The influence of a sugar-phosphate backbone on the cisplatin-bridged BpB′ models of DNA purine bases. Quantum chemical calculations of Pt(ii) bonding characteristics

The optimised structures of cis-[Pt(NH3)2-1,2-d{BpB′}]2+ (B and B′ are guanine and adenine bases in all four combinations) were determined at the B3LYP/6-31G(d) level of calculations. The optimised parameters of the [Pt(NH3)2-{GpG}]2+ complex are in very good agreement with the experimental data. The RMS of the predicted molecular parameters from the crystal structure is approximately 1.0 Å, even less than the difference between several experimental structures which are available in the NDB database. For the obtained reference geometries, an estimation of the bond dissociation energies (BDE), stabilisation energies ΔEstab, and ΔEstex together with the natural bond orbital population analysis (NBO) and MO analyses were performed using the MP2/6-31+G(d) method. The Pt–N7 bond is always stronger in the case of 3′-end base than for the 5′-end one. The highest abundance of a Pt-adduct to GpG, known from experiment, was confirmed by the predicted highest stabilisation of this complex. Also experimentally revealed, 20% of Pt{ApG} bridges simultaneously with practically no occurrence of Pt{ApA}, and this is in qualitative correspondence with the computed stabilisation. The explanation of the negligible occurrence of Pt{GpA} could originate in the kinetic and/or sterical conditions in the DNA chain since the monofunctional platinated complex contains exclusively guanine. Then if adenine is present above guanine (at the 5′-end), the N7 position of adenine is in close proximity of the second leaving group of cisplatin which increases the probability for the formation of Pt-{ApG}.