Calorimetric and 195Pt NMR Studies on Aromatic Ring Stacking between Nucleotides and Platinum DNA Intercalators

Abstract

Calorimetric and spectroscopic investigations have been carried out on the stacking interactions between nucleosides or nucleotides (NMP) and platinum DNA intercalators and other planar platinum(II) complexes with heteroaromatic ligands (L). Pt(L)(diamine) (L = 1,10-phenathroline (phen), its methyl and nitro derivatives, 2,2′-bipyridine; diamine = ethylenediamine (en), L-2,3-diaminopropionate) reacts with NMP (=adenosine 5′-monophosphate (AMP), guanosine 5′-monophosphate (GMP), inosine 5′-monophosphate (IMP), cytidine 5′ -monophosphate (CMP); nicotinamide adenine dinucleotide (NAD), adenosine, cytidine) to give the Pt(L)(diamine)–(NMP)n adducts (n = 1, 2) with log K1 = 1.63—3.00 and log K2 = 1.47—2.51 at 25 °C at ionic strength = 0.1 mol dm−3 (NaCl). The 1 : 1 adduct formation mainly depends on the enthalpy change ΔH1° = −6.5 — −26.2 kJ mol−1, and the entropy change (ΔS1° = −38—20 J mol−1 K−1) makes a negative or small contribution. 1H NMR upfield shifts observed for the Pt(phen)(en)–NMP systems have substantiated the presence of stacked adducts in dilute aqueous solution, whereas diquat, a dicationic organic molecule, did not cause appreciable shifts, and hence the adduct formation was negligible. NAD was found to interact with Pt(phen)(en) through the adenine moiety. 195Pt NMR signals of Pt(phen)(en) in water suffered downfield shifts upon addition of NMP, the Δδ1 values being in the order NAD ≥ AMP ≈ GMP > IMP. This indicates that stacking causes an electron density decrease of the Pt(II) center. Linear relationships have been detected between the ΣΔHn° values and the absorption coefficients εn of the difference spectra in the charge transfer region and between ΣΔHn° and 195Pt NMR shift differences Δδn. These observations serve as evidence for the electronic effects of stacking interactions on the stacked rings and the central Pt(II) ion.

Tuning the Aggregation of N^N^C Pt(II) Complexes by Varying the Aliphatic Side Chain and Auxiliary Halide Ligand: 1H and 195Pt NMR Investigation

“…The deshielding may be a consequence of a small charge delocalization from the Pt atom due to the action of the above‐located large dipole of the Pt‐halogen moiety of the partner molecule. Similar deshielding of 195 Pt nucleus was also reported before for stacking of Pt‐containing heterocyclic compounds with nucleotides and also explained by charge delocalization in Pt atom , . Noteworthy, the solution study of the self‐association of related Pt complex of phenanthroline also resulted in antiparallel structure, qualitatively similar to that obtained in the present work.…”

“…0.3 ··· 0.4 ppm, are consistent with the ring‐current effect originating from diamagnetic shielding induced by delocalized aromatic π‐electrons circulating around the aromatic moieties of the molecules, located above each other inside a dimer . This configuration is possible only for the face‐to‐face orientation of the molecules in aggregates , …”

π–π Stacking assisted binding of aromatic amino acids by copper(ii)–aromatic diimine complexes. Effects of ring substituents on ternary complex stability

“…13 The adduct formation between planar Pt(II) complexes, Pt(DA)(L') (L' = ethylenediamine or amino acids), and mononucleotides was revealed to be enthalpically driven mainly through stacking interactions by the relevant thermodynamic parameters 14 and decrease the electron density of the Pt(II) center as seen from and the downfield shift of the 195 Pt NMR signal. 15 The adduct stability sequence due to DA,3,4,7,10-phenanthroline > 1,10-phenanthroline ≈ 5-nitro-1,10-phenanthroline, reflected the effects of the DA substituents on stacking. In this connection, Kohzuma et al reported that the Cu center of the plastocyanin from a fern Dryopteris crassirhzoma has a phenylalanyl residue stacked with a coordinated histidine (His90) and, probably as a result of this, exhibits a higher redox potential than that of higher plant plastocyanins.…”

A spectroscopic investigation of the self-association and DNA binding properties of a series of ternary ruthenium(II) complexes

“…The 1 H NMR spectra were recorded from freshly prepared solutions of the complexes at concentrations of 1, 3,5,10,15,20,25,35,45 and 55 mM in D 2 O containing the internal reference and NaCl (100 mM).…”

“…The planar aromatic drugs proflavine and acridine orange, which are well known to be strong DNA intercalators, [6] self-associate in aqueous solutions via stacking interactions [7]. Stacking interactions in solution also occurs for inorganic complexes possessing a planar aromatic 0162 [15] and other related Pt(II) complexes [16]. The ternary Ru(II) complex [Ru(phen) 3 ] 2+ selfassociates by a stacking interaction in aqueous solution, [17] but the mode by which this complex binds to DNA (either intercalative or electrostatic groove binding) is the subject of some debate [18][19][20][21][22].…”