The influence of metal alkali binding on the properties of hydrogen bonds in AantiGanti mispair
The O6 of guanine and N1 of adenine in the AantiGanti mispair are blocked by the hydrogen bonding. One can expect that N3 and N7 of guanine and adenine to be principal acceptors of cations. The G(3), G(7), A(3) and A(7) symbols are used to display these positions, respectively. The schematic representation of optimized structure of AantiGanti mispair in the presence of cations are presented in Figure 2. In agreement with previous studies [11. Sÿponer, J., Burda, J.V., Sabat, M., Leszczynski, J., Hobza, P. J. Phys. Chem. A,1998 , 102, 5951-5957.,34], calculations indicate that there is simultaneous coordination of the cation to both the N7 and O6 sites of guanine.
The binding energy has been evaluated using the following equation
∆E =Emispair ˗ ∑ Emon
Where Emispair and Emon are the energies of AantiGanti mispair and monomers in their optimized geometries (DNA bases, metal-adenine or metal-guanine), respectively (see Table 1). Unlike A(3) position, the cations binding to A(7), G(7) and G(3)-positions amplified the absolute values of binding energy ( ∆E ). For each ion type, the G(3) tautomer is the most stable among all. Contrary to A(7) position, the ∆Evalues in A(3), G(7) and G(3)-positions are in agreement with the charge/radius (q/rad) ratio of cations.
Also, the interaction (ΔEint) and deformation (ΔEdef) energies of the considered systems were calculated. The interaction energies were evaluated as the difference between the energy of the mispair and the sum of the energies of the separated monomers, by the same geometries as they have in the complex. The difference between the binding energy and the interaction energy is the deformation energy of the monomers (see Table 1). Unlike ΔEdef, the value of ΔEint is negative and makes a positive contribution to the ΔE. As evident from Table 1, the interaction energy is the most dominant contribution to the binding energy in all studied systems. The good relationship is found between ∆Eint and ∆E values with coefficient of determination R2= 0.9929 in studied systems.
The NH…O and NH…N hydrogen bonding (HB1 and HB2, respectively) intermolecular energies were calculated based on the Espinosa–Molins–Lecomte (EML) empirical criteria based on the obtained electron density distribution at the BCPs of the hydrogen bonds
EEML,HB = 0.5V(r)
Where V(r) is the value of a local potential energy at the BCPs (see Table 1). Contrary to G(7) and G(3)-positions, the absolute value of EEML,HB1 ( EEML,HB1) in A(7) and A(3)-positions upon interactions with alkali ions increases. An opposite behavior is found for EEML,HB2. The results indicate that unlike G(7) and G(3)-positions, increase in ion charge density in A(7) and A(3)-positions is accompanied by increasing in EEML,HB1and decreasing in the EEML,HB2values. For each ion, the EEML,HB1 and EEML,HB2 orders in AantiGanti mismatch are respectively as following:
A(7) > A(3) > G(3) > G(7)
G(7) > G(3) > A(7) > A(3)
The NH…O and NH…N hydrogen bond lengths (dHB1 and dHB2, respectively) in AantiGanti mismatch have been changed after interaction with cations. These distances are often treated as a rough measure of the strength of hydrogen bonds. As reported in Table 2, dHB1 in A(7) and A(3)-positions decreases, whereas dHB2 increases upon interactions with alkali ions. A reverse behavior is found for G(7) and G(3)-positions. The highest contraction in the HB1 and HB2 bond lengths correspond to Li+ cation in A(7) and G(7)- positions, respectively. Also, the highest expansion in the HB1 and HB2 bond lengths correspond to Li+ cation in G(7) and A(3)- positions, respectively. Contrary to A(3) and A(7) positions, the dHB1 values in G(7) and G(3)-positions are in agreement with the charge/radius (q/rad) ratio of cations. An opposite behavior is found for dHB2 values. Also, the results indicate that the shortest hydrogen bond length is related to highest absolute value of corresponding EEML,HB and vice versa.
For each individual NH…X (X=O, N) hydrogen bond, the combinations of dN–H and dX···H have been shown to be very useful for studying hydrogen bonding phenomenon [22. Golubev, N. S., Shenderovich, I. G., Smirnov, S. N., Denisov, G. S., Limbach, H. H. Chem Eur J , 1999 , 5, 492–497.].
q1 = 0.5 (dN–H ˗ dX···H)
q2 = dN–H + dX···H
Whereas the proton in NH…X (X=O, N) hydrogen bond is located on average closer to N, the q1 values is negative. On the other hand, q2 value goes through a minimum that leads to the strongly Nδ+···H···Xδ−hydrogen bond. The values of q1 and q2in studied systems are also gathered in Table 2. Contrary to A(7) and A(3)-positions, the absolute values of q1(q1) and q2 associated with HB1 increase in G(7) and G(3)-positions. This behavior is reversed for HB2. The results indicate that unlike A(7) and A(3)- positions, increase in ion charge density in G(7) and G(3)-positions is accompanied by increasing in q1and q2values corresponding HB1. A reverse order are found for q1and q2 values corresponding HB2.
For two type of considered hydrogen bond, there are good relationships between |q1|, q2 and corresponding bond length values. As evident from Figure 3, second order polynomial relationships are found between the absolute values of q1 and q2 and corresponding EEML for each hydrogen bond in considered systems.
Natural bond orbital (NBO) analysis stresses the role of intermolecular orbital interaction in the complex. In NBO theory, atomic charge assignments are based on natural population analysis, where each natural atomic charge is simply determined from the summed natural atomic orbitals populations on the atom [33. Reed, A. E., Weinstock, R. B., Weinhold, F. J. Chem. Phys . 1985 , 83, 735−746.]. The atomic charge on atoms involved in hydrogen bond formation in isolated adenine and guanine in the presence of cations have been calculated by NBO approach. One can see from Table 3 that the cation binding to N7 and N3 atoms of isolated adenine increases positive charge of H atom participating in HB1 and decreases negative charge of N atom participating in HB2. One can expected that the strength of HB1 increases due to interaction cations with adenine in these positions. This behavior is reversed for HB2. The interaction of cations with N3 atom of isolated guanine leads to increases positive charge of H atom participating in HB2 and decreases negative charge of O atom participating in HB1. Thus, the strength of HB1 and HB2 are expected to decrease and increase, respectively.
The negative and positive atomic charge on O and H atoms participating respectively in HB1 and HB2 increases due to interaction of cations with N7 atom of isolated guanine. One can expected that the strength of HB2 increases due to interaction cations with guanine in N7 site. Although, the negative atomic charge on O atom increased in this position, the strength of HB1 decreases. This can be explained by the fact that a second attractive side in guanine, i.e. not only nitrogen N7 but also oxygen O6.
For each acceptor NBO (j) and donor NBO (i), the stabilization energy E(2) associated with electron delocalization between donor and acceptor is estimated as:
\begin{equation} E^{2}=q_{i}\frac{\left(F_{i,j}\right)^{2}}{\varepsilon_{j}-\varepsilon_{i}}\nonumber \\ \end{equation}
Where qi is the orbital occupancy, εiand εj are diagonal elements, and Fi,jis the off-diagonal NBO Fock matrix element [45]. In Table 3, we analyze the main contributions to donor-acceptor second-order energies (E2). The most important donor–acceptor interactions connected to HB1 and HB2 are LpOσ *N–H and LpNσ *N–H, respectively. The results indicated that interaction of cations with N3 and N7 sites of adenine increase the E(2) values of HB1. A reverse behavior is found for N3 and N7 sites of guanine. The E(2) values of HB2amplified/diminished in the presence of cations in N3 and N7 positions of guanine /adenine. Contrary to G(7) and G(3)-positions, increase in ion charge density in A(7) and A(3)- positions is accompanied by increasing in E(2) values corresponding HB1. An opposite behavior are found for HB2. For HB1 and HB2 interactions, there is a good linear relationship between EEML values and corresponding E(2) values of these interaction (see Figure 4(a)). Also, the results indicate that second order polynomial correlation exists between the E(2) values and corresponding hydrogen bond lengths with coefficient of determination R2=0.9985 and in R2=0.9980 respectively for HB1 and HB2 in studied systems.
The QTAIM is useful to analyze various intra and intermolecular interactions. The results indicate that the bond critical points of the hydrogen bonds was found. The electron density at the BCP of the hydrogen bond may be treated as a measure of the hydrogen bond strength [44. Galvez, O., Gomez, P. C., Pacio, L. F. J. Chem. Phys . 2003 , 118, 4878‒4895.,55. Domagala, M., Grabowski, S. J. J. Phys. Chem. A. 2005 , 109, 5683‒5688.]. Rozas et al. have introduced a classification of hydrogen bonds according to their strength [66. Rozas, I., Alkorta, I., Elguero, J. J. Am. Chem. Soc . 2000 , 122, 11154‒11161. Figure1. Electrostatic potentials mapped on the molecular surfaces of isolated (a) guanine, (b) adenine bases with VMD software. Figure 2. The Schematic representation of optimized structure of AantiGanti mispair in the presence of cations (M= Li+, Na+ and K+ ) in (a) N3 (b) N7 sites of adenine and (c) N3 (d) N7 sites of guanine, respectively. Figure 3. Relationships between EEML values and (a) q1 and (b) q2 for each hydrogen bond in AantiGanti systems involving cations. The (●) and (▲) symbols correspond to HB1 and HB2, respectively. Figure 4. Relationships between EEML and corresponding (a) E(2) and (b) ρ(r) values for each hydrogen bond in AantiGanti systems involving cations. The (●) and (▲) symbols correspond to HB1 and HB2, respectively. Figure 5. The Schematic representation of optimized structure of AsynGanti mispair in the presence of cations (M= Li+, Na+ and K+ ) in (a) N1 (b) N3 sites of adenine and (c) N3 (d) N7 sites of guanine, respectively. Figure 6. Relationships between EEML values and (a) q1 and (b) q2 for each hydrogen bond in AsynGanti systems involving cations. The (●) and (▲) symbols correspond to HB1 and HB2, respectively. Figure 7. Relationships between EEML and corresponding (a) E(2) and (b) ρ(r) values for each hydrogen bond in AsynGanti systems involving cations. The (●) and (▲) symbols correspond to HB1 and HB2, respectively]. Weak H-bonds show both ∇2ρ(r) and H(r) values positive; for medium H-bonds ∇2ρ(r)> 0 and H(r)< 0 and also for strong H-bonds the ∇2ρ(r) as well as H(r) are negative. The results of AIM analysis are gathered in Table 4. Unlike G(3) and G(7)-positions, the ρ(r) values at the BCP of the HB1 (ρHB1) in the presence of cations in N7 and N3-positions of adenine increase. The ρ(r) values at the BCP of HB2HB2) amplified/diminished in the presence of cations in N3 and N7 positions of guanine /adenine. Contrary to G(7) and G(3)- positions, the ρHB1 values in A(3) and A(7) positions are in agreement with the charge/radius (q/rad) ratio of cations. An opposite behavior is found for ρHB2 values. The nature of hydrogen bonds in considered complexes is dependent on position of cations. In the presence of cations in N3 and N7 sites of adenine, HB1 has medium strength while HB2 of weak strength is observed. Here, AantiGanti mispair involving cations in N3 and N7 positions of guanine are characterized by the positive values of ∇2ρ(r) and H(r) in the BCP of the HB1 showing that this interaction may be classified as weak bonds. Although ∇2ρ(r) at the BCP of the HB2 in systems involving cations in N3 and N7 positions of guanine is positive, H(r) is negative, indicating that HB2 has medium strength. The results indicate that there are good linear relationships between E(2) values and corresponding ρ(r) at the BCP of hydrogen bonds of considered systems. The linear coefficients of determination between ρHB1 (and ρHB2) and E(2) values are equal to 0.9993 (and 0.9968). The ρ(r) values and corresponding distance of interactions also show good reverse relationships. Figure 4(b) shows that there are good linear relationships between ρ(r) values and corresponding EEML in studied systems. One can see that the maximum value of the ρ(r) is related to highest absolute value of corresponding EEML for both types of hydrogen bond and vice versa.