Photochemical Reaction Mechanisms of 2-Nitrobenzyl Compounds:  Methyl Ethers and Caged ATP

Abstract

The mechanism of methanol photorelease from 2-nitrobenzyl methyl ether (1) and 1-(2-nitrophenyl)ethyl methyl ether (2), and of ATP release from adenosine-5'-triphosphate-[P(3)-(1-(2-nitrophenyl)ethyl)] ester ('caged ATP', 3) was studied in various solvents by laser flash photolysis with UV-vis and IR detection. In addition to the well-known primary aci-nitro transients (A, lambda(max) approximately 400 nm), two further intermediates preceding the release of methanol, namely the corresponding 1,3-dihydrobenz[c]isoxazol-1-ol derivatives (B) and 2-nitrosobenzyl hemiacetals (C), were identified. The dependencies of the reaction rates of A-C on pH and buffer concentrations in aqueous solution were studied in detail. Substantial revision of previously proposed reaction mechanisms for substrate release from 2-nitrobenzyl protecting groups is required: (a) A novel reaction pathway of the aci-tautomers A prevailing in buffered aqueous solutions, e.g., phosphate buffer with pH 7, was found. (b) The cyclic intermediates B were identified for the first time as the products formed by the decay of the aci-tautomers A in solution. A recently proposed reaction pathway bypassing intermediates B (Corrie et al. J. Am. Chem. Soc., 2003, 125, 8546-8554) is shown not to be operative. (c) Hemiacetals C limit the release rate of both 1 (pH < 8) and 2 (pH < 10). This observation is in contrast to a recent claim for related 2-nitrobenzyl methyl ethers (Corrie et al.). Our findings are important for potential applications of the 2-nitrobenzyl protecting group in the determination of physiological response times to bioagents ('caged compounds').

Photochemical electrocyclic ring closure and leaving group expulsion from N-(9-oxothioxanthenyl)benzothiophene carboxamides

“…In addition, the 1 H NMR NOESY showed cross peaks establishing the close spatial proximity of a 10 proton ortho to the thioxanthone carbonyl group and the C-4 and C-5 protons of the benzothiophene benzene ring. The acid photoproduct 27 did not have sufficient solubility in aqueous solvent to obtain the 13 C NMR spectrum, and since it was only obtainable as a powder, the X-ray structure also could not be 15 determined …”

“…, and 10 (LG -= Cl -) 50 mL of 15 water was added to the photolysate, and the diluted photolysate was extracted four times with 30 mL of CH 2 Cl 2 . The combined extracts were washed twice with 30 mL water, brine, and concentrated in vacuo.…”

“…4 Carboxanilides 5 were found to release various leaving groups LG -that vary in basicity in essentially quantitative yields. Because of the potentially modular chromophore (ring A) and the ability of the putative zwitterionic intermediate to release relatively basic leaving groups such as thiolates 5,7 and 5 (1) 10 phenolates 8 , i.e., side-chain groups of cysteine and tyrosine residues in peptides and proteins, the photochemical electrocyclic ring closure approach to the generation of zwitterionic 15 intermediates appeared to be promising. In this paper we extend the absorption maximum of the chromophoric group to 385 nm by use of the thioxanthone chromophore as ring A, as shown for benzothiophene carboxamides 7-10.…”

“…In both cases the direct photolyses result in expulsion of the various LG -in nearly quantitative yields, regardless of basicity of the LG -. As with 5, 15 the photochemical mechanism for 7-9 is thought to involve expulsion of a leaving group LG -from a zwitterionic intermediate phydroxyphenacyl λ max 282 nm (ε 14,000), 17 and desyl λ max 323 nm (ε 400). 18 A long wavelength absorber is 25 aminocoumarinylmethyl λ max 402 nm (ε 18,600).…”

Conformational dynamics associated with calcium binding to calcium transducers

“…The reaction mechanism for the photorelease of the protected moiety from 2-nitrobenzyl compounds have been previously studied using determined R, time-resolved absorption spectroscopy and computational methods (Cheng et al 2002, Gaplovsky et al 2005, Ill'ichev et al 2004. The mechanism is shown in Scheme 2.…”