Studies On The Construction Of Trifluoromethylated N-heterocyclic Complexes And Interaction With BSA/DNA

The study of the binding activity of trifluoromethylpyridine carboxylic acid complexes with calf thymus DNA(CT-DNA).bovine serum albumin(BSA)beneficial to the development of new chemical nuclease and DNA,BSA structural probes.It could be a certain theoretical guiding significance for designing and synthesising the new fluorinated drugs as well.The main study of this paper as follows:1?Preparation of 11 complexes with different transition metal ions(M=M=Co2-?Cu2+?Zn2-?Cd2+?Mn2+?Ni2+)via solution,diffusion and hydrothermal methods based on 5-(trifluoromethyl)pyridine-2-carboxylic acid(Htpc)and 4-trifluoromethylnicotinic acid(Htfc).Then,the structures were confirmed through elemental analysis,infrared spectral analysis,thermogravimetric analysis and X-ray single-crystal diffraction.2?The optimized geometric structures of the ligands(Htpc.Htfc)were determined using the M06-2X functional of density functional theory(DFT)with the 6-311+G(d,p)basis set.And the energy values of their LUMO and HOMO orbitals,the difference(AE),the ionization potential(I),the electron affinity(A),the chemical hardness(?)and the softness(S)have been calculated.These parameters indicate that chemical reactivity of Htpc is slightly stronger than Htfc,while the chemical stability is less lower than Htfc.3?The binding activities of Htpc,Htfc and complex 1-11 with bovine serum albumin(BSA)were studied by fluorescence and UV-Vis absorption spectroscopy.The results of fluorescence spectra show that all the tested compounds can quench the fluorescence of BSA and were all static quenching process.At the same time,the UV-Vis absorption spectra also have significant hyperchromic effect,which further proved that the conclusion was correct.In addition,the bonding activity of complex 1-6 was stronger than that of 7-11 since the coordination mode of 1-6 is N-O chelation mode,which could be enhance the co-planarity and rigidity of the structure facilitating the binding affinity with BSA.Compared to other complexes based on pyridinecarboxylic acid and its derivatives,complexes 1-11 exhibited higher binding affinity with BSA.It may attributed to the introduction of trifluoromethyl group increasing the lipophilic character of complexes 1-11.4?The binding activities of Htpc,Htfc and complex 1-11 with CT-DNA were also studied by fluorescence and UV-Vis absorption spectroscopy.The UV-Vis absorption spectra showed that the absorbance intensity of the tested compounds showed hypochromicity and redshift with the increasing of CT-DNA concentration,which preliminarily indicated that the tested compounds were combined with CT-DNA through embedding mode.The fluorescence spectra showed that the intensity of the system decreased with the test compounds continuously added to the EB-DNA system declaring that the test compounds could displace the EB molecules.Since the EB molecule is a typical intercalation agent,which further proved that the test compounds could be combined with CT-DNA through the embedding mode.The Htpc and Htfc displayed weaker binding affinity to CT-DNA than their corresponding complexes,while the bonding activity of complexes 1-6 were stronger than that of complexes 7-11.All in all,the 11 complexes showed good binding activity with BSA and DNA due to the introduction of trifluoromethyl group in the structure,which increased the lipophilicity of the complexes.It could be a certain theoretical guiding significance for designing and synthesising a new fluorinated drugs.