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DFT Studies on the Copper(II) Complexes of DNA Bases
DFT Studies on the Copper(II) Complexes of DNA Bases
Journal of the Korean Chemical Society. 2007. Feb, 51(1): 101-105
Copyright © 2007, The Korean Chemical Society
  • Received : October 28, 2006
  • Published : February 20, 2007
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Abstract
Keywords
RESULTS AND DISCUSSION
In . 1 , the most significant geometrical parameters of stable Cu 2+ -DNA bases complexes obtained by B3LYP/6-31G(d,p) computations are reported. The copper(II) cation association energies of DNA bases are summarized in 1 .
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B3LYP-optimized structures for Cu2+ complexes of AC) adenine, TC) thymine, GC) guanine, and CC) cytosine. Selected distances are in Å.
All optimized structures in . 1 have C s symmetry except C 1 of the CC2.
On the other hand, the cupric cation association energies of DNA bases are calculated to be about 200~260kcal/mol as shown in 1 . These energies are larger than that of Cu + complexes (90~140 kcal/mol) 14 and are similar to that of Zn 2+ complexes (180~250 kcal/mol). 13 This means that the association energy relates to charge of the metal ion.
As shown in . 1 , the five distinct complexes of Cu 2+ with adenine have been found. The structure of AC5 in the five complexes was not located in Cu + complex. 14 The cupric cation association energies of these complexes are about 230 kcal/mol except N 7 complex of about 225 kcal/mol as shown in 1 .
Association of adenine with Cu 2+ is accompanied by structural changes within the pyrimidine ring. When Cu 2+ binds at the N 1 and N 6 atoms(AC1 in . 1 ), the N 1 -C 2 distance increases by 0.023Å compared to the parent base, whereas the C 5 -C 6 bond length of 1.411Å is reduced to 1.373Å in the complex. The notable change in bond lengths is an increase of 0.103Å in the C 6 -N 6 distance. The C 5 C 6 N 6 angle also changes considerably, increasing by 8.7°. The two dihedral angles (∠N 1 C 6 N 6 H) of -10.0 and -170.1° by amino hydrogens in adenine change to 119.7 and -119.7° in N 1 -N 6 complex, respectively. This is due to the repulsion between the Cu 2+ and amino hydrogen on the N 1 side of the C 6 -N 6 bond. That is, the amino hydrogens rotate to reduce this repulsion. The N 1 -Cu 2+ and N 6 -Cu 2+ distances of this complex are calculated to be 1.893 and 1.969Å, respectively. When Cu 2+ binds at N 3 (AC2 in . 1 ), the N 1 -C 2 bond length decreases by 0.051Å and the C 2 -N 3 distance increases by 0.077Å. The N 3 -Cu 2+ distance is 1.801Å. All other bond distance and bond angle changes are small. For the bridging complex in which Cu 2+ forms a five-membered ring (AC3 in . 1 ), the N 7 -Cu 2+ distance is 1.897Å and the N 6 -Cu 2+ is 2.025Å. The C 5 C 6 N 6 angle changes considerably, decreasing by 8.2°. This large change is associated with bridging nature of the complex caused by interaction of Cu 2+ with the N 6 and N 7 atoms. The N 1 -Cu 2+ distance in the N 1 complex(AC4 in . 1 ) is calculated to be 1.815Å and N 7 -Cu 2+ distance in N 7 complex(AC5 in . 1 ) is calculated to be 1.800Å.
B3LYP/6-31G(d,p) absolute energies (E in au) of the copper (II) complexes and cupric cation association energies (ΔEcain kcal/mol) of DNA bases
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aΔEc = ΔE + ΔZPE + BSSE
The two association sites for Cu 2+ complex with thymine have been found, one at each carbonyl group, as shown in . 1 . These features are similar to Zn 2+ complex. 14 The association energies of these complexes are calculated to be -207.74 and -203.10 kcal/mol in the O 2 and O 4 complex, respectively. The O-Cu 2+ distances are 1.771 and 1.792Å. In this complex, the notable change is an increase in the internal angle of the ring at carbon of the carbonyl binding site, and increase in the carbonyl C=O bond lengths. The N 1 C 2 N 3 angle in the O 2 complex increases by 3.3° and the N 3 C 4 C 5 angle in the O 4 complex increases by 6.2°. The C=O bond distances increase upon complexation by 0.033 and 0.085Å in the O 2 and O 4 complex, respectively.
The three distinct complexes of Cu 2+ with guanine have been found as shown in . 1 . The most stable guanine complex is the bridging complex in which Cu 2+ forms a five-membered ring, interacting with the O 6 and N 7 atoms. The cupric cation association energy of this complexes is -262.54 kcal/mol as shown in 1 . The five-membered ring formation (GC2 in . 1 ) is about 40 kcal/mol more stable than the four-membered ring formation (GC1 in the . 1 ). This result shows that the five-membered ring formation is favored with respect to formation of four-membered ring because of the minor annular strain. This O 6 -N 7 five-membered ring complex of Cu 2+ with guanine is the strongest of the Cu 2+ complexes with the DNA bases as seen in 1 . This tendency is similar to that obtained for the Zn 2+ complex. 14 In five-membered ring complex, the C 5 C 6 O 6 angle decreases notably by 13.3° in comparison with parent base. This large change is also associated with the bridging nature of complex. The O 6 -Cu 2+ and N 7 -Cu 2+ distances of this complex are calculated to be 1.863 and 1.915A, respectively. On the other hand, the two N-Cu 2+ distances in four-membered ring complex are found to be 1.937 and 2.073A. And N-Cu 2+ distance in N 3 complex (GC3 in . 1 ) is calculated to be 1.814A.
The two bridged formations have been found in the cytosine complex in which Cu 2+ forms fourmembered ring with O 2 -N 3 and N 3 -N 4 as shown in . 1 . The O 2 -N 3 bridging complex is more stable than N 3 -N 4 complex. This result means that the carbonyl oxygen is preferred over the amino nitrogen. In the O 2 -N 3 complex, notable changes occur in bond distances and angles from N 1 to C 4 . The N 1 -C 2 distance decreases by 0.095Å and N 1 C 2 O 2 angle increases by 6.8° with complexation. These results lead to enhancement of the simultaneous interaction of Cu 2+ with O 2 and N 3 . Similarly, the N 3 C 4 N 4 angle in the N 3 -N 4 complex is reduced upon complexation to about 11.3°. In the O 2 -N 3 complex, the O 2 -Cu 2+ and N 3 -Cu 2+ distances are 1.853 and 1.942Å, respectively. In this complex, the O-Cu 2+ distance is longer than the corresponding ones in the thymine complexes. The association energy of this complex is -245.71 kcal/mol. On the other hand, the N-Cu 2+ distances in N 3 -N 4 complex are calculated to be 1.865 and 1.997Å.
In conclusion, there are five distinguishable Cu 2+ complexes with adenine, two bridging complexes and the other three open structures at N 1 , N 3 and N 7 , respectively. There are two Cu 2+ complexes with thymine, one at each carbonyl group. The three distinct complexes of Cu 2+ with guanine are found, two bridging guanine-Cu 2+ complexes and an open structure at N 3 . For the cytosine-Cu 2+ complex, there are two bridging complexes, one at the O 2 and N 3 atoms, and the other at the N 3 and N 4 atoms.
In this study, structures and energetic aspects of the complexes of copper(II) with DNA nucleobases were investigated at B3LYP/6-31G(d,p) density functional level. The association energy values suggest that the most stable of the Cu 2+ complexes with DNA bases are the bridging complexes with guanine and cytosine at the O and N atoms. This means that the coordination sites are the O and N atoms as the most suitable to receive the metal cations. The most favorable association energy values for each base suggest that the DNA bases reactivity order with Cu 2+ is guanine > cytosine > adenine > thymine. This tendency of Cu 2+ metal affinities is in agreement with the experimental results from kinetic method for the alkali metals (Li + , Na + , K + ). 8
The results obtained in this study are the first theoretical consideration that concerned the Cu 2+ interactions with DNA bases. These gas-phase results can be used with caution as a guideline for both the binding sites and association energies for the condensed phase.
Acknowledgements
This research was supported by the Catholic University of Daegu research grants in 2006.
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