8-或6-(3-氯苯甲酰)香豆素衍生物的合成、表征、生物活性及与牛血清白蛋白的相互作用

合成了2个新化合物7-羟基-8-(3-氯苯甲酰基)-4-甲基香豆素(1)和7-羟基-6-(3-氯苯甲酰基)-4-甲基香豆素(2).X射线单晶衍射分析表明,2个化合物的晶体同属于单斜晶系,P21/c空间群,化合物1:a=1.21527(14)nm,b=1.01550(12)nm,c=1.5045(2)nm,β=112.377(2)°,V=1.7169(4)nm3,Dc=1.396 g/cm3,Z=4,F(000)=752,R1=0.0415,wR2=0.0981I>2σ(I)],S=1.063;化合物2:a=2.0168(2)nm,b=0.76229(12)nm,c=2.25497(17)nm,β=123.987(6)°,V=0.8745(6)nm3,Dc=1.454 g/cm3,Z=8,F(000)=1296,R1=0.0604,wR2=0.1384I>2σ(I)],S=0.948.抗菌实验结果表明,2个化合物对大肠杆菌(E.coli)、枯草杆菌(B.subtilis)和金色葡萄球菌(S.aureus)均有中等程度的抑制作用;体外抗氧化实验结果表明,2个化合物对超氧阴离子自由基(O2-.)、羟基自由基(.OH)和二苯代苦味肼基自由基(DPPH.)均有良好的清除能力.采用荧光光谱法研究了不同温度下2个化合物与牛血清白蛋白(BSA)的相互作用,结果表明,2个化合物对BSA的荧光猝灭均属于静态猝灭;热力学数据表明,化合物1(ΔH>0,ΔS>0,ΔG<0)与BSA主要以疏水作用力相结合,化合物2(ΔH<0,ΔS<0,ΔG<0)与BSA主要以氢键或范德华力相结合;BSA与化合物1和化合物2间的距离分别为2.59和2.38 nm,说明2个化合物与BSA之间可能发生了非辐射能量转移.

Synthesis,Characterization,Biological Activity and Interaction with Bovine Serum Albumin of 8-or 6-(3-Chlorobenzoyl)coumarin Derivatives

Two new compounds, 4-methyl-7-hydroxy-8-(3-chlorobenzoyl)coumarin(1) and 4-methyl-7-hydroxy-6-(3-chlorobenzoyl)coumarin(2), were synthesized and characterized by elemental analysis, infrared spectra, 1H NMR and single crystal X-ray diffraction methods. The crystals of compounds 1 and 2 belong to monoclinic system with space group P21/c, compound 1: a=1.21527(14) nm, b=1.01550(12) nm, c=1.5045(2) nm, β=112.377(2)°, V=1.7169(4) nm3, Dc=1.396 g/cm3, Z=4, F(000)=752, R1=0.0415, wR2=0.0981I>2σ(I)], S=1.063; compound 2: a=2.0168(2) nm, b=0 .76229(12) nm, c=2.25497(17) nm, β=123.987(6)° , V=0.8745(6) nm3, Dc=1.454 g/cm3, Z=8, F(000)=1296, R1=0.0604, wR2=0.1384I>2σ(I)], S=0.948. The results of antibacterial experiment showed that the title compounds had the activity for inhibiting growth of E. coli, B. subtilis and S. aureus. The antioxidation acti-vity of the title compounds were investigated by the O2-·, DPPH· and ·OH methods. The results showed that the title compounds had strong antioxidation activity. The interactions of title compounds and bovine serum albumin(BSA) were investigated by fluorescence spectroscopy at different temperatures. The results indicated that the title compounds caused the fluorescence quenching of BSA through a static quenching procedure. The corresponding thermodynamic parameters enthalpy change(ΔH), entropy change(ΔS), Gibbs free energy change(ΔG), between the title compounds and BSA were calculated. The interaction between the compound 1(ΔH>0, ΔS>0, ΔG<0) and BSA was driven mainly by hydrophobic force, whereas the interaction between compound 2(ΔH<0, ΔS<0, ΔG<0) and BSA was driven mainly by hydrogen bond force or van der Waals force. The binding average distance r between the donor(BSA) and acceptors(compounds 1 and 2) were obtained to be 2.59 and 2.38 nm, respectively, based on the Föster's theory, which indicate the energy transfer can occur from BSA to title compounds with high probability.