摘要:
IntroductionGuanine tetrads (or quartets) represent an unusual, yet important assembly of nucleic acid bases. They have been investigated by fiber X-ray crystallography about 40 years ago, even though they have been discovered much earlier.1Now they are an active area of research again because they are important building blocks of DNA and RNA tetraplex structures.2–4Tetraplex forming sequence motifs occur in telomeres at the ends of linear chromosomes. The proposed function of telomeres is maintenance of the structural integrity of the genome and insurance of complete replication at the chromosome termini. Similar sequence motifs do also occur in regulatory regions of oncogenes. Tetrads also play a role in supra-molecular chemistry, for example, guanosine analogs perform a self-assembly in columnar aggregates in the presence of cations.5Metal cations are indeed well known to be necessary for the formation of tetraplexes structures. They induce a stabilization following the order K+> Rb+> NH4+> Na+> Cs+> Li+for the monovalent ones, and Sr2+> Ba2+> Ca2+> Mg2+for the divalent ones.1Considering the ionic radii of these ions, it appears that a radius of approximately 1.2 Å is optimal.1This led to the idea that the stabilization is due to an optimal ratio of the cation size and the size of the cavity formed by the four guanines in the tetrad. The experimental studies on tetraplexes that followed have confirmed that the metals were very close to the axis, ions with large radii like K+are located int the cavity between two quartets, whereas ions with smaller radii like Na+may be located also in the central cavity of a single tetrad. For the cation selectivity of tetrads also solvation energies seem to have to be taken into account.6Guanine tetrads have also been investigated by quantum chemical studies. In order to assess the stability of such biomolecular complexes, Hartree–Fock,7,8and then DFT calculations showed that the bases can be linked in a Hoogsteen (Fig. 1b) pairing or by bifurcated H-bonds between N1-H, N2-H and O6(Fig. 1a).7,9,10However, the energy difference between the two conformations is very small and thus the relative energy depends on the quantum chemical method adopted. Calculations have also been undertaken in our group9,11or in others8for metallated tetrads, in the centre of the cavity or next to it. Such a bifurcated structure has not been found when cations are located in the central cavity formed by the tetrad.8From these facts it has been concluded that the metal ions change the hydrogen bond pattern in guanine tetrads. Meanwhile, quantum chemical calculations have been extended to sandwich type complexes formed by two guanine tetrads and a cation12and to several other tetrads reviewed inref. 3.Chemical structures and atomic numbering for the studied tetrads: bifurcated type a (a), Hoogsteen (b) and bifurcated type b (c).Tetrads have been investigated by different techniques,e.g.NMR spectroscopy, molecular dynamics and quantum chemistry, but the nature of the metal ion–ligand bonding seems controversial. On the basis of molecular dynamics calculations, Ross and Hardin viewed the interaction as covalent13while Gu and Lesczcynski imagined an electrostatic bonding analysing the electrostatic potential of quantum calculations.7Here we analyse the guanine tetrad metal ligand interaction by means of the Atoms In Molecules (AIM) method. The AIM theory has proved itself a valuable tool to conceptually define what is an atom, and above all what is a bond in a quantum calculation of a structure of a molecule.14The AIM theory has been applied to such systems as Van der Waals complexes or hydrogen bonded complexes15and more recently to characterize interactions between metal ions and ligands.16In the field of nucleic acids, the AIM formalism has been used for nucleosides,17nucleic base pairing18and guanine tetrads,19and the interaction of a magnesium ion with a base pair has also been studied.20The reader is addressed toref. 14for proper definition of bonding, bond paths, critical points on the basis of electronic density, its gradient and Laplacian, and toref. 17for a short summary of how it is employed in hydrogen bonding analysis. Using a similar approach, we perform an analysis of the interaction of the metal ion and the guanine ligand, and its influence on the tetrad structure and hydrogen bonding network, all of this on the basis of the analysis of the AIM topology of the electronic density, as a complementary study of the energetical one,9,11which only provides global, and not local information on molecular structure.
ISSN:1460-2733
DOI:10.1039/b210911e
出版商:RSC
年代:2002
数据来源: RSC