplexation is achieved by twofold methylation of the exocyclic amino g
roup. With 6',6',9-trimethyladenine (TrimeA), binding of M-II(dien) (M
= Pt, Pd) as well as of trans-[Pt(NH3)(2)Cl](+) therefore takes place
through N3. X-ray crystal structure determinations and NMR spectrosco
pic studies of three compounds are reported, and the effects of Pt-II
and Pd-II on the geometry and the acid-base properties of the TrimeA l
igand have been measured and compared with those of the free base. Tri
meA has a very pronounced self-stacking tendency in water (K = 85(M-1)
according to the isodesmic model of indefinite noncooperative self-as
sociation). Acidity constants derived from potentiometric pH titration
s, spectrophotometry, and NMR shift experiments display excellent agre
ement with each other. Twofold protonated TrimeA, that is H-2(TrimeA)(
2+), carries protons at the N7 and N1 sites; the acidity constants are
pK(H2(TrimeA))(H)=-0.75 and pK(H(TrimeA))(H)=4.15. These values compa
re well with those of other adenine residues. Protonation of [Pt(dien)
-(TrimeA-N-3)](2+) occurs at the N7 position, as shown by spectrophoto
metry and NMR spectroscopy. The acidity constant of the H+(N7) site in
this complex is low, that is pK(H[Pt(dien)(TrimeA)])(H)=0.3 (as deter
mined by spectrophotometry), but it is not as low as that for the same
site when a proton resides at N1 of unmetalated TrimeA. The pK(a) of
the doubly protonated complex, pK(H2[Pt(dien)(TrimeA)])(H), in which t
he second acidic proton is situated at N1, is about -1.2+/-0.3. These
findings indicate that upon metalation of N3, the sequence of adenine
protonation is reversed, While the N7 site still displays basic proper
ties, the N1 site has undergone a dramatic loss in basicity.