Supramolecular switches based on the guanine-cytosine (GC) Watson-Crick pair: Effect of neutral and ionic substituents

We have theoretically analyzed Watson-Crick guanine-cytosine (GC) base pairs in which purine-C8 and/or pyrimidine-C6 positions carry a substituent X = NH-, NH2, NH3+ (N series), O-, OH, or OH,1 (0 series), using the generalized gradient approximation (GGA) of density functional theory at the BP86/TZ2P level. The purpose is to study the effects on structure and hydrogen-bond strength if X = H is substituted by an anionic, neutral, or cationic substituent. We found that replacing X = H by a neutral substituent has relatively small effects. Introducing a charged substituent, on the other hand, led to substantial and characteristic changes in hydrogen-bond lengths, strengths, and hydrogen-bonding mechanism. In general, introducing an anionic substituent reduces the hydrogen-bond-donating and increases the hydrogen-bond-accepting capabilities of a DNA base, and vice versa for a cationic substituent. Thus, along both the N and O series of substituents, the geometric shape and bond strength of our DNA base pair can be chemically switched between three states, thus yielding a chemically controlled supramolecular switch. Interestingly, the orbital-interaction component in some of these hydrogen bonds was found to contribute to more than 49% of the attractive interactions and is thus virtually equal in magnitude to the electrostatic component, which provides the other (somewhat less than) 51% of the attraction.