Substitution of inosine and guanosine 5′-monophosphate for chloride, and water on PdII(polyaminopolycarboxylate) complexes: mechanistic controls in forming PdII(pac)L or PdII(pac)L2 products

The substitution of one inosine (Ino) with [PdII(pac)(D2O)] complexes (pac=polyaminopolycarboxylate with pac=mida2−) and [Pd2 II(pac)(D2O)2] (pac=hdta4− and egta4− produce products in which the entering Ino ligand resides trans to the iminodiacetate N donor and the two glycinato arms of the iminodiacetate donor have a ‘one on, and one off’ arrangement. Reactions were carried out in the pD range of 5.0–6.0 in order to assure that glycinato carboxylates would be coordinated in the starting [Pd(pac)(D2O)] complex and in a range such that the final coordination of inosine is favored at the N-7 donor site. The structure of the product was deduced from 1H and 13C NMR studies. These [Pd(pac)L] products are consistent with a common trigonal bipyramidal intermediate with the entering Ino group displacing an in-plane glycinato group. Substitution of one Ino on [PdII(mida)Cl]− results in both glycinato donors being made pendant. A different, more square–pyramidal intermediate leads to this product whereas a TBP geometry will not. The tendency toward formation of stable bis [PdII(pac)L2] products increases in the order of the pac ligand of 1/2 egta4−>1/2 hdta4−>mida2−, indicating that strain at the central iminodiacetates’ nitrogen donor favors displacement of the second glycinato chelate, but that having binuclear PdII centers too close disfavors forming bis-derivatized PdII headgroups. Rather, the longer eight methylene equivalent spacer in [Pd2(egta)(H2O)2] compared to six methylenes in [Pd2(hdta)(H2O)2] allows for bis addition at both PdII centers to proceed to completion. If the entering ligand is the anionically charged 5′-GMP nucleotide instead of the neutrally charged Ino, addition stops at the ‘one on, one off’ 1:1 complex per PdII center with [Pd2(egta)(H2O)2], just as Ino addition to the anionically charged [Pd(mida)Cl]− stops at the first addition step. Two types of PdII derivatized isomer are detected for the [Pd2(Ino)4(hdta)] complex, e.g. with Ino groups either trans or cis to each other. 31P NMR studies show that association of the phosphate ester unit of 5′-GMP or of H2PO4 − make only transitory interactions with the PdII center such that a rearrangement that is observed on a slow time scale of >24 h for the decay of an unstable isomer of [Pd2(5′-GMP)2(egta)]2 − must be due to an N-1 to N-7 rearrangement, rather than a phosphate ester coordination to N-4 migration. Likewise, unstable species are found by 1H NMR for Ino substitutions on [Pd(mida)Cl]− and [Pd2(hdta)(D2O)2]. The processes that alter the initial distribution of species are attributed to N-1 to N-7 isomerisms. The major substitution product for Ino or 5′-GMP, in all cases of Pd(pac) substitutions, is the N-7 coordinated purine nucleoside or nucleotide, as shown by 1H NMR parameters of the several species. In this manner, the behavior of PdII(pac) coordination of purine nucleobases parallels the behavior of PdII–dipeptide and tripeptide complexes in forming ternary complexes with DNA nucleobases. Both PdII(pac) and PdII(peptide) complexes have neutral or anionic reaction centers. In contrast, the cationic PdII(dien) purine complexes favor N-1 coordination much more strongly, and are therefore poorer models of ternary protein–metal ion–DNA nucleobase interactions of importance in transcription processes and cytotoxic DNA–protein crosslinks.