Search

[EN] Heteroarene boronate esters constitute valuable intermediates in modern organic synthesis. As building blocks, they can be further applied to the synthesis of new materials, since they can be easily transformed into any other functional group. Efforts toward novel and efficient strategies for their preparation are clearly desirable. Here, we have achieved the borylation of commercially available heteroarene halides under very mild conditions in an easy-to-use gel nanoreactor. Its use of visible light as the energy source at room temperature in photocatalyst-free and aerobic conditions makes this protocol very attractive. The gel network provides an adequate stabilizing microenvironment to support wide substrate scope, including furan, thiophene, selenophene, and pyrrole boronate esters., Financial support from the Generalitat Valenciana (CIDEGENT/2018/044) and the Spanish Ministry of Science and Innovation (PID2019-105391GB-C21, PID2019-105391GBC22, BEAGAL18/00166, and BES-2017-080215) is gratefully acknowledged. We thank the Electron Microscopy Service from the UPV and Prof. Julia Perez-Prieto for spectroscopy facilities. D.D.D. also thanks NANOtec, INTech, Cabildo de Tenerife, and ULL for laboratory facilities.

We have witnessed during the last decade the great evolution that visible-light photoredox catalysis has experienced as a powerful tool in organic synthesis and formation of new compounds can be now tackle. In this context, generation of radical intermediates such as aryl radicals and their subsequent trapping by the appropriate nucleophile is nowadays one of the main strategies to obtain added-value products.[1] The use of milder conditions and sometimes metal-free photocatalysts encompasses this methodology into the green principles from an economical and environmental point of view. Aryl phosphonates and their derivatives are fascinating moieties which present a widespread applicability in scientific fields such as life science, materials or as ligand in catalysis.[2] On the other hand, organoboron compounds, environmentally benign scaffolds, attract considerable interest not only in organic synthesis (they can be easily transformed into any other functional group) but also in other scientific areas of research, for example, as conjugated materials such as organic electronic applications and LEDs manufacturing or antimicrobial agents in medicinal chemistry.[3] Therefore, exploration of new procedures for their construction under milder conditions appears to be a challenge task. The question then arises whether production of new forming C(sp2) heteroatom (B, P) bonds can be achieved by visible light as energy source. Herein, we wish to show our recent results on the phosphorylation and borylation of five-membered heteroarene halides (Figure).[4] Regarding heteroarene phosphonates, a consecutive photoinduced electron transfer mechanism has been employed whereas new boronic esters have synthesized following a photocatalyst-free protocol. Interestingly, an easy-to-use gel nanoreactor has been used in both strategies which has permitted to enhance the production rate and to protect against oxygen poisoning.

The singlet excited state of 4-nitroquinoline N-oxide ( NQNO*) has been characterized by different spectroscopic techniques, combining transient absorption with steady state and time-resolved emission spectroscopy. The energy of NQNO* has been established as 255 kJ/mol from the fluorescence spectrum, whereas its lifetime has been found to be 10 ps in the femto-laser flash photolysis (LFP) experiments, where a characteristic S –S absorption band with maximum centered at 425 nm is observed. In a first stage, the triplet excited state of NQNO ( NQNO*) has also been characterized by emission spectroscopy in solid matrix, at low temperature. Thus, from the steady-state phosphorescence spectrum the triplet energy has been estimated as 183 kJ/mol, whereas the setup with time resolution has allowed us to determine the phosphorescence lifetime as 3 ms. Formation of NQNO* by intersystem crossing in solution at room temperature, has been monitored by femto-LFP, which shows the appearance of a band with maximum at 560 nm (T -T ). It increases with the decreasing intensity of its precursor 425 nm (S –S ) band, giving rise to an isosbestic point at 500 nm. The characterization of NQNO* has been completed by nano-LFP, using xanthone as photosensitizer and oxygen as well as β-carotene as quenchers. In addition, quenching of NQNO* by electron donors (DABCO) is also observed in aprotic solvents, leading to the radical anion of NQNO ([rad] NQNO). If there is a proton source in the medium (Et N as electron donor or MeCN:H O/4:1 as solvent system) protonation of the radical anion results in formation of the neutral radical of NQNO ([rad]NQNOH). In general, all processes are slower in protic solvents because of the solvation sphere. Overall, this information provides a deeper insight into the formation and behavior of excited states and radical ionic species derived from the title molecule NQNO., The work was financially supported by the Regional Government of Generalitat Valenciana (PROMETEO/2017/075) as well as the Spanish Government Science Department with the CTQ-2016-78875-P and CTQ-2009-13699 projects and the N. D.-G. fellowship (BES-2010-035875). BC, CC and FE acknowledge MIUR and the University of Perugia for financial support to the project AMIS, through the program “Dipartimenti di Eccellenza – 2018–2022”.

Solar filters, as photostable compounds, are used to protect the human skin against harmful UV radiation. Up until recently, sun protection was limited to the use of sunscreens whose active ingredients are UV filters, which reflect or absorb UV rays depending on their chemical nature. Today there is a trend toward higher sun protection factors and the use of additional ingredients in sunscreens aimed at further protecting against the indirect damage primarily caused by the deeply penetrating UVA rays. In fact, these wavelengths have been shown to generate reactive oxygen species, which become mediators of cellular oxidative damage, leading to oxidative stress and immune suppression in skin.

Photolysis of the title dyads under aerobic conditions leads to a 2-deoxyribonolactone derivative. Laser flash photolysis reveals that the process occurs from the short-lived benzophenone-like triplet excited state. A mechanism involving intramolecular electron transfer with the purine bases (adenine, guanine, or 8-oxoadenine) as donors is proposed.

The photochemistry of N-hydroxypyridine-2(1H)-thione (NHPT), inserted as a photolabile modifier at the 6-position of 2′-deoxyguanosine or guanosine, has been evaluated. In particular, 6-[(1-oxidopyridin-2-yl)sulfanyl]- (1a) and 6-[(pyridin-2-yl)sulfanyl]-2′,6-dideoxyguanosine (2a), novel photolabile derivatives of the natural nucleosides, were synthesized and characterized. The observed photolysis products of 1a in organic solvents could only be rationalized by assuming a rapid equilibrium with the corresponding 6-[(2-thioxopyridin-1(2H)-yl)oxy] analogue 3a (Scheme 5). Transient spectroscopy of 1a indicated a strong triplet-excited state suitable for triplet triplet energy transfer or singlet-oxygen generation. The NHPT function was stable enough for (slightly modified) automated solid-phase oligonucleotide synthesis. The utility of the above compounds is discussed, as well as their potential use in photosensitization of reactive oxygen species in DNA.

Time-resolved and product studies on the synthesized dyads 1 and 2 have provided evidence that the benzophenone-to-thymine orientation strongly influences intramolecular photophysical and photochemical processes. The prevailing reaction mechanism has been established as a Paterno-Büchi cycloaddition to give oxetanes 3-6; however, the ability of benzophenone to achieve a formal hydrogen abstraction from the methyl group of thymidine has also been evidenced by the formation of photoproducts 7 and 8. These processes have been observed only in the case of the cisoid dyad 1. Adiabatic photochemical cycloreversion of the oxetane ring is achieved upon direct photolysis to give the starting dyad 1 in its excited triplet state. The photobiological implications of the above results are discussed with respect to benzophenone-photosensitized damage of thymidine.

Two thymidine-derived nucleosides 1 and 2 were prepared by attaching a chiral naphthalene to the positions 5′ and 3′ of the sugar. The resulting dyads, which contain key substructures present in drugs and nucleic acids, exhibit different spatial arrangements (transoid or cisoid) of the fluorophore relative to the thymine unit. Emission measurements on these compounds in the presence of ROH molecules revealed a remarkable intramolecular fluorescence quenching for dyad 1. The obtained results are consistent with quenching of the singlet excited state of 1 by hydrogen-bond donor solvents. Thus, a physical deactivation process (vibronically induced internal conversion) would be the pathway responsible for the accelerated decay of 1*, favorably competing with fluorescence and intersystem crossing to the triplet. This effect appears to be strongly dependent on the relative spatial arrangement between the naphthalene and thymine units, together with the hydrogen-bonding ability of the employed ROH.

The detailed triplet state characteristics of 2-(4-acetylphenyl)isoindolin-1-one (kINP), a N-phenylphthalimidine (PPI) derivative, have been studied in fluid solution at room temperature. The attac...

Time-resolved and product studies have shown that there is a strong interaction between drugs containing the benzophenone chromophore and the free thymidine nucleoside. In quantitative terms, such an interaction is stronger for the lowest lying npi* triplet states (S-ketoprofen) than for mixed npi*-pipi* triplets (fenofibrate and fenofibric acid), as indicated by the quenching rate constants. This is consistent with a Paterno-Büchi photoreaction, where the initial step is the formation of a new bond between the excited carbonyl oxygen and one of the thymine olefinic carbons. Actually, oxetanes are obtained as photoproducts when benzophenone is irradiated in the presence of thymidine. Hence, triplet-triplet energy transfer resulting in formation of cyclobutane pyrimidine dimers, which would be thermodynamically disfavored, does not seem to play a major role. However, in DNA, the contribution of energy transfer could be higher, due to the lower energy of the thymine triplet in the biomacromolecule. These results are discussed in connection with the observed DNA damage upon photosensitization with ketoprofen, fenofibrate, and fenofibric acid.

The electronic absorption spectra, luminescence spectra and lifetimes (in MeCN at room temperature and in frozen n-C3H7CN at 77 K), and electrochemical potentials (in MeCN) of the novel dinuclear [(tpy)Ru(3)Os(tpy)]4+ and trinuclear [(tpy)Ru(3)Os(3)Ru(tpy)]6- complexes (3 = 2,5-bis(2,2':6',2''-terpyridin-4-yl)thiophene) have been obtained and are compared with those of model mononuclear complexes and homometallic [(tpy)Ru(3)Ru(tpy)]4+, [(tpy)Os(3)Os(tpy)]4+ and [(tpy)Ru(3)Ru(3)Ru(tpy)]6+ Complexes. The bridging ligand 3 is nearly planar in the complexes, as seen from a preliminary X-ray determination of [(tpy)Ru(3)Ru(tpy)][PF6]4, and confers a high degree of rigidity upon the polynuclear species. The trinuclear species are rod-shaped with a distance of about 3 nm between the terminal metal centres. For the polynuclear complexes, the spectroscopic and electrochemical data are in accord with a significant intermetal interaction. All of the complexes are luminescent (phi in the range 10(-4)-10(-2) and tau in the range 6-340 ns, at room temperature), and ruthenium- or osmium-based luminescence properties can be identified. Due to the excited state properties of the various components and to the geometric and electronic properties of the bridge, Ru --> Os directional transfer of excitation energy takes place in the complexes [(tpy)Ru(3)Os(tpy)]4+ (end-to-end) and [(tpy)Ru(3)Os(3)Ru(tpy)]6+ (periphery-to-centre). With respect to the homometallic case, for [(tpy)Ru(3)Os(3)Ru(tpy)]6+ excitation trapping at the central position is accompanied by a fivefold enhancement of luminescence intensity.

Reaction of K4[Ru(CN)6] with 2,2′:4′,4″-terpyridine (L1) or 2,2′:3′,2″:6″,2‴-quaterpyridine (L2) in acidic aqueous methanol affords the complexes K2[Ru(L1)(CN)4] and K2[Ru(L2)(CN)4] respectively, both containing the {Ru(bipy)(CN)4}2− chromophore but with pendant pyridyl or bipyridyl units, respectively. Time-resolved IR analysis of K2[Ru(CN)4(L2)] in MeCN–D2O showed that the most intense CN stretching vibration shifted to higher energy by ca. 50 cm−1 after laser excitation, consistent with formation of a Ru(III)/(L2)˙− MLCT excited state for which the lifetime measurement (38 ± 5 ns, measured by TRIR) agrees reasonably well with the value measured by luminescence methods (30 ± 2 ns). Study of the pH dependence of the absorption and emission spectra of the two complexes revealed the presence of two different effects arising from protonation of the pendant pyridyl/bipyridyl site (which occurs with pKa ≊ 3.1 in each case) and protonation of the cyanide ligands (which occurs with pKa ≊ 2 in each case). For K2[Ru(L1)(CN)4], protonation of the pendant pyridyl unit results in the 1MLCT excited state being lowered in energy by ca. 1000 cm−1, whereas at lower pH values (2.5–1), protonation of the cyanide ligands raises the 1MLCT excited state energy by over 2000 cm−1. For K2[Ru(L2)(CN)4] in contrast, protonation of the pendant bipyridyl unit has no detectable effect on the 1MLCT energy, as the pendant site is electronically decoupled from the complex core by a substantial twist between the free and coordinated bipy components of L2; protonation of the cyanides at lower pH values however destabilises the 1MLCT excited state. Protonation of the pendant pyridyl sites results in complete (for [Ru(L1)(CN)4]2−) or near-complete (for [Ru(L2)(CN)4]2−) quenching of the luminescence; possible reasons for this behaviour are discussed. The crystal structures of the two related complexes [Ru(tBu2bipy)2(L1)][PF6]2 and [Cl2Pt(μ-L2)Ru(bipy)2][PF6]2 are also described to illustrate arguments about the conformations of L1 and L2.

A [2]-rotaxane Zn2−Au+ made from a dumbbell component ended by Zn(II) porphyrin stoppers and a ring component incorporating a Au(III) porphyrin has been assembled in 13% yield using the transition metal templating route. 1H NMR studies show that its conformation in solution is very different from those of its complexes with Cu+, Ag+, and Li+. In particular, removal of the templating metal resulted in a changeover of the molecule, the threaded macrocycle undergoing a pirouetting motion placing the Au(III) porphyrin in the cleft formed by the two Zn(II) porphyrin stoppers. At room temperature, the changeover could be either complete or partial, depending on the solvent used. Photoinduced electron transfer from one of the Zn(II) porphyrins to the Au(III) porphyrin of the macrocycle was evidenced in the case of the free rotaxane and its Cu(I) complex, Zn2Cu+Au+. In the former case, the photoinduced electron transfer process could be clearly resolved for an extended conformation that is characterized by the Zn...

30 years of IrIII coordination chemistry with polyimine-type ligands are summarized. Over the years, milder reaction conditions have been used for their synthesis, allowing the incorporation of various functional substituents. Complexes are described with bidentate and terdentate ligands, with both N- and C-donor sites. All complexes are luminescent, with predominantly charge-transfer or ligand-centred emissive states depending on the charge density donated from the ligands to the metal. IrIII excited state lifetimes range from nanoseconds to microseconds. A wide range of properties are obtained: [IrN6]3+ complexes are strong photooxidants while tris-cyclometallated [IrN3C3] complexes are strong photoreductants.

The binuclear complex [{Ru(bipy)2}(μ-L1){Re(CO)3(H2O)}][PF6]3 (Ru-crw-Re), and its mononuclear counterpart [Ru(bipy)2(L1)][PF6]2, were synthesised. The bridging ligand L1 contains two bipyridyl binding sites which are attached via methylene spacers to each of the N atoms of a diaza-18-crown-6 macrocycle spacer (crw), such that addition of a metal ion to the macrocycle affects the pathway linking the two chromophores. The absorption spectra, luminescence spectra and excited-state lifetimes, and electrochemical properties of acetonitrile solutions of these complexes were investigated. Luminescence studies on Ru-crw-Re showed the presence of two competing types of photoinduced intramolecular process involving the Re-based excited state as a donor, viz.: (i) electron transfer from an amine group(s) of the aza-crown ether; and (ii) Re→Ru energy transfer. These processes were monitored by time-resolved luminescence spectroscopy both at room temperature and at 77 K, and in the presence and absence of a cation (Ba2+) hosted within the aza-crown macrocyclic unit. In fluid solution at room temperature, there is no photoinduced Re→Ru energy transfer; instead photoinduced electron transfer occurs in the absence of Ba2+ (kel = 1.2 × 1010 s−1), which is inhibited by the presence of Ba2+. In frozen solvent (77 K), only Re→Ru photoinduced energy transfer occurs, with ken = 2 × 108 s−1 in the absence of Ba2+ and kenBa = 7 × 106 s−1 in the presence of Ba2+. Thus, Re→Ru energy transfer is strongly affected by Ba2+ being hosted within the aza-crown cavity, i.e. a switching effect. The role of the diverse factors affecting the two processes is discussed in detail.

Carprofen (1a) is a photosensitizing nonsteroidal anti-inflammatory drug. It undergoes photodehalogenation from its triplet excited state. The resulting aryl radical (II) is able to abstract hydrogen atoms from model lipids, mediating their peroxidation by a type I mechanism. This aryl radical intermediate appears to be responsible for the observed photobiological effects of carprofen. The active involvement of the triplet state has been confirmed by direct detection of this species in laser flash photolysis and by quenching experiments with cyclohexadiene and naphthalene. Carprofen also photosensitizes singlet oxygen production with a quantum yield of 0.32. A minor reaction pathway is photodecarboxylation, which occurs from the excited singlet state and leads to an acetyl derivative (1b). In the case of the dehalogenated photoproduct (2a), photodecarboxylation to the ethyl (2d) and acetyl (2b) derivatives, together with singlet oxygen production (quantum yield = 0.18), is also possible. However, the biological activity of 2a in the linoleic acid photoperoxidation and photohemolysis tests is markedly lower than that of 1a, which constitutes further evidence in favor of the important role of photodehalogenation in the adverse photobiological effects of carprofen.

One-electron oxidized guanine is an important reactive intermediate in the formation of oxidatively generated damage in DNA and a variety of methods have been utilized for the abstraction of a single electron from the guanine moiety. In this study, an alternative approach for the site specific, independent generation of the guanine radical, utilizing N-hydroxypyrid-2(1H)-one as a photolabile modifier of guanine, is proposed. Novel photolabile 6-[(1-oxido-2-pyridinyl)oxo]-6-deoxy- and 2′,6-dideoxy-guanosine derivatives capable of generating the neutral guanine radical (G(-H)˙) upon photolysis were synthesized and characterized. The generation of G(-H)˙ proceeds through homolysis of the N–O bond and was confirmed through continuous photolysis product analysis and trapping studies, as well as laser flash photolysis experiments.

One-electron oxidized guanine is an important reactive intermediate in the formation of oxidatively generated damage in DNA and a variety of methods have been utilized for the abstraction of a single electron from the guanine moiety. In this study, an alternative approach for the site specific, independent generation of the guanine radical, utilizing N-hydroxypyrid-2(1H)-one as a photolabile modifier of guanine, is proposed. Novel photolabile 6-[(1-oxido-2-pyridinyl)oxo]-6-deoxy- and 2′,6-dideoxy-guanosine derivatives capable of generating the neutral guanine radical (G(-H) •) upon photolysis were synthesized and characterized. The generation of G(-H) proceeds through homolysis of the N-O bond and was confirmed through continuous photolysis product analysis and trapping studies, as well as laser flash photolysis experiments. {\textcopyright} The Royal Society of Chemistry 2009.

Under sunlight irradiation (5′S)-5′,8-cyclo-2′-deoxyadenosine 2 photoisomerises to the (5′R) isomer 1, which is the more easily repaired damage when these cyclopurine lesions are formed in DNA.

The photochemistry of N-hydroxypyridine-2(1H)-thione (NHPT), inserted as a photolabile modifier at the 6-position of 2′-deoxyguanosine or guanosine, has been evaluated. In particular, 6-[(1-oxidopyridin-2-yl)sulfanyl]- (1a) and 6-[(pyridin-2-yl)sulfanyl]-2′,6-dideoxyguanosine (2a), novel photolabile derivatives of the natural nucleosides, were synthesized and characterized. The observed photolysis products of 1a in organic solvents could only be rationalized by assuming a rapid equilibrium with the corresponding 6-[(2-thioxopyridin-1(2H)-yl)oxy] analogue 3a (Scheme 5). Transient spectroscopy of 1a indicated a strong triplet-excited state suitable for triplet → triplet energy transfer or singlet-oxygen generation. The NHPT function was stable enough for (slightly modified) automated solid-phase oligonucleotide synthesis. The utility of the above compounds is discussed, as well as their potential use in photosensitization of reactive oxygen species in DNA. {\textcopyright} 2006 Verlag Helvetica Chimica Acta AG.

Time-resolved measurements using nanosecond laser flash photolysis have revealed significant enantiodifferentiation in the interaction between ketoprofen (a chiral benzophenone derivative) and two relevant nucleosides, namely, thymidine and 2‘-deoxyguanosine. In both cases, the highest quenching rate constants have been observed for (R)-ketoprofen, the enantiomer with lower pharmacological activity. Photoproduct studies performed in the case of thymidine suggest that the enantiodifferentiating process corresponds to a Paterno−Buchi reaction, leading to the formation of oxetanes. With 2‘-deoxyguanosine, the quenching is associated with an electron-transfer process monitored through the generation of a ketyl radical.

30 years of IrIII coordination chemistry with polyimine-type ligands are summarized. Over the years, milder reaction conditions have been used for their synthesis, allowing the incorporation of various functional substituents. Complexes are described with bidentate and terdentate ligands, with both N- and C-donor sites. All complexes are luminescent, with predominantly charge-transfer or ligand-centred emissive states depending on the charge density donated from the ligands to the metal. IrIII excited state lifetimes range from nanoseconds to microseconds. A wide range of properties are obtained: [IrN6]3+ complexes are strong photooxidants while tris-cyclometallated [IrN3C3] complexes are strong photoreductants.

For a diruthenium complex, charge migration between different moieties of a bridging ligand with extended conjugation is directly monitored for the first time by using time-resolved emission and absorption spectroscopy.

Diclofenac (1) is a photosensitizing nonsteroidal antiinflammatory drug. Its photodecomposition gives rise to chlorocarbazole 2a. This product undergoes photodehalogenation to 3a in a subsequent step. When the photobiological activities of 1, 2a, and 3a are compared by means of the photohemolysis test, it is clearly observed that chlorocarbazole 2a causes cell lysis with a markedly higher efficiency than the parent drug or the secondary photoproduct 3a. Laser flash photolysis studies suggest that photodehalogenation of 2a occurs from its excited triplet state via quenching by ground-state 2a and formation of an excimer. As a consequence, an aryl radical plus an N-centered carbazolyl radical are formed. These radical intermediates appear to be responsible for the observed photobiological effects of diclofenac, via hydrogen abstraction from the target biomolecules, which initiates a type-I photodynamic effect. The efficient peroxidation of model lipids, such as linoleic acid, photosensitized by 2a are in favor of this proposal. Thus, the photosensitizing properties of diclofenac appear to be associated with the photochemical and photobiological activity of its major photoproduct.

Using two diastereomeric dyads containing naphthalene and thymine units, significant chiral discrimination has been found in the photophysical processes involving the naphthalene excited states: singlet deactivation by hydrogen bonding molecules, singlet-singlet energy transfer from thymine and triplet decay.

The photophysical properties and photochemistry of indoprofen (INP) have been investigated. Absorption and emission spectroscopies in phosphate buffer, ethanol and ether show that INP photophysics is dominated by a singlet-singlet transition of pipi* character. INP fluoresces at room temperature, with a quantum yield approximately 0.04. Flash photolysis experiments together with the lack of phosphorescence at room temperature point to a very weak intersystem crossing. The photoreactivity of INP is centered on the propionic acid chain and gives rise to photoproducts similar to those obtained with other arylpropionic acids (ethyl, hydroxyethyl and acetyl derivatives). Thus, irradiation of INP in aqueous buffer results in photodecarboxylation and leads mainly to oxidative compounds whose proportions increase with increasing oxygen concentration. These data suggest a photoreactivity occurring from the excited singlet state.

The effect of β-cyclodextrin (β-CD) on the excited-state reactivity of the two benzoylthiophene derivatives, tiaprofenic acid (TPA; 2) and suprofen (SPF; 3) in their carboxylate forms is studied. The presence of β-cyclodextrin does not affect the nature of the photoproduced transients and the photoproducts, but increases the photodegradation quantum yields of both drugs. The efficiency of the photodecarboxylation process is enhanced. This effect is rationalized in the light of the inclusion of 2 and 3 in the β-CD cavity, affecting the energy of the lowest excited states of the drugs. The structure of the complexes is determined by induced circular dichroism, and molecular-mechanics and dynamic Monte Carlo calculations. The photoreactivity of the decarboxylated photoproduct 7 of tiaprofenic acid (2) in presence of β-CD is also examined.

— The photoreactivity of the photosensitizing nonsteroidal anti-inflammatory drug tiaprofenic acid (TA) and its photoproduct decarboxytiaprofenic acid (DTA) was studied both in the presence and in the absence of bovine serum albumin (BSA). The photoproduct DTA was found to be photostable in buffered aqueous solution at pH 7.4, but photodecomposed when BSA was present in the reaction medium. Both TA and DTA underwent irreversible photobinding to BSA in an almost quantitative way, as evidenced by radioactivity measurements using labeled (3H) compounds. In the case of TA, it has been proven that photobinding is mainly attributable to the phototoreactivity of in situ -generated DTA. The photo-degradation and photobinding of TA were also investigated in the epidermis in vivo. Rats were exposed to UVA after application of TA to their shaven dorsal skin. During the initial periods of irradiation, the amount of TA decreased sharply, and the yield of the corresponding photoproduct (DTA) reached a maximum. Prolonged irradiation led to photodegradation of DTA. In vivo photobinding was studied using 3H-TA. Photobinding took place slowly at the beginning, but its rate increased sharply after complete photoconversion of TA, when the photoproduct DTA reached the maximum concentration. Thereafter, the decrease of DTA was more pronounced than that of TA. This indicates thatalso in vivoDTA rather than TA is responsible for the photobinding to biomacromolecules in the viable layer of the epidermis. Overall, the above results suggest that irradiation of TA in buffered aqueous solution, in the presence of proteins, is a reasonable model system to study the photodegradation and photobinding behavior of this drug in vivo. From the qualitative point of view, the main conclusion is that DTA plays a key role both in vivo and in vitro: it is the major photoproduct, it undergoes further photodegradation upon prolonged irradiation, and it appears to be responsible for the photobinding process.

Photoexcitation of tiaprofenic acid (TPA) in aqueous medium leads with almost unitary efficiency to the lowest π,π* triplet, which is detected by transient absorption. The deactivation of this state occurs in the microsecond time domain and is dominated by a thermally activated spin-allowed process with –10 kcal/mol energy barrier. The occurrence of decarboxylation from an upper state, likely the second triplet of n, π* character, is confirmed by the study of the transients toward the final keto photoproduct, i.e. the benzoylthiophene ethyl derivative (DTPA). At neutral pH, upon adiabatic release of the CO2 fragment, long-lived triplet biradicals and ground-state intermediates with a protonated carbonyl oxygen are formed. Laser flash photolysis of DTPA leads almost quantitatively to the lowest π,π* triplet, with similar T-T absorption features as those of TPA. However the DTPA triplet appears essentially unreactive in aqueous medium. In isopropanol H-abstraction from the solvent is demonstrated by the formation of the ketyl radical.

The 2-benzoylthiophene chromophore of the photosensitizing drug tiaprofenic acid and of its decarboxylated derivative is characterized by a unusually high energy gap between the T1 (pi, pi*) and T2 (n, pi*) excited states, which makes this a unique system to study the intrinsic photoreactivity of the two states. Weak fluorescence and phosporescence emission were detected at room temperature. Tiaprofenic acid undergoes photodecarboxylation from the triplet manifold as the main reaction. The photoprocess is temperature dependent with activation energy of 7-10 kcal/mol, close to the energy gap between T1 and T2. The decarboxylated product abstracts hydrogen in type I reactions. The involvement of T2 in the above processes is proposed. Moreover the decarboxylated derivative exhibits reactivity toward phenols, consistent with a participation of the T1 state as electron acceptor. The observed photoprocesses can account for biological photosensitization reactions, like membrane damage and protein modification.

Diclofenac and meclofenamic acid are two structurally related nonsteroidal anti-inflammatory drugs with some photosensitizing potential. Their photochemistry involves cyclization to monohalogenated carbazoles. In principle, photocyclization could occur by photodehalogenation, followed by intramolecular radical addition, or by 6TT electrocyclization and subsequent dehydrohalogenation of the intermediate dihydrocarbazoles. Previously, it has been assumed that the reaction follows the first pathway and that the key species associated with phototoxicity are the resulting aryl radicals. In the present work, we have performed photophysical and photochemical studies on 2,6-dichlorodiphenylamine (la). This is a suitable model compound because since it contains the active chromo-phore present in diclofenac and meclofenamic acid, and its photoreactivity should be relevant to the understanding of the photobiological properties of both drugs. Our results clearly show that the first photochemical reaction is a very rapid 6iT-electrocyclization, and hence no radicals are formed at this stage. Instead, cleavage of the carbon-halogen bond occurs in the 1-chlorocarbazole photoproduct 2a. The reduced lifetime of the 2a triplet (as compared with the unsubstituted carbazole) and the observed reaction quenching by oxygen are in agreement with the reaction occurring from the excited triplet state. Overall, the above results suggest that the potential phototoxicity of diclofenac and meclofenamic acid is due to a photobiologically active photoproduct that is able to generate radicals upon photolysis, rather than to the parent drug.

Solvent-dependent conformational changes of a poly(oxoethylene) bridge linking [Ru(bipy)3]2+ and [Os(bipy)3]2+ units can be probed by measuring the extent of Ru→Os photoinduced energy transfer.

Whereas {Ru(terpy)2}2+ salts are essentially non-luminescent in fluid solution luminescent molecular wires with {Ru(bpy)3}2+-like activity result when these units are connected by 2,5-thiophenediyl spacers.

In a dinuclear complex containing both [ReCl(CO)3(bpy)] and [Ru(bpy)3]2+ chromophores, the bis(bipyridylethenyl)- benzene bridge acts as an intermediate reservoir of energy for two-step Re→Ru photoinduced energy transfer.