A Photolabile Ligand for Light-Activated Release of Caged Copper

Abstract

A photosensitive caged copper complex has been prepared from a tetradentate ligand (H2cage) composed of two pyridyl-amide arms connected by a photoreactive nitrophenyl group. H2cage binds Cu2+ in aqueous solution with a stability constant (log beta) of 10.8, which corresponds to a KD of 16 pM at pH 7.4. The neutral Cu2+ complex, [Cu(OH2)(cage)], crystallizes as a distorted trigonal bipyramid coordinated by two amide and two pyridyl N atoms, with a water molecule bound in the trigonal plane. Photolysis with 350 nm UV light cleaves the ligand backbone to release photoproducts with significantly diminished affinity for Cu2+, thereby uncaging the metal ion. When coordinated as the caged complex, copper has diminished reactivity to produce hydroxyl radicals from Fenton-like reaction mixtures containing hydrogen peroxide and ascorbic acid. Postphotolysis, uncaged copper promotes hydroxyl radical formation under the same conditions. The strategy of caging copper is promising for applications where light could be used to trigger release of copper as a pro-oxidant to increase oxidative stress or as a tool to release copper intracellularly to study mechanisms of copper trafficking.

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light

“…32,35,53,55,56 A wide-variety of photo-uncaging compounds have been reported based on o -nitrobenzyl, o -nitro-phenethyl, indoline, quinoline, amino-coumarin, perylene, nitrophenyl, nitrophenyl-propyloxy compounds, ruthenium photocages, nitrodibenzofuran (NDBF), boron-dipyrromethene derivatives, and so forth. 35,53,55–58 Nanocarriers including gold (Au) NPs, 59 micelles, 60 liposomes, 61 and peptide-based nanocarriers 35 have been reported to demonstrate photocaging/uncaging behavior. Various cargos such as thiols, 35 platinum(II) complexes, 57 diphospho-myo-inositol pentakisphosphates (InsP 7 ), 62 cyclooxygenase-2 enzyme inhibitors, 63 copper complexes, 58 and anticancer drugs/prodrugs (e.g., camptothecin, coumarin, 5-fluorouracil, doxorubicin (DOX)) 43,59,60,64 have been shown to be protected and carried by the photocaging nanocarriers.…”

“…35,53,55–58 Nanocarriers including gold (Au) NPs, 59 micelles, 60 liposomes, 61 and peptide-based nanocarriers 35 have been reported to demonstrate photocaging/uncaging behavior. Various cargos such as thiols, 35 platinum(II) complexes, 57 diphospho-myo-inositol pentakisphosphates (InsP 7 ), 62 cyclooxygenase-2 enzyme inhibitors, 63 copper complexes, 58 and anticancer drugs/prodrugs (e.g., camptothecin, coumarin, 5-fluorouracil, doxorubicin (DOX)) 43,59,60,64 have been shown to be protected and carried by the photocaging nanocarriers. The light irradiation has ranged from NIR, 63,65,66 to UV 58 to visible light, 55,67 and using mechanisms such as two photon excitation, 63,68,69 upconversion by UCNPs, 64 or simple one photon excitation 70 can be employed to induce uncaging of the photolabile protecting groups.…”

Application of Metal Coordination Chemistry To Explore and Manipulate Cell Biology

“…In an effort to broaden the applicability of caged metals beyond calcium, our group recently introduced a photo-cleavable pyridal amide ligand that binds to Cu 2+ with an apparent K D at pH 7.4 of 16 pM ([Cu(OH 2 )(cage)], 18 ) 119. Photolysis of caged copper with 360 nm UV light cleaves the tetradentate ligand to give photoproducts that have only bidentate chelating ability and therefore a reduced affinity for copper.…”

Protein-Ligand Interactions and Allosteric Regulation of Activity in DREAM Protein

“…These differences likely arise from distinct solvation shells around Tb 3+ and Ca 2+ in bulk water as well as a due to a distinct structural organization of the Tb 3+ :DM-nitrophen complex (Martin, Richardson 1979). Similar isotherms and thermodynamic parameters were observed for Tb 3+ displacement of Ca ) (Kaplan, Ellis-Davies 1988), can be used to calculate the affinity of Tb 3+ ions for DM-nitrophen using (Sigurskjold 2000): The last cage compound studied is a Cu 2+ chelating photosensitive compound synthetized by the group of Dr. Kavalieratos at FIU (Ciesienski et al 2008). The thermodynamic parameters were determined from a linear plot using eqn.…”

“…The synthesis of the H2Cage and Cu(OH2)Cage compounds were performed in the laboratory of Dr. Konstantinos Kavallieratos at FIU and were done according to the procedure reported by Ciesienski et al (2008). The purity was verified by H 1 NMR (400 MHz Bruker NMR spectrometer) and IR (Nicolet Magna-IR 560 spectrometer) spectroscopy.…”