Resolution Of The Chiral Polypyridyl Metal Complexes And Research On Enantioselective Interaction Of The Complexes With DNA

In recent years, the interaction between small molecular transition metal complexes and DNA has been an active subject at international bioinorganic chemistry field. Octahedral polypyridyl transition metal complexes have been used extensively as DNA structural probes, molecular light-switch, electron transfer for DNA, DNA footprinting reagents and DNA cleavaging reagents and so on. Compare with other metal complexes, polypyridyl ruthenium complexes have A- and A- isomers, and they all have special photophysical and photochemical properties. These properties make them suitable for recognizing DNA and interaction with DNA.In the beginning of 1980's, J.K.Barton discovered some chiral metal complexes can provide unique molecular probes for DNA when she studied metal ions interaction with DNA. As a result, the chiral metal complexes provide sensitive probes both for B- and Z- handed DNA. Furthermore, binding mode of some complexes to DNA were studied, they found that there exists enantioselectivity for complexes binding to CT-DNA. The DNA-binding of the A-isomer is stronger than that of the A-isomer, whereas that of the A-isomer is swifter. Under UV light irradiation, these chiral complexes can induces single-strand or double-strand cleavage of DNA, which is very helpful for the understanding of the mechanisms of DNA cleavage and the design and exploitation of new clinic anti-cancer drugs.In this paper, three chiral metal complexes were synthesized and resolution systematically by referring to literature methods. The action modes of these complexes with DNA were studied. We have made some scientific researched as follow:1. We have synthesized a series of ligands: HPIP, DMNP and BOPIP. (HPIP= (2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline, DMNP=4-(1H-imidazo[4,5-f] [1,10]phenanthrolin-2-yl)-N,N-dimethylbenzenamine, BOPIP=2-(4- but- oxyphenyl)-1H -imidazo[4,5-f][1,10] phenanthroline),and their structures are deduced with elemental analysis, infrared spectra, nuclear magnetic resonance spectra, Ultra-visible absorption spectra.2. The chiral polypyridyl metal complexes of [Ru(bpy)2HPIP](C104)2, [Ru(bpy)2DMNP](C104)2 and [Ru(bpy)2BOPIP](ClO4)2, have been designed, synthesized and ascertained their rough structures with elemental analysis, infrared spectra, nuclear magnetic resonance spectra, Ultra-visible absorption spectra and molar electrolytic conductivity.3. The three chiral metal complexes were resolved successfully with chemical methods using disodium 0,0 -dibenzoyl-D-tartrate and disodium 0,0 -dibenzoyl-L-tartrate as the resolving agent, and their optical rotation values were measured. The optical rotation values are stable during the mesurment.4. The characteristics of the interaction of the complexes [Ru(bpy)2DMNP]2+ and [Ru(bpy)2BOPIP]2+ with CT-DNA were examined by Ultra-visible absorption spectra, fluorescent spectra, viscosity measurements , cyclic voltammetry and molecular modeling. [Ru(bpy)2BOPIP]2+ is a novel complex, whereas [Ru(bpy)2DMNP]2+ has been reported . We gave a further study on the interaction of Ru(bpy)2DMNP]2+ with CT-DNA using DNA melting experiment, photochemistry, viscosity measurements and cyclic voltammetry. The following have been learnt from this study:The binding of the complexes to DNA will cause "hypochromic effect " in UV absorption, enhancement in the luminescence, and increase of DNA viscosity. The changes observed are characteristic of intercalation. The greater increase in luminescence seen for the A-isomer in the presence of DNA over that for the A-isomer indicated that the DNA-binding of the A-isomer is stronger than that of the A-isomer. The result was also identified by viscosity measurements. Molecular modeling of normal B-DNA by the two complexes were also examined, the caculating results provided further evidence for the interaction of the complexes with DNA.5. We selected [Ru(bpy)2DMNP]2+, [Ru(bpy)2BOPIP]2+ and their individual enantiomers for the study of cleavage plasmid pBR 322 DNA by gelelectrophoresis technique. The results showed upon irradiation at 365 nm, the two complexes all can promote the cleavage of plasmid pBR 322 DNA from supercoiled form I(ccc) to nicked form II(oc), but [Ru(bpy)2DMNP]2+ is more efficiently. The results also reflect obvious enantioselectivities on DNA cleavage were found for [Ru(bpy)2DMNP]2+. For each set of isomers, the cleavage mechanisms were the same. The active oxygen species of DNA cleavage by these complexes is singlet molecular oxygen('O2).