title: Supramolecular host-guest interaction of trityl-nitroxide biradicals with cyclodextrins: modulation of spin-spin interaction and redox sensitivity.
abstract: Supramolecular host-guest interactions of trityl-nitroxide (TN) biradicals CT02-VT, CT02-AT and CT02-GT with methyl-β-cyclodextrin (M-β-CD), hydroxypropyl-β-cyclodextrin (H-β-CD) and γ-cyclodextrin (γ-CD) were investigated by EPR spectroscopy. In the presence of cyclodextrins (i.e., γ-CD, M-β-CD and H-β-CD), host-guest complexes of CT02-VT are formed where the nitroxide and linker parts possibly interact with the cyclodextrins' cavities. Complexation with cyclodextrins leads to suppression of the intramolecular through-space spin-spin exchange coupling in CT02-VT, thus allowing the determination of the through-bond spin-spin exchange coupling which was calculated to be 1.6 G using EPR simulations. Different types of cyclodextrins have different binding affinities with CT02-VT in the order of γ-CD (95 M(-1)) > M-β-CD (70 M(-1)) > H-β-CD (32 M(-1)). In addition, the effect of the linkers in TN biradicals on the host-guest interactions was also investigated. Among the three TN biradicals studied, CT02-VT has the highest association constant with one designated cyclodextrin derivative. On the other hand, the complexes of CT02-GT (∼ 22 G) and CT02-AT (7.7-9.0 G) with cyclodextrins have much higher through-bond spin-spin exchange couplings than those of CT02-VT (1.6 G) due to the shorter linkers than those of CT02-VT. Furthermore, the stability of TN biradicals towards ascorbate was significantly enhanced after the complexation with CDs, with an almost 2-fold attenuation of the second-order rate constants for all the biradicals. Therefore, the supramolecular host-guest interactions with cyclodextrins will be an alternative method to modulate the magnitude of the spin-spin interactions and redox sensitivity of TN biradicals, and the resulting complexes are promising as highly efficient DNP polarizing agents as well as EPR redox probes.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. songyuguang@tmu.edu.cn.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tan
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. songyuguang@tmu.edu.cn.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. songyuguang@tmu.edu.cn.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital, Gannan Medical University, Jiangxi 341000, P. R. China. awen7758ilu@163.com.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Institute of Materials and Environmental Chemistry, Hungarian Academy of Sciences and, Department of Physics, Budapest University of Technology and Economics, Budafoki ut 8, 1111 Budapest, Hungary.
authors.forename: Antal
authors.initials: A
authors.lastname: Rockenbauer
authors.affiliation: Center for Biomedical EPR Spectroscopy and Imaging, The Davis Heart and Lung Research Institute, THE Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA. liuyangping@tmu.edu.cn and Department of Pharmacology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Villamena
authors.affiliation: Center for Biomedical EPR Spectroscopy and Imaging, The Davis Heart and Lung Research Institute, THE Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA. liuyangping@tmu.edu.cn.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. songyuguang@tmu.edu.cn and Center for Biomedical EPR Spectroscopy and Imaging, The Davis Heart and Lung Research Institute, THE Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA. liuyangping@tmu.edu.cn.
authors.forename: Yangping
authors.initials: Y
authors.lastname: Liu
mesh_terms: D003505:Cyclodextrins / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D003505:Cyclodextrins; D005609:Free Radicals; D046911:Macromolecular Substances; D009589:Nitrogen Oxides