The photochemistry of the (7-methoxycoumarin-4-yl)methyl (MCM) carboxylates 3a − d, the mesylate 4, and the phosphates 5a − e has been examined under near physiological conditions in acetonitrile or methanol/aqueous HEPES buffer solution, respectively. Analysis of photoproducts as well as measurements of photochemical quantum yields, fluorescence quantum yields, and lifetimes for the excited singlet state verified the similar photochemical and photophysical behavior of all the esters studied here. 4-(Hydroxymethyl)-7-methoxycoumarin (2) and the corresponding free acids were obtained as major products upon irradiation. The rates of deactivation of the excited MCM derivatives 3a − 5e were found to be dependent on the leaving group ability of the anion concerned as well as on the solvent polarity. The polarity dependence and the exclusive formation of 18O-labeled 2 during irradiation of 5a in 18O-labeled water indicate that photocleavage of the excited singlet state of the MCM caged compounds 3a − 5e proceeds via a photo SN1 mechanism (solvent-assisted photoheterolysis).

(Coumarin-4-yl)methyl esters (CM-A) are caged compounds that, upon excitation, release the masked biologically active acid HA and the highly fluorescent (coumarin-4-yl)methyl alcohol CM-OH very rapidly and in part with high efficiency. The results of photostationary and time-resolved investigations of 25 CM-A esters and corresponding CM-OH alcohols with varying substitution on the (coumarin-4-yl)methyl moiety and a wide variation in the structure of the acidic part have been analyzed. The initial step of the photoreaction is heterolytic ester cleavage leading to the singlet ion pair 1[CM+ A-] with rate constant k1. 1[CM+ A-] hydrolyzes to CM-OH and HA with rate constant k2 or recombines to ground-state CM-A with rate constant krec. 1[CM+ A-] is the key intermediate of the reaction. Stabilization of both CM+ by using electron-donating substituents and A- by increasing the acid strength leads to a strong enhancement of k1 and simultaneously to a diminution of krec. Therefore, stabilization of the ion pair has a two-fold positive effect on the photocleavage of (coumarin-4-yl)methyl esters: increasing the rate of the initial reaction step, which might require less than 30 ps, and increasing the efficiency of product formation.

A series of axial and equatorial diastereomers of (coumarin-4-yl)methyl-caged adenosine cyclic 3',5'-monophosphates (cAMPs), 1-6, having methoxy, dialkylamino, or no substituent in the 6- and/or 7-positions, and their corresponding 4-(hydroxymethyl)coumarin photoproducts 7-12 have been synthesized. The photochemical and UV/vis spectroscopical properties (absorption and fluorescence) of 1-6 and 7-12 have been examined in methanol/aqueous HEPES buffer solution. Donor substitution in the 6-position causes a strong bathochromic shift of the long-wavelength absorption band, whereas substitution in the 7-position leads only to a weak red shift. The photochemical cleavage of the caged cAMPs was investigated, and the photoproducts were analyzed. Photochemical quantum yields, fluorescence quantum yields, and lifetimes of the excited singlet states were determined. The highest values of photochemical quantum yields (photo-S(N)1 mechanism) were obtained with caged cAMPs having a donor substituent in the 7-position of the coumarin moiety, caused by electronic stabilization of the intermediately formed coumarinylmethyl cation. With donor substitution in the 6-position, the resulting moderate electronic stabilization of the coumarinylmethyl cation is overcompensated by the strong bathochromic shift, reducing the energy gap between the excited-state S(1) and the corresponding coumarinylmethyl cation. The rate constant for the ester cleavage and liberation of cAMP is about 10(9) s(-1), estimated for the axial isomer of 6 by analysis of the fluorescence increase of the alcohol 12 formed upon laser pulse photolysis.

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