Hydrogen bonding in DNA base pairs: Reconciliation of theory and experiment

Up till now, there has been a significant disagreement between theory and e xperiment regarding hydrogen bond lengths in Watson-Crick base pairs. To in vestigate the possible sources of this discrepancy, we have studied numerou s model systems for adenine-thymine (AT) and guanine-cytosine (GC) base pai rs at various levels (i.e., BP86, PW91, and BLYP) of nonlocal density funct ional theory (DFT) in combination with different Slater-type orbital (STO) basis sets. Best agreement with available gas-phase experimental A-T and G- C bond enthalpies (-12.1 and -21.0 kcal/mol) is obtained at the BP86/TZ2P l evel, which (for 298 K) yields -11.8 and -23.8 kcal/mol. However, the compu ted hydrogen bond lengths show again the notorious discrepancy with experim ental values. The origin of this discrepancy is not the use of the plain nu cleic bases as models for nucleotides: the disagreement with experiment rem ains no matter if we use hydrogen, methyl, deoxyribose, or 5'-deoxyribose m onophosphate as the substituents at N9 and N1 of the purine and pyrimidine bases, respectively. Even the BP86/DZP geometry of the Watson-Crick-type di mer of deoxyadenylyl-3',5'-deoxyuridine including one Na+ ion (with 123 ato ms our largest model for sodium adenylyl-3',5'-uridine hexahydrate, the cry stal of which had been studied experimentally with the use of X-ray diffrac tion) still shows this disagreement with experiment. The source of the dive rgence turns out to be the molecular environment (water, sugar hydroxyl gro ups, counterions) of the base pairs in the crystals studied experimentally. This has been missing, so far, in all theoretical models. After we had inc orporated the major elements of this environment in our model systems, exce llent agreement between our BP86/TZ2P geometries and the X-ray crystal stru ctures was achieved.