Substituted dipyridophenazine complexes of Cr(iii): Synthesis, enantiomeric resolution and binding interactions with calf thymus DNA

Abstract

[Cr(phen) 2 (X 2 dppz)] 3+ {X = H, Me, or F} have been synthesised, characterised, and chromatographically resolved into their constituent D and K enantiomers. The DNA-binding interactions of each of the racemic complexes were investigated, with the results of linear dichroism, thermal denaturation, and emission quenching studies indicative of intercalative binding to CT-DNA with a significant electrostatic contribution. UV/Vis absorption titrations suggest strong DNA binding by each of the racemic complexes, with the methylated analogue [Cr(phen) 2 (Me 2 dppz)] 3+ exhibiting the largest equilibrium binding constant. Emission quenching and UV-Vis titrations of the enantiomers of [Cr(phen) 2 (dppz)] 3+ imply similar binding affinities for the D and K isomers, although significant differences between the circular dichroism spectra of the enantiomers in the presence of DNA connote differences in binding orientation and/or conformation between the two.

Excited state behaviour of substituted dipyridophenazine Cr(iii) complexes in the presence of nucleic acids

“…We can therefore conclude that it is guanine bases in the DNA which act as efficient quenchers. Steady state emission experiments 32 show that the phosphorescence is more than 97% quenched at P/D > 12 for all complexes, consistent with a very low quantum yield of emission for bound complexes. However, only 42% of CTDNA base pairs contain guanine 37 so that one might expect to a first approximation that 34% of the intercalative binding sites would consist of only AT base-pairs and 67% have at least one GC base-pair.…”

“…32 Briefly 3 were synthesised by refluxing the triflato complex with a small excess of the X 2 dppz ligand of choice for approximately 18 h. The yellow product was collected by suction filtration and purified by lipophilic and/or cation-exchange chromatography. Other chemicals used in this study -calf thymus DNA (CT-DNA), mononucleotides (5′-GMP, 5′-AMP), and Na 2 HPO 4 ·12H 2 O, NaH 2 PO 4 ·2H 2 O (for phosphate buffer preparation) -were purchased from Sigma Aldrich and used without further purification.…”

“…32,45 Since the excited state oxidizing power of all three complexes are relatively high (1.52 V, 1.49 V and 1.62 V versus NHE for X = H, Me and F, respectively) it was proposed that electron transfer is the most likely mechanism for the observed quenching. In order to obtain support for this hypothesis we have examined the behaviour of the excited states of all three complexes with guanosine-5′-monophosphate (GMP), adenosine-5¢-monophosphate (AMP) and calf thymus deoxyribonucleic acid (CT-DNA).…”

“…In an effort to modulate DNA binding constants and spectroscopic properties we have recently synthesised a family of chromium complexes [Cr(phen) 2 (X 2 dppz)] 3+ {X = H, Me, or F} and resolved each into their enantiomers. 32 In this previous study we showed that despite the energy of the metal centered excited state being unaffected by the substitution of the dppz ligand, the excited state of the difluoro species is a significantly stronger oxidising agent than both the unsubstituted and the dimethyl species. We also provided evidence that the new complexes bind to calf thymus DNA (CT-DNA) via intercalation and that the dimethyl derivative has the higher binding affinity.…”

Heteroleptic chromium(III) tris(diimine) [Cr(N^N)2(N′^N′)]3+ complexes

“…We have extended the study to heteroleptic tris(diimine) [Cr(N^N) 2 (N'^N')] 3+ complexes and have embarked on a structural investigation of these complexes to probe the influence of the ligand set on the metal environment. Although the complexes [Cr(bpy) 3 ] 3+ (bpy = 2,2'-bipyridine) and [Cr(phen) 3 ] 3+ (phen = 1,10-phenanthroline) are well known [4], synthetic and structural studies of heteroleptic complexes remain sparse [5,6,7,8] [10]. These are easily replaced by the second ligand N'^N' [11].…”