Substitution of inosine and guanosine 5 '-monophosphate for chloride, and water on Pd-II(polyaminopolycarboxylate) complexes: mechanistic controls informing Pd-II(pac)L or Pd-II(pac)L-2 products

The substitution of one inosine (Ino) with [Pd-II(pac)(D2O)] complexes (pac = polyaminopolycarboxylate with pac = mida(2-)) and [Pd-2(II)(pac)(D2O)(2) ] (pac=hdta(4-) and egta(4-) produce products in which the entering Ino lig and resides trans to the iminodiacetate N donor and the two glycinato arms of the iminodiacetate donor have a 'one on, and one off arrangement. Reacti ons were carried out in the pD range of 5.0-6.0 in order to assure that gly cinato carboxylates would be coordinated in the starting [Pd(pac)(D2O)] com plex 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 H-1 an d C-13 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 tno on [Pd-II(mida)Cl](-) re sults in both glycinato donors being made pendant. A different, more square -pyramidal intermediate leads to this product whereas a TBP geometry will n ot. The tendency toward formation of stable bis [Pd-II(pac)L-2] products in creases in the order of the pac ligand of 1/2 egta(4-) > 1/2 hdta(4-) > mid a(2-), indicating that strain at the central iminodiacetates' nitrogen dono r favors displacement of the second glycinato chelate, but that having binu clear Pd-II centers too close disfavors forming bis-derivatized Pd-II headg roups. Rather, the longer eight methylene equivalent spacer in [Pd-2(egta)( H2O)(2)] compared to six methylenes in [Pd-2(hdta)(H2O)(2)] allows for bis addition at both Pd-II centers to proceed to completion. If the entering li gand 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 Pd-II c enter with [Pd-2(egta)(H2O)(2)], just as Ino addition to the anionically ch arged [Pd(mida)Cl](-) stops at the first addition step. Two types of Pd-II derivatized isomer are detected for the [Pd-2(Ino)(4)(hdta)] complex, e.g. with Ino groups either trans or cis to each other. P-31 NMR studies show th at association of the phosphate ester unit of 5'-GMP or of H2PO4; make only transitory interactions with the Pd-II center such that a rearrangement th at is observed on a slow time scale of > 24 h for the decay of an unstable isomer of [Pd-2(5'-GMP)(2)(egta)](2)(-) must be due to an N-1 to N-7 rearra ngement, rather than a phosphate ester coordination to N-4 migration. Likew ise, unstable species are found by H-1 NMR for Ino substitutions on [Pd(mid a)Cl](-) and [Pd-2(hdta)(D2O)(2)]. The processes that alter the initial dis tribution of species are attributed to N-1 to N-7 isomerisms. The major sub stitution 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 H-1 NM R parameters of the several species. In this manner, the behavior of Pd-II( pac) coordination of purine nucleobases parallels the behavior of Pd-II-dip eptide and tripeptide complexes in forming ternary complexes with DNA nucle obases. Both Pd-II(pac) and Pd-II(peptide) complexes have neutral or anioni c reaction centers. In contrast, the cationic Pd-II(dien) purine complexes favor N-1 coordinati on much more strongly, and are therefore poorer models of ternary protein-m etal ion-DNA nucleobase interactions of importance in transcription process es and cytotoxic DNA-protein crosslinks. (C) 2000 Elsevier Science B.V. All rights reserved.