Supramolecular Switches Based on the Guanine–Cytosine (GC) Watson–Crick Pair: Effect of Neutral and Ionic Substituents

Abstract

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(-), NH(2), NH(3) (+) (N series), O(-), OH, or OH(2) (+) (O 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.

On the nature of halogen bond – The Kohn–Sham molecular orbital approach

“…The main force stabilizing H-bonding is DE oi term. This clearly shows the covalent nature of H-bond, which has already been reported on the basis of high quality theoretical [38,39] and experimental [40] investigations. What is particularly important, similarly as in halogen bonding also in H-bonding the stronger interaction appears for iodine acting as proton acceptor whereas the weakest interaction is observed for chlorine derivatives.…”

The Nature of Hydrogen Bonds: A Delineation of the Role of Different Energy Components on Hydrogen Bond Strengths and Lengths

“…The electrostatic interaction ( Figure 1a) will generally become strongerw hen the partial charges on the frontier atom are enhanced, which can be achieved by modifying the moleculars tructure. [6,[11][12][13][14] The electrostatic interaction DV elstat between two hydrogenbonded monomers Aa nd Bcan be written as where Z a and R a are the nuclear charge and position of atom a,r espectively,a nd 1(r)i st he molecule's electronic density. The first term is the repulsive Coulombic interaction between the nuclei of monomer Aw ith those in monomer B, the second and third terms are the attractive Coulombic interactions between the electrons of monomer Aw ith the nuclei in monomer Ba nd vice versa,a nd the last term is the repulsive Coulombic interaction between the electrons in monomer A with those in monomer B. However,a si ti sc omputationally demanding to obtain an accurate electronic density,p articularly for large molecular systems, the electrostatic interaction has been approximated by simpler models.…”

“…These substituent effects were for example studied by Fonseca Guerrae tal. [11][12][13] by introducing substituents on remote positions in the DNA base pairs guanine-cytosine (GC) and adenine-thymine (AT) and by Gilli and Gilli [37] for enaminones derivatives. The covalentn ature of HBs has been highlighted in many studies.…”

Watson-crick base pairs with thiocarbonyl groups: How sulfur changes the hydrogen bonds in DNA

“…[9][10][11][12][13][14][15][16][17][18][19] In our previous work, [20][21][22][23][24][25] we showed that the generalized gradient approximation (GGA) of density functional theory (DFT) is an efficient alternative to conventional ab initio theory for accurately describing the hydrogen bonds involved in Watson-Crick base pairs (AT and GC, see Scheme 1) and in the weakly bound water dimer. [21] Our bond analyses in the frame of Kohn-Sham DFT [26] revealed that the contribution of occupied-virtual orbital interactions to the Watson-Crick hydrogen bonds is of the same order of magnitude as electrostatic interactions.…”

“…[21] Our bond analyses in the frame of Kohn-Sham DFT [26] revealed that the contribution of occupied-virtual orbital interactions to the Watson-Crick hydrogen bonds is of the same order of magnitude as electrostatic interactions. [20][21][22][23][24][25] The orbital interaction component mostly originates from donor-acceptor interactions of lone pairs on nitrogen and oxygen atoms of one DNA base with empty N-H s* orbitals of the other base. [20,21,23] Very recently, we found that, at variance with widespread believe, [27][28][29][30][31] such an orbital interaction component is prominent even in rather weakly bound base pairs, such as those of adenine (A) with 2,4-difluorotoluene (F), a mimic of thymine (T), and of fluorine-substituted mimics of G and C, respectively.…”