Design, synthesis and application of metal cages based on 4,5-dimethoxy-2-nitrobenzyl (DMNB) utilizing macrocyclic and acyclic receptors for biological relevant metal ions

Date of Completion

January 2012

Keywords

Chemistry, Biochemistry

Degree

Ph.D.

Abstract

Recent investigations have shifted the focus of Cu+ from a static component of the cellular machinery to a dynamic effector in cellular signaling cascades. At present, there are no means available to facilitate the studies on how Cu+ is involved in these cellular signaling mechanisms. The ability to generate small, well-defined concentrations of Cu+ would facilitate these studies; however, achieving controlled release of Cu+ with currently available techniques is impossible. We have synthesized a caged-Cu+ complex, CuproCleav-1, to overcome this limitation. CuproCleav-1 release Cu+ upon irradiation, which provides a facile and convenient technique to control the spatial and temporal concentration of Cu+ necessary for cell studies. The CuproCleav-1 cage consists of a thioether chelating ligand and 4,5-dimethoxynitrobenzyl photoactive chromophore. Irradiation of the Cu +-cage results in fracture of the ligand backbone, which releases Cu+ within physiologically relevant conditions. ^ CrownCast cages have been synthesized to broaden the scope of uncaging strategy for divalent metal ions. CrownCast cages combines N-phenylazamacrocyclic or acyclic receptor with 4,5-dimethoxynitrobenzyl chromophore. The uncaging mechanism of these complexes involves a photoreaction that converts the nitrobenzohydrol, which is para to the aniline nitrogen into the corresponding nitrosobentophenone. Resonance delocalization of the aniline to the distal carbonyl of the photoproducts attenuates the ability of the nitrogen to interact with the cation. CrownCast-1 utilizes a 13-phenyl-1,4,7,10-tetraoxa-13-azacyclopentadecane (A15C5) receptor showed a modest selectivity for Ca2+ but a better cage for Mg2+. CrownCast-2 utilizes a 10-phenyl-1,4-dioxza-7,1,3-dithia-10-azacyclopentadecane (AT215C5) showed selectivity for Hg2+ in aqueous solution. CrownCast-3 utilizes a 16-phenyl-1,4,7,10,13-pentaoxa-16-azacyclooetadecane (A18C6) for Pb2+ selectivity. ArgenCast-1 utilizing 9-phenyl-3,6,12,15-tetrathia-9-azaheptadecane acyclic ligand have a good affinity for Ag+. Uncage ligands have a lower metal affinity than the caged o-nitrobezyhydrol ligands. ^ A new methodology of electrophilic aromatic iodination on aniline derived CrownCast receptors using a unique complex {[K.18-C-6]ICl2} n was also developed as an alternative synthetic method. The trihalide anion, ICl2−, is supported by an 18-crown-6 macrocycle forming a coordinating polymer in the solid state. Controlled mono-iodination with anilines was achieved while poly-iodination was observed with phenols. ^

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