Excited states of skin-sensitizing coumarins and psoralens. Spectroscopic studies

Abstract

Several skin-sensitizing psoralens and their model coumarins fluoresce weakly and phosphoresce relatively strongly. The excited states of some of these molecules have been investigated in rigid matrices at 12 and 77 °K by means of luminescence and photoselection measurements. Coumarins and psoralens exhibit a relatively high phosphorescence to fluorescence ratio ( / > 1); however, in coumarylpyrone (benzo[l,2-6:4,5-6']dipyran-2,8-dione) and coumarins with strong charge transfer substituents, the ratio is significantly less than unity. In coumarylpyrone this is interpreted as being due to a decreased efficiency of the intersystem crossing from 8 ( , *) to ( , *) as a consequence of the lowering in energy of the ( , *) state below the 3( , *) state. For the series of molecules investigated, it was established that the 0-0 phosphorescence frequencies, ¡Vo, are essentially independent of substituents or the extent of conjugation. This result reinforces the model of energy localization in the 3( , *) state as proposed previously for coumarin and psoralen. The electronic structures of the excited states of selected compounds calculated by SCF-MO methods are consistent with this model. The MO data as well as the spectroscopic data may be correlated with the photobiological reactivity of these molecules toward DNA.Coumarins, particularly psoralens, are known to photosensitize skin erythema and skin cancer in mice and guinea pigs, though skin cancer in man is not unequivocally established.3•4 56The skin-sensitizing potency of psoralens has been correlated with their photoreactivity toward pyrimidine bases of DNA via cycloaddition.3•5-7 In an attempt to describe the electronic mechanism involved in the photocycloaddition of skin-sensitizing compounds to DNA bases, we have previously studied the excited states of coumarin as a model skin sensitizer.7 8 The present paper summarizes more complete studies, many at high resolution, of the excited states of a series of coumarins and psoralens.By far the most interesting molecule examined in this study is coumarylpyrone, benzo[ 1,2-6:4,5-6 'jdipyran-2,8-dione. The impetus for considering this particular system (and its analog benzo[l,2-6:4,5-6'Jdipyran-2,7-dione, which is yet to be synthesized) arose out of a previous work7 concerned with the photocycloaddition of the excited coumarins to DNA bases. In this work it was suggested that the triplet state of coumarin and its derivatives undergoes cycloaddition (at the 3,4 double bond) with pyrimidine bases of DNA. Two such double bonds within the molecular framework as found in coumarylpyrone would theoretically provide two active sites with an opportunity to crosslink both strands of the DNA double helix. Figure 1 shows the structures and numbering systems for coumarin, psoralen, isopsoralen, and coumarylpyrone.

Excited States of Biomolecules—iv

“…The spin density at the C=C group of the pyrone in the coumarin triplet is about 0.5, which is lower than the M O values calculated by Song and Gordon [132] but still in good agreement. The location of TI (n, a*) and S, (n, n*) with its nearby (n, n*) is in good agreement with Mantulin and Song [86].…”

Warfarin: an environment‐dependent switchable molecular probe

“…Although coumarin itself provides a fairly low fluorescence quantum yield at room temperature in most organic solvents (Song and Gordon, 1970;Lakowicz, 1999), the presence of different electron withdrawing or accepting substituents on the coumarin core structure can greatly influence the fluorescence properties (Mantulin and Song, 1973;de Melo et al, 1994;Reichardt, 1994;Gao et al, 2000;de Melo and Fernandes, 2001;Ammar et al, 2003;Sharma et al, 2003). The nature and position of substituents is important for the fluorescence behaviour of these compounds, and many spectroscopic and theoretical studies have been undertaken to characterize the photophysical behaviour of these substances (Machado et al, 2001(Machado et al, , 2003Ionescu and Hillebrand, 2003).…”

Optopharmacological control of TRPC channels by coumarin-caged lipids is associated with a phototoxic membrane effect

“…Psoralen, a naturally occurring coumarin derivative had been successfully used for clinical treatment of dermatological disorders (Mantulin and Song, 1973). It has been shown that psoralen can photoreact with unsaturated lipids and with molecular oxygen to produce active oxygen species such as superoxide and singlet oxygen that can cause damage to cell membrane (Park et al, 1996).…”