摘要
The interactions between the new organometallic complexes, ferrocenesubstituted dithioocarborane conjugates （denoted as FcSB1, FcSB2 and FcSBCO） and hemoglobin （Hb） are investigated by electrochemistry, fluorescence and UVvis absorption spectroscopy. The results demonstrate that FcSB1, FcSB2 and FcSBCO can bind to the heme iron center through the replacement of the weakly bound H20/02 in the distal heme pocket of Hb by their sulfur donor atoms, inducing the allosteric change from the R state （oxygenated conformation, relax） to T state （deoxygenated conformation, tense）. The binding affinity is in the order of FcSBCO〉FeSB2〉FeSB1. Moreover, the fluorescence study illustrates that the three ferrocenecarborane conjugates differently affect the quarterly and tertiary structures as well as the polarity in the surrounding of the Trp and Tyr residues in Hb. Typically, FcSB2 mainly induces alterations of the microenvironment around the 1337Trp residue which is located on the cql32 interface of Hb. Such distinct influences are attributed to the structural features of FcSB1, FcSB2 and FcSBCO containing hydrophobic ferrocenyl and carboranyl units as well as C=O group. Screening the proteinbinding behavior can signify the potential bioactivity of such molecules and may be helpful in the future development of promising multifunctional metallodrugs.
The interactions between the new organometallic complexes, ferrocene-substituted dithio-o-carborane conjugates (denoted as FcSB1, FcSB2 and FcSBCO) and hemoglobin (Hb) are investigated by electrochemistry, fluorescence and UV-vis absorption spectroscopy. The results demonstrate that FcSB1, FcSB2 and FcSBCO can bind to the heme iron center through the replacement of the weakly bound H2O/O2 in the distal heme pocket of Hb by their sulfur donor atoms, inducing the allosteric change from the R state (oxygenated conformation, relax) to T state (deoxygenated conformation, tense). The binding affinity is in the order of FcSBCO>FcSB2>FcSB1. Moreover, the fluorescence study illustrates that the three ferrocene-carborane conjugates differently affect the quarterly and tertiary structures as well as the polarity in the surrounding of the Trp and Tyr residues in Hb. Typically, FcSB2 mainly induces alterations of the microenvironment around the β37Trp residue which is located on the α1β2 interface of Hb. Such distinct influences are attributed to the structural features of FcSB1, FcSB2 and FcSBCO containing hydrophobic ferrocenyl and carboranyl units as well as C=O group. Screening the protein-binding behavior can signify the potential bioactivity of such molecules and may be helpful in the future development of promising multifunctional metallodrugs.
作者
WU ChunHui1,3, YE HongDe2, JIANG Hui1, WANG XueMei1 & YAN Hong2 1State Key Lab of Bioelectronics (Chien-Shiung Wu Lab), Southeast University, Nanjing 210096, China 2State Key Laboratory of Coordination Chemistry
School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China 3School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China
基金
supported by the National Basic Research Program of China (2010CB732404, 2010CB923303)
the National Natural Science Foundation of China (21175020, 90713023, 20925104)
the Project of High Technology Research and Development Program of China (2007AA022007)
Gongdong Province (2011B090400357)
the Natural Science Foundation of Jiangsu Province (BK2008149, BK2010052)
C. W. acknowledges the Fundamental Research Funds for the Central Universities (ZYGX2011J099)
the support by the Open Research Fund of State Key Laboratory of Bioelectronics, Southeast University (2011E09)
