Investigation of self-immolative linkers in the design of hydrogen peroxide activated metalloprotein inhibitors
A series of self-immolative boronic ester protected methyl salicylates and metal-binding groups with various linking strategies have been investigated for their use in the design of matrix metalloproteinase proinhibitors.
Jourden, Jody L. Major,Daniel, Kevin B.,Cohen, Seth M.
supporting information; experimental part
p. 7968 - 7970
(2011/08/07)
Enzymatic activation of a matrix metalloproteinase inhibitor
Matrix metalloproteinase inhibitors (MMPi) possessing a glucose protecting group on the zinc-binding group (ZBG) show a dramatic increase in inhibitory activity upon cleavage by β-glucosidase.
Major Jourden, Jody L.,Cohen, Seth M.
experimental part
p. 1241 - 1243
(2010/06/15)
Hydrogen peroxide activated matrix metalloproteinase inhibitors: A prodrug approach
(Figure Presented) Doing double duty: A metalloproteinase inhibitor that can be activated by reactive oxygen species (ROS) has been designed to protect the blood-brain barrier (BBB) in ischemic reperfusion injury. By both neu-tralizing damaging ROS and inhibiting degradative metalloproteinases, a single compound can eliminate both threats to the BBB upon activation.
Major Jourden, Jody L.,Cohen, Seth M.
supporting information; experimental part
p. 6795 - 6797
(2010/12/19)
Competitive occurrence of homolytic N-O and heterolytic C-O bond cleavage in excited-state 1-(arylmethyloxy)-2-pyridones
The irradiation at 340 nm of the title compounds having 9-anthryl and pyren-1-yl groups in methanol was found to give the heterolytic C-O bond cleavage products: 1-hydroxy-2-pyridone and aryl-substituted dimethyl ether (which predominate for the reaction of the former title compound) in addition to 2-pyridone, aryl-substituted methanol and aryl-substituted formaldehyde derived from the homolysis of the N-O bond (which mainly occurs in the photolysis of the latter title compound). It was also found that substitution of the methyl group for hydrogen at the 6-position of the pyridone skeleton in 1-(9-anthrylmethyloxy)-2-pyridone decreases the relative composition of the arylsubstituted dimethyl ether to some extent. These substituent effects on the product compositions were explained in terms of stereoelectronic effects on a charge transfer-type interaction between the aromatic and pyridone rings in the singlet excited state. Analyses of the ground-state conformation for the title compounds by MM2 calculations and 1H NMR spectroscopy, as well as of their singlet excited-state behaviour, substantiated the existence of a non-emissive intramolecular exciplex intermediate which plays a key role in inducing the C-O bond heterolysis.
Photoinduced heterolysis of the carbon-oxygen bond in bichromophoric 1- arylmethyloxy-2-pyridones
Irradiation of the title compound having a 9-anthryl (1a) or a 1- pyrenyl group (1b) in methanol was found to give the heterolytic C-O bond cleavage products: 1-hydroxy-2-pyridone and arylmethyl methyl ether, (which predominate for the reaction of 1a), along with 2-pyridone, aryl-substituted methanol and aryl aldehyde derived from the homolysis of the N-O bond (that mainly occurs in the photolysis of 1b). Spectroscopic analysis of the ground- state and excited singlet-state behavior of 1 revealed that a non-emissive intramolecular exciplex (whose formation rate is much faster in 1a than in 1b) plays a key role in inducing the C-O bond heterolysis.