STUDIES ON THE PHOTOTOXICITY OF COUMARIN DERIVATIVES — I. PHOTOCYCLODIMERIZATION OF 5,7-DIMETHOXYCOUMARIN

Abstract— 5,7-DimethoxJtcoumarin (DMC) dimerizes through the C₄-photo-cycloaddition of 3,4-double bonds to form a syn head-to-tail dimer on direct irradiation ( Λ≥ 300 nm) in acetonitrile or benzene solution. The quantum yield of the photocyclodimerization in acetonitrile is 0.068 which is greater than that of coumarin.
In the presence of triplet sensitizers such as benzophenone, 5,7-dimethoxycoumarin forms an anti dimer with the quantum yield greater than 0.08. The structure of the photodimers has been elucidated by IR, UV, NMR, and mass spectrometry. The results of luminescence studies, triplet quenching and sensitization revealed that the syn head-to-tail dimer was formed via an excited singlet precursor, while the anti dimer was formed via the excited triplet state.     

TRIPLET ELECTRONIC STRUCTURE AND PHOTOREACTIVITY OF 8-METHOXYPSORALEN*

Psoralen and its derivatives are implicated in a variety of photobiological processes including skin-sensitization in mammals, the experimental photochemotherapy of psoriasis, and photomutagenesis in bacteria. Although the various derivatives differ markedly in photoactivity, their excited triplet states as characterized by conventional luminescence spectroscopy are very similar and closely resemble that of the parent compound, coumarin, which is inactive as a skin sensitizer. Employing a more sensitive probe of triplet electronic structure, we have utilized optical detection of magnetic resonance to measure the zero-field splittings in the triplet state of several psoralens and find a striking variation among the derivatives. D*, taken as a composite measure of the dipole-dipole interaction of the unpaired electrons in the triplet state was found to be anomalously large, greater than 0.140 cm^-1, for the very active compounds, psoralen and 8-methoxypsoralen, while D*= 0.124cm^-1 for the inactive, though smaller, coumarin molecule. Although 8-hydroxypsoralen has a large D* value its inactivity as a skin-sensitizer may be explained by the dissociation of the hydroxyl proton. The resulting (excited) triplet state anion has D*= 0.120 cm^-1.     

A THEORETICAL TREATMENT OF THE ELECTRONIC STATES OF THIONINE AND RELATED MOLECULES

Abstract— –Problems associated with the protolytic equilibria of thionine and related molecules in their lowest excited electronic states were investigated. The theoretical arguments are based on semi-empirical SCF MO (CI) calculations for the π-electronic system of these molecules; all singly excited configurations were included in the CI. The results indicate that the basic form of thionine in its ground, first excited singlet and lowest triplet state is protonated at the heterocyclic N atom. The difference of the p K values of these three states can be explained in terms of the calculated charge densities. The photochemical reactivity of the lowest triplet of the acidic form of thionine (³TH₂²⁺) differs greatly from that of the lowest triplet of the basic form (³TH⁺). Some arguments for the assignment of nπ* character to ³TH₂²⁺ and ππ* character to ³TH⁺ are advanced.     

Chemically Initiated Electron Exchange Luminescence of Silyloxyaryl-Substituted Spiroadamantyl Dioxetanes: Kinetics and Excited State Yields

Abstract— The kinetics of the fluoride-induced decomposition of the thermally stable silyloxyaryl-substituted spiroadamantyl dioxetanes 1a,b and the excited state formation of this chemically initiated electron exchange luminescence (CIEEL) have been investigated. Two limiting kinetic regimes flash and glow have been identified, which depend on the fluoride concentration, the first at high, the second at low [F^-] triggering, whose detailed kinetic analysis affords the rate constants for the deprotected dioxetanes 2a,b cleavage in acetonitrile and dimethyl sulfoxide and chemiluminescence measurements the CIEEL and phen-olate 4 (CIEEL emitter) excitation yields. Chloro-substi-tution in the spiroadamantyl dioxetane does not affect the deprotection step k ₂ but leads to a ca five-fold faster cleavage of the deprotected dioxetane 2, while the chemiexcitation yield is the same for both dioxetanes. The energies of the first excited singlet and triplet states of the emitting phenolate 4 were estimated by AM1 configuration interaction calculations with explicit consideration of acetonitrile as solvent (self-consistent reaction field approach). The first excited singlet and triplet state of the CIEEL emitter phenolate 4 possess π,π* character, as suggested by the π-type molecular orbitals and the large singlet-triplet energy gap. The chemiexcitation of both singlet and triplet states of the excited phenolate 4 is feasible during the dioxetanes 1a,b cleavage, but the experimentally determined high singlet excitation yields suggest that preferentially the phenolate 4 singlet state is populated in the fluoride ion-triggered CIEEL process.     

8-甲氧基呋喃并[3',2':6,7]香豆素与烯烃光环合加成反应的研究I.

The photocycloaddition of 8-methoxypsoralen to cyclothexene and to heptene-1 was found to give 3,4-dihydrobicyclo (4,2,0) octano (7",8":3,4) 8-methoxypsoralen (4) and a mixture of 3, 4-dihydro-(1-n-pentyl) cyclobutano-(2", 3":3,4) 8-methoxypsoralen (5) and the isomer 6 respectively. Stern-Volmer plot and quenching studies indicate that the reaction proceeds via psoralen triplet excited state.     

CORRELATION BETWEEN THE TRIPLET PHOTOPHYSICAL PROPERTIES AND THE PHOTOBIOLOGICAL ACTION IN YEAST OF TWO MONOFUNCTIONAL PYRIDOPSORALENS

The photophysical properties of the lowest excited triplet states of pyrido[3,4-c]psoralen (PyPs) and 7-methylpyrido[3,4-c]psoralen (MePyPs) have been investigated by laser flash photolysis, including energy transfer from these triplets to oxygen-generating singlet oxygen. A parallel study of the photosensitization of yeast in vivo by these compounds in the presence and absence of oxygen is also reported. The low triplet and hence singlet oxygen yields, reflected in the lack of an oxygen effect in yeast, suggest that photoadditions to DNA are likely to be the main source of the photosensitized lethal effects induced by these pyridopsoralens in vivo.     

Photosolvolysis of 3,4-dichloroaniline in water : Evidence for an aryl cation intermediate

Irradiation of 3,4-dichloroaniline in water (λ > 290nm) gave 2-chloro-5-aminophenol with a conversion of 78±5%. The photolysis quantum yield at 313 nm of 0.052±0.003 was unaffected by cyanide (0.35 M) or pH changes between 4 and 12. A MO calculation indicated a large excited singlet state shift in electron density to the carbon undergoing substitution. The reaction is suggested to proceed through an aryl cation intermediate produced by heterolytic cleavage of the meta carbon-chlorine bond. Reaction from the triplet state is not considered likely since neither oxygen nor sorbic alcohol affected the quantum yield.     

EXCITED STATES AND REACTIVITY OF CARCINOGENIC BENZPYRENE; A COMPARISON WITH SKIN-SENSITIZING COUMARINS*

Abstract— Significant spectroscopic difference was found between the ³(π, π*) state of coumarins and the ³L_a state of benzpyrene. No analogy of the partially localized triplet state associated with the coumarin chromophore was revealed in the case of the potent carcinogen, benzo[a]pyrene. Instead, the ³L_a state of benzo[a]pyrene is characterized by more derealization than that of the non–carcinogenic benzo[e]pyrene. Therefore, the predominant photoreaction between benzo[a]pyrene and DNA bases does not seem to involve cycloaddition in contrast to the coumarin-pyrimidine system. Reactivity indices have been calculated, and results are consistent with recent experimental findings. In addition, spectroscopic properties of benzo[a]pyrene and benzo[e]pyrene have been comparatively described in terms of relatively high-resolution spectra, polarization measurements, and molecular orbital calculations.     

Photoreactivity of furocoumarins and DNA in PUVA therapy: formation of psoralen-thymine adducts

The mechanism of the [2+2] cycloaddition photoreaction of psoralen and a DNA nucleobase, thymine, cornerstone of the furocoumarin-based PUVA (psoralen+UVA radiation) phototherapy, has been studied by the quantum-chemical multiconfigurational CASPT2 method. Triplet- and singlet-mediated mono- and diadduct formations have been determined to take place via singlet-triplet crossings and conical intersections, correlated with the initially promoted triplet or singlet states in different possible reactive orientations. Pyrone-side monoadducts are suggested to be formed in the triplet manifold of the system, and to be less prone to yield diadducts because of the properties of the monoadduct lowest triplet state and the minor accessibility of its excited singlet states. Furan-side monoadducts are better produced in the singlet manifold after reaching a conical intersection with the ground state of the system. From there, the absorption of a second photon would in this case trigger the formation of the diadduct. The proposed mechanisms enable rationalizing the phototherapeutic behavior of several furocoumarins.     

265 NM LASER FLASH PHOTOLYSIS OF SOME ORTHO-SUBSTITUTED ANILIDES AND RELATED N-FORMYLKYNURENINE DERIVATIVES

Abstract— The physical and chemical properties of the triplet state of eight ortho-substituted anilides including N -formylkynurenine (FK), the major trp UV-photooxidation product and a remarkable photodynamic agent, have been investigated using both pulse radiolysis and 265 nm laser flash photolysis techniques. The molar extinction coefficient, the intersystem-crossing quantum yield and the oscillator strength of the T ₁→ T _n absorption band (Λ_max˜ 450 nm) have been determined. It is shown that anilides having n,π* triplets readily react with most solvents whereas those having π ,π* triplets slowly react with alcohols. In both cases, the semi-reduced species are formed. In water, the formation of the semi-reduced. species most probably involves the first excited singlet state. The triplet state properties of the FK derivatives (i.e. ortho-substituted anilides having a side chain bearing charged groups such as carboxylic or amino groups) are strongly modified by the ionization state of the charged side chain. In the case of the FK derivatives possessing an uncharged amino group, quenching of the triplet state occurs via a fast reversible electron transfer reaction from the NH₂ to the triplet anilide.     

A new-type photoreaction of a carbonyl compound: Part 2. Photoinduced ω-bond dissociation in p-halomethylbenzophenone studied by time-resolved EPR technique and laser flash photolysis

Photodissociation of the carbon-X (X = Br and Cl) bonds in p-bromo- and p-chloromethylbenzophenone (BMBP and CMBP) in solution were investigated by time-resolved EPR and laser flash photolysis techniques. BMBP and CMBP were found to undergo ω-bond cleavage to yield the p-benzoylbenzyl radical (BBR) at 295 K, and the quantum yields (Φ_BBR) were determined. The CIDEP signal originated from BBR formed upon decomposition of CMBP was obtained while that for BMBP was absent. By using triplet sensitization of acetone, the efficiencies (_BBR) of the CX bond fission in the triplet states of BMBP and CMBP were determined. The agreement between the Φ_BBR and _BBR values for CMBP indicates that the CCl bond dissociation occurs only in the triplet state. In contrast to CMBP, the cleavage of the CBr bond in BMBP upon direct excitation was concluded to be the event only in the excited singlet state without triplet formation, whereas the triplet state was also reactive for ω-bond dissociation. The rate of CBr bond dissociation seemed to be greater than that of intersystem crossing from the S₁ to the T₁ state. Schematic energy diagrams of the excited states of BMBP and CMBP were shown, and the reaction profiles were discussed from the viewpoint of the CX bond enthalpies.     

Photopolymerization of 7,7′-coumarinyl polymethylene dicarboxylates: Fluorescence and kinetic study

All eight 7,7′-(4-methylcoumarinyl) polymethylene dicarboxylates (3, 4) containing terminal photoreactive coumarin chromophores show strong fluorescence intensities at room temperature in dimethyl sulfoxide (DMSO) and CH₂Cl₂. After irradiation with 350 nm light for 2 h, the fluorescence characteristics of the dicarboxylates reveal their photopolymerization paths. On irradiation of the unsubstituted dicarboxylates (3) in DMSO, singlet excited state excimers are formed, leading to syn head-to-head coumarin dimer configuration. However, for all dicarboxylates in CH₂Cl₂, the dimerization of the coumarin chromophore proceeds via a triplet excited state in the presence of benzophenone to form the anti-configuration photoproducts. Further confirmations of the reaction mechanism are made by kinetic studies. At high concentration, photopolymerization of 7,7′-(4-methylcoumarinyl) polymethylene dicarboxylate (4c) obeys zero-order and first-order kinetics for coumarin chromophore and benzophenone, respectively. This is a powerful proof of the proposed mechanism of a triplet excited state reaction. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2999–3008, 1997     

A SELF-CONSISTENT-FIELD STUDY OF THE EXCITED STATE π-ELECTRON CHARGES IN PHENOL

Abstract— –The semiempirical self-consistent-field (SCF) method was used to calculate the net π-electron charges for phenol in the first excited singlet and first excited triplet states. These calculations differ from the usual ground state calculations in that (i) recently available static excited state data were used wherever possible as the empirical basis for evaluating SCF parameters and (ii) the theory of density matrices was used to include the effects of all singly-excited configurations in the configuration interaction contributions to the excited state π-electron charge densities.     

The reactive state in the photo-rearrangement of o-nitrobenzaldehyde

The primayy step of the o-nitrobenzaldehyde-o-nitrosobenzoic acid photorearrangement in solution has been studied by flash absorption with 35 ps 355 nm light pulses. Flash photolysis of o-nitrobenzaldehyde in acetonitrile or THF solutions produces a transient absorption with a maximum at ca. 440 nm. Formation of the transient was < 35 ps, the laser pulse width, and within experimental error, no furthrr buildup was observed. The transient which decayed at nanosccond times is attributed to a remarkably reactive ketene intermediate formed by H abstraction of the aldehydic hydrogen by the excited state of the nitro group. Decay of the ketene was more rapid in water-acetonitrile, methanol-acetonitrile, tert-butyl alcohol and in THF than in acetonitrile solution. It is suggested that the intramolecular reaction of the ketene intermediate is enhanced in THF relative to acetonitrile because of the ability of THF to faciliaate proton transfer associated with the reaction. The addition of the triplet quencher cis-piperylene to a solution of o-nitrobenzaldehyde in THF did not accelerate decay of the transient nor reduce its yield. The n,π* triplet excited state band observed in the 625–650 nm region for a number of the nitroaromatic compounds was not observed in the case of o-nitrobenzaldehyde. The results provide evidence that in the direct irradiation on o-nitrobenzaldehyde in THF or acetonitrile solutions, the intramolecular reaction occurs from the singlet rather than the triplet excited state.     

Assignment of electronic transitions by geometry optimization

Adiabatic excitation energies, excited state geometries, excited state charges, bond orders and dipole moments have been obtained for HCN, CO₂,H₂CO, HFCO, F₂CO, ethylene, trans-butadiene, furan, pyrrole and uracil using the SINDO1 semi-empirical method with configuration interaction. Our results generally agree with those ofab initio calculations and experiment satisfactorily. Geometry optimization is found to mix configurations differing in their allowedness in vertical excitation from the ground state, which in turn helps in the assignment of spectral transitions. TheV excited singlet state of trans-butadiene and various excited states of furan, pyrrole and uracil have been found to be appreciably non-planar. The single and double CC bonds are found to exchange positions due to the lowest triplet and singlet transitions of furan and pyrrole. The first triplet and first singlet transitions of uracil have been found to be of π-π* and π-σ* types respectively in agreement with recent experimental findings. On leave of absence from the Department of Physics, Banaras Hindu University, Varanasi-221005, India     

A theoretical insight into the photophysics of psoralen

Psoralen photophysics has been studied on quantum chemistry grounds using the multiconfigurational second-order perturbation method CASPT2. Absorption and emission spectra of the system have been rationalized by computing the energies and properties of the low-lying singlet and triplet excited states. The S1 pipi* state has been determined to be responsible of the lowest absorption and fluorescence bands and to initially carry the population in the photophysical processes related to the phototherapeutic properties of psoralen derivatives. The low-lying T1 pipi* state is, on the other hand, protagonist of the phosphorescence, and its prevalent role in the reactivity of psoralen is suggested to be related to the elongation of the pyrone ring C3-C4 bond, where the spin density is distributed on both carbon atoms. Analysis of energy gaps and spin-orbit coupling elements indicates that the efficient photophysical process leading to the population of the lowest triplet state does not take place at the Franck-Condon region but along the S1 relaxation path.     

Coumarin 314 free radical cation: formation, properties, and reactivity toward phenolic antioxidants

We have explored the photogeneration of the coumarin 314 radical cation by using nanosecond laser excitation at wavelengths longer than 400 nm in benzene, acetonitrile, dichloromethane, and aqueous media. In addition, time-resolved absorption spectroscopy measurements allowed detection of the triplet excited state of coumarin 314 (C(314)) with a maximum absorption at 550 nm in benzene. The triplet excited state has a lifetime of 90 μs in benzene. It is readily quenched by oxygen (k(q) = 5.0 × 10(9) M(-1) s(-1)). From triplet-triplet energy transfer quenching experiments, it is shown that the energy of this triplet excited state is higher than 35 kcal/mol, in accord with the relatively large singlet oxygen quantum yield (Φ(Δ) = 0.25). However, in aqueous media, the coumarin triplet was no longer observed, and instead of that, a long-lived (160 μs in air-equilibrated solutions) free radical cation with a maximum absorbance at 370 nm was detected. The free radical cation generation, which has a quantum yield of 0.2, occurs by electron photoejection. Moreover, density functional theory (DFT) calculations indicate that at least 40% of the electronic density is placed on the nitrogen atom in aqueous media, which explains its lack of reactivity toward oxygen. On the other hand, rate constant values close to the diffusion rate limit in water (>10(9) M(-1) s(-1)) were found for the quenching of the C(314) free radical cation by phenolic antioxidants. The results have been interpreted by an electron-transfer reaction between the phenolic antioxidant and the radical cation where ion pair formation could be involved.     

Time-resolved EPR and laser photolysis investigations of photoinduced ω-bond dissociation in an aromatic carbonyl compound having triplet π,π* character

Photochemical properties of photoinduced ω-bond dissociation in p-phenylbenzoylbenzyl phenyl sulfide (PPS) having the lowest triplet state (T₁) of π,π* character in solution were investigated by time-resolved EPR and laser flash photolysis techniques. PPS was found to undergo photoinduced ω-bond cleavage in the excited lowest singlet state (S₁(n,π*)) with a quantum yield (Φ_rad) of 0.15 for the radical formation, which was independent of excitation wavelengths. Based on the facts of the observation of the absorption spectrum of triplet PPS upon triplet sensitization of xanthone, and absence of CIDEP signal, ω-cleavage was shown to be absent in the T₁(π,π*) state of PPS. Considering the electronic character of the excited and dissociative states of PPS, a schematic energy diagram for the ω-bond dissociation of PPS was shown.     

REVERSIBLE PHOTOCYCLOADDITION OF A 4',5'-DIHYDROPSORALEN DERIVATIVE WITH THYMINE

The photocycloaddition reaction between a 4′,5′-dihydropsoralen derivative and thymine was studied in solution using a synthetic bichromophoric model 8 in which the two rings are associated by a tetramethylene chain. In water this model molecule exhibits intramolecular ring-ring stacking interactions as evidenced by UV and NMR spectroscopies. Irradiation at 365 nm at usual concentrations ( 5.10^?-⁴M) leads exclusively to a regio- and stereo-selective dimerization reaction involving the 3,4 double bonds of the psoralen moities. Extreme dilutions (ca 2.10^?-⁵M) were necessary to observe the intramolecular reaction which results in the exclusive formation of a 3,4 cb-anti adduct. This reaction is completely reversed by irradiation at 254 nm. These results are discussed with regard to the behavior of the homologous models in which the furan part of the psoralen ring is not hydrogenated, These latter compounds also lead exclusively to a 3,4 cis-anti adduct. It appears that saturation of the furan ring increases strongly the quantum yield of the photaddition at 365 nm (0.01 → 0.18) and that the triplet excited state of the 4′,5′-dihydropsoralen is involved in the photoaddition.     

The photolysis of 3,4-dimethylcyclopentanone

The photolysis of trans-3,4-dimethylcyclopentanone has been studied in the gas phase, principally at 313 nm. However, a few experiments have also been performed using laser sources at 308 and 325 nm. Additionally, experiments were also carried out using the cis isomer. The major products produced by all three wavelengths and in the temperature range 100 to 150°C were propene, 1,2-dimethylcyclobutane, carbon monoxide, and 3,4-dimethylpent-4-en-al. The formation of the cyclobutane was stereospecific and the effects of temperature, pressure, and wavelength on the relative product yields could be rationalized in terms of a mechanism involving the formation of a vibrationally excited triplet state which could yield both hydrocarbons and the aldehyde and a nonexcited triplet yielding only the aldehyde. Some high intensity experiments with an exciplex laser at 308 nm gave results which could be due to the occurrence of some two photon absorption by the cyclopentanone or absorption by an excited intermediate. The results are compared with those previously reported for other substituted cyclopentanones.