Psoralen UV-A Therapy Research Articles

Nonsurgical Treatment of Postburn Hypopigmentation: A Literature Review.

The treatment of postburn hypopigmentation was primarily surgical before the advent of new technologies. Medical devices and therapies are emerging to manage scar sequelae that can be disfiguring and associated with severe psychosocial impact. These innovations have been poorly investigated for hypopigmentation, but they represent a real hope. We reviewed all articles published on Pubmed up to June 2022. Included studies had to specifically focus on treating postburn hypopigmented scars. All articles evaluating transient solutions such as make-up, and articles describing inflammation-linked hypopigmentation with no etiological details or no burn injury history were excluded. Through this review, we have highlighted 6 different types of nonsurgical treatments reported in postburn leukoderma potentially allowing definitive results. Electrophoto-biomodulation or E light (combining intensive pulsed light, radiofrequency, and cooling), topical daylight psoralen UVA therapy, and lasers (fractional lasers using pulse energies or CO2FL devices, lasers-assisted drug delivery as local bimatoprost and tretinoin or pimecrolimus) have been explored with encouraging results in hypopigmented burns. Finally, other promising medical strategies include using FK506, a nonsteroidal anti-inflammatory drug, to induce melanogenesis or using melanocyte-stimulating hormones with fractional laser-assisted drug deliveries, which are expected to emerge soon.

Comparison of two modalities of phototherapy, narrowband UV-B and PUVA in the treatment of psoriasis: A study from Western Uttar Pradesh

Introduction: PUVA (psoralen + UV-A) has been used since long time ago in psoriatic patients, which has some adverse effects. Phototherapy in form of Narrowband UVB is advancement in the treatment of psoriasis and it has been found to be same efficacious and having lesser side effects than PUVA. Aim: The study was aimed to compare NBUVB and PUVA in chronic plaque psoriasis in terms of their efficacy and adverse effects. Methods: The study included 43 cases of chronic plaque psoriasis which were randomly divided into two groups. Patients were examined for body surface area involvement and PASI scoring. Narrow-band UV-B phototherapy was given to one group and the other group received PUVA therapy thrice-weekly for a duration of 3 months. Then they were compared for clearance of lesions and side effects. Results: Both groups showed decrease in the PASI scoring by at least 75%. It was observed that lesser number of treatment sessions and fewer days were required for clearance of the lesions in PUVA group than the group receiving NBUVB therapy. But in NBUVB group, mean cumulative clearance dose and adverse reactions were significantly lower. The percentage of patients maintaining remission at six months were more in PUVA group as compared to NBUVB group. Conclusion: Both modes of phototherapy are useful in psoriasis. Patients got clearance of the lesions faster in the PUVA group but the side effects were markedly less in the NBUVB group. Keywords: Narrow-band UV-B, Psoralen UVA, Plaque psoriasis.

Tracing the Photoaddition of Pharmaceutical Psoralens to DNA.

The psoralens 8-methoxypsoralen (8-MOP), 4,5′,8-trimethylpsoralen (TMP) and 5-methoxypsoralen (5-MOP) find clinical application in PUVA (psoralen + UVA) therapy. PUVA treats skin diseases like psoriasis and atopic eczema. Psoralens target the DNA of cells. Upon photo-excitation psoralens bind to the DNA base thymine. This photo-binding was studied using steady-state UV/Vis and IR spectroscopy as well as nanosecond transient UV/Vis absorption. The experiments show that the photo-addition of 8-MOP and TMP involve the psoralen triplet state and a biradical intermediate. 5-MOP forms a structurally different photo-product. Its formation could not be traced by the present spectroscopic technique.

Psoralens activate and photosensitize Transient Receptor Potential channels Ankyrin type 1 (TRPA1) and Vanilloid type 1 (TRPV1).

PUVA (psoralen UVA) therapy is used to treat a variety of skin conditions, such as vitiligo psoriasis, eczema and mycosis fungoides, but it is frequently accompanied by phototoxicity leading to burning pain, itch and erythema. We used a combination of calcium and reactive oxygen species (ROS) imaging, patch clamp and neuropeptide release measurement to investigate whether certain ion channels involved in pain and itch signalling could be responsible for these adverese effects of PUVA. Clinically used psoralen derivatives 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen at physiologically relevant concentrations were able to activate and photosensitize two recombinant thermoTRP (temperature-gated Transient Receptor Potential) ion channels, TRPA1 (Transient Receptor Potential Ankyrin type 1) and TRPV1 (Transient Receptor Potential Vanilloid type 1). 8-MOP enhanced ROS production by UVA light, and the effect of 8-MOP on TRPA1 could be abolished by the antioxidant N-acetyl cysteine and by removal of critical cysteine residues from the N-terminus domain of the channel. Natively expressed mouse TRPA1 and TRPV1 both contribute to photosensitization of cultured primary afferent neurons by 8-MOP, while direct neuronal activation by this psoralen-derivative is mainly dependent on TRPV1. Both TRPA1 and TRPV1 are to a large extent involved in controlling 8-MOP-induced neuropeptide release from mouse trachea. Taken together our results provide a better understanding of the phototoxicity reported by PUVA patients and indicate a possible therapeutic approach to alleviate the adverse effects associated with this therapy. Our work provides evidence for the involvement of thermoTRP channels TRPA1 and TRPV1 in the activation and photosensitization of peripheral nociceptors during PUVA (Psoralen UVA) therapy.

Effectiveness and Safety of Psoralen-UVA (PUVA) Topical Therapy in Palmoplantar Psoriasis: A Report on 48 Patients

IntroductionPalmoplantar psoriasis is an uncommon clinical form of psoriasis. Although localized to the palms and soles, it has a considerable impact on the patient's function and quality of life. ObjectivesTo study the effectiveness and safety of psoralen-UV-A (PUVA) therapy in palmoplantar psoriasis and investigate predictors of clinical response. Material and methodsWe performed a retrospective chart review of all patients with palmoplantar psoriasis treated with topical PUVA therapy at our hospital between 2008 and 2011. Data were collected on effectiveness (using physician global assessment [PGA] scores), safety, and a range of clinical, epidemiological, and treatment-related variables. ResultsWe studied 48 patients (33 women and 15 men) with a mean age of 51 years. Treatment was considered to be effective (PGA score of 0 or 1) in 63% of cases. In addition to PUVA, systemic therapy was required in 47.9% of patients; the drug most often used was acitretin. Adverse effects were reported for 25% of patients during treatment. The most common effect was mild erythema, present in 18% of cases. ConclusionsIn our experience, topical PUVA is an appropriate treatment alternative for palmoplantar psoriasis; it offers similar response rates to systemic treatments, but has a better tolerance and safety profile. Associated systemic treatment, with acitretin in most cases, improved the probability of a satisfactory response to PUVA and should be considered in patients who do not respond adequately after 8 to 10 sessions.

Eficacia y seguridad en terapia con psoralen-UVA (PUVA) tópica en psoriasis palmoplantar. Experiencia en una serie de 48 pacientes

IntroductionPalmoplantar psoriasis is an uncommon clinical form of psoriasis. Although localized to the palms and soles, it has a considerable impact on the patient's function and quality of life. ObjectivesTo study the effectiveness and safety of psoralen-UV-A (PUVA) therapy in palmoplantar psoriasis and investigate predictors of clinical response. Material and methodsWe performed a retrospective chart review of all patients with palmoplantar psoriasis treated with topical PUVA therapy at our hospital between 2008 and 2011. Data were collected on effectiveness (using physician global assessment [PGA] scores), safety, and a range of clinical, epidemiological, and treatment-related variables. ResultsWe studied 48 patients (33 women and 15 men) with a mean age of 51 years. Treatment was considered to be effective (PGA score of 0 or 1) in 63% of cases. In addition to PUVA, systemic therapy was required in 47.9% of patients; the drug most often used was acitretin. Adverse effects were reported for 25% of patients during treatment. The most common effect was mild erythema, present in 18% of cases. ConclusionsIn our experience, topical PUVA is an appropriate treatment alternative for palmoplantar psoriasis; it offers similar response rates to systemic treatments, but has a better tolerance and safety profile. Associated systemic treatment, with acitretin in most cases, improved the probability of a satisfactory response to PUVA and should be considered in patients who do not respond adequately after 8 to 10 sessions.

Transdermal delivery of 8-methoxypsoralene mediated by polyamidoamine dendrimer G2.5 and G3.5—In vitro and in vivo study

In this work, we have focused on 8-methoxypsoralene (8-MOP) complexed with G2.5 and G3.5 poly(amido amine) (PAMAM) dendrimers. The purpose of this study was to investigate the efficacy of half-generation G2.5 and G3.5 PAMAM dendrimers conjugated with 8-MOP for delivery of 8-MOP in vitro study through polivinyldifluoride membrane (PVDE) and prepared pig ear skin (PES) using Franz diffusion and in vivo study through the skin of experimental animals (hairless rat skin). The tissue concentration of 8-MOP in hairless rat skin was analyzed by high performance liquid chromatography (HPLC) after 1 and 2 h. Detailed distribution of 8-MOP in skin layers and cellular structures were analyzed using laser scanning microscopy (CLSM). In vitro and in vivo studies showed that half-generation G2.5 and G3.5 PAMAM dendrimers are able to facilitate transdermal delivery of 8-MOP. G2.5 PAMAM dendrimer appeared to be more effective 8-MOP penetration enhancer than G3.5 PAMAM dendrimer, but in vivo the differences are not statistically significant. The concept of using G2.5 and G3.5 PAMAM dendrimers as carriers seems to be a promising method for the delivery of 8-MOP for PUVA (psoralen-UV-A) therapy.

Lipid Nanosystems in Topical PUVA Therapy

8-Methoxsalen was vehicled in nanoemulsion and in solid lipid nanoparticles (SLN) prepared by the hot homogenization technique in order to be used in topical psoralen UVA (PUVA) therapy. Drug entrapment efficiency in nanoparticles was improved by choosing the appropriate lipid matrix. The use of α-tocopherol in the lipid phase reduces 8-methoxsalen induced photooxidation of porcine skin, which was evaluated in vitro by a malondialdehyde (MDA) test: This result is promising to reduce in vivo human skin irritation after PUVA therapy, which can be attributed to skin photooxidation.

Association of systemic psoriasis therapies and incidence of myocardial infarction

Funding sources: None. Conflicts of interest: J.C.C. and F.D., none declared. J.J.W. has received research funding from Abbott Laboratories, Amgen and Pfizer, which were not directly related to this letter. Madam, We read with much interest the article by Abuabara et al.1 on the effect of systemic psoriasis therapies on the incidence of myocardial infarction (MI). Using the database of a large U.S. insurer that included 25 554 patients with psoriasis receiving systemic treatment or phototherapy, this study is one of the first in the literature to examine this question. We laud the authors for their efforts in the study, but we believe that the authors’ conclusion that there does not appear to be a reduced risk of MI in patients with psoriasis receiving systemic therapy compared with a group undergoing phototherapy is incorrect based on flaws in the study design. The therapies studied and methods of analysis raise several concerns. The authors compared the risk of acute MI in patients receiving ‘systemic therapies’ (methotrexate, ciclosporin, alefacept, efalizumab, adalimumab, etanercept and infliximab) with those receiving ultraviolet (UV) B phototherapy. There is some evidence that methotrexate2 and tumour necrosis factor (TNF)‐α inhibitors may reduce MI risk (Wu JJ, Poon KT, Dann F et al. Association between TNF‐α inhibitor therapy and myocardial infarction risk in patients with psoriasis. Submitted for publication). Ciclosporin increases blood pressure and lipids, and efalizumab raises C‐reactive protein,3 a marker for inflammation, increasing the risk for MI. Therefore, grouping all systemic therapy together to compare against phototherapy is not ideal as the benefits of one systemic therapy may mask the risks of another. Secondly, due to the intrinsic differences in the nature of the therapies and the economic windfall, the more important question to be asked is whether TNF‐α inhibitor therapy may reduce the risk of MI incidence when compared with oral therapy or phototherapy. The systemic therapy acitretin was not included in the study. Acitretin may increase triglyceride levels, which could affect MI risk. There was no mention of psoralen + UVA therapy (PUVA). PUVA can be considered a systemic therapy due to ingestion of psoralen prior to exposure to UVA, but it can also be considered phototherapy. There is no reconciliation of which cohort patients treated with PUVA might have been grouped.

Psoralen-ultraviolet A therapy alters epidermal Sema3A and NGF levels and modulates epidermal innervation in atopic dermatitis

Epidermal nerve densities are increased in patients with atopic dermatitis (AD), suggesting that it is partly responsible for the intense itching in the skin. Epidermal hyperinnervation in AD patients is decreased by ultraviolet (UV) phototherapy, although the underlying mechanisms are poorly understood. Interestingly, abnormal expression of axonal guidance molecules, such as nerve growth factor (NGF) and semaphorin 3A (Sema3A), is found in the epidermis of AD patients. Therefore, UV phototherapy may alter levels of axonal guidance molecule expression in atopic skin. This study was performed to investigate whether epidermal Sema3A and NGF levels in AD are influenced by psoralen-UVA (PUVA) therapy. Skin biopsies obtained from chronic AD patients before and after PUVA therapy were used. Both Sema3A and NGF in the skin were examined at mRNA and protein levels by quantitative RT-PCR and immunohistochemistry, respectively. Nerve fibers in the skin were stained with anti-PGP9.5 antibody, and the number of epidermal nerve fibers was counted. PUVA therapy decreased epidermal nerve densities in AD patients, concomitant with decreases in both visual analog scale (VAS) scores for pruritus and clinical severity scores. Increased fluorescence intensity of Sema3A and decreased fluorescence intensity of NGF were observed in the epidermis of PUVA-treated group. Moreover, Sema3A mRNA levels were upregulated in the PUVA-treated skins compared with untreated controls, while NGF mRNA levels in the skin were downregulated by the treatment. PUVA therapy may reduce epidermal hyperinnervation of AD by normalization of abnormal Sema3A and NGF expression in the epidermis.

Singlet oxygen generation in PUVA therapy studied using electronic structure calculations

The ability of furocoumarins to participate in the PUVA (Psoralen+UV-A) therapy against skin disorders and some types of cancer, is analyzed on quantum chemical grounds. The efficiency of the process relies on its capability to populate its lowest triplet excited state, and then either form adducts with thymine which interfere DNA replication or transfer its energy, generating singlet molecular oxygen damaging the cell membrane in photoactivated tissues. By determining the spin–orbit couplings, shown to be the key property, in the intersystem crossing yielding the triplet state of the furocoumarin, the electronic couplings in the triplet–triplet energy transfer process producing the singlet oxygen, and the reaction rates and lifetimes, the efficiency in the phototherapeutic action of the furocoumarin family is predicted as: khellin<5-methoxypsoralen (5-MOP)<8-methoxypsoralen (8-MOP)<psoralen<4,5′,8-trimethylpsoralen (TMP)<3-carbethoxypsoralen (3-CPS), the latter being the most efficient photosensitizer and singlet oxygen generator.

Narrowband Ultraviolet B Therapy in Psoriasis: Reality, Outlook, and Uncertainty

Developed and perfected as a specific treatment for psoriasis, narrowband ultraviolet B (UV-B) therapy entered the clinical practice of dermatology back in the last century, at the beginning of the 1980s. The hindsight afforded by a certain distance allows us to state that the arguments underlying the use of this treatment, that is, a peak close to 311 nm is the ideal UV-B band for the treatment of psoriasis, would prove more than debatable from a strictly scientific standpoint. Thus, the studies on which this paradigm was based had very small samples, and their methodology was not sufficiently rigorous to support such a forceful statement. 1,2 Nevertheless, the history of medicine has occasionally shown that weakness in the concept is compensated by the benefit of experience. Thus, the evidence gathered over a short period proved sufficient to conclude that the old broadband UV-B therapy was surpassed both in efficacy and in ease of use by the then novel narrowband UV-B therapy, at least when the usual TL12 lamps (broadband UV-B) were compared with the TL01 lamps (narrowband UV-B). This nuance will be discussed below. 3 The good results obtained compared to broadband UV-B therapy encouraged phototherapists to consider the new arrival as an interesting and powerful option, capable of challenging the—until then—undisputed psoralen UV-A therapy (or PUVA, that is, psoralens combined with UV-A). For almost 20 years, PUVA was considered the most effective treatment in the moderate and severe forms of psoriasis, not only with respect to other types of phototherapy, but also when compared with the available pharmacologic alternatives. Comparisons aside, and although we could cite methodologic nuances, an assessment of the most rigorous studies has shown some advantage for the old PUVA, in terms both of efficacy and of duration of response, which was longer the more severe the psoriasis. 4 However, this circumstance did not prevent

A biological approach in a patient with psoriasis and bullous pemphigoid associated with losartan therapy

Several cases of psoriasis associated with bullous disorders have been reported, and it is clearly recognized that bullous pemphigoid (BP) is the most common bullous disorder observed in association with psoriasis, especially after ultraviolet (UV)B and psoralen UVA therapy. Moreover, other medications have been repeatedly reported to induce bullous diseases, especially pemphigus vulgaris. We report for the first time a case of BP possibly induced by losartan, an angiotensin II antagonist, in a patient with a severe psoriatic background. Angiotensin II type 1 receptor antagonists belong to a new class of drug for hypertension or congestive heart failure with established efficacy and few side-effects. Coexistence of psoriasis vulgaris with bullous diseases represents also a difficult therapeutic challenge. This rare case of psoriasis and generalized BP triggered by a sartan drug was treated with rituximab and etanercept.

Randomized Double-blind Trial of Treatment of Vitiligo

To compare the efficacy of oral psoralen-UV-A (PUVA) with that of narrowband-UV-B (NB-UVB) phototherapy in patients with nonsegmental vitiligo. Double-blind randomized study. Phototherapy unit in a university hospital. Fifty-six patients with nonsegmental vitiligo. Interventions Twice-weekly therapy with PUVA or NB-UVB. The change in body surface area affected by vitiligo and the color match of repigmented skin compared with unaffected skin were assessed after 48 sessions of therapy, at the end of the therapy course, and 12 months after the end of therapy. The results in the 25 patients each in the PUVA and NB-UVB groups who began therapy were analyzed. The median number of treatments was 47 in the PUVA-treated group and 97 in the NB-UVB-treated group (P = .03); we suspect this difference was because of the differences in efficacy and adverse effects between the 2 modalities, such that patients in the NB-UVB group wanted a longer course of treatment. At the end of therapy, 16 (64%) of 25 patients in the NB-UVB group showed greater than 50% improvement in body surface area affected compared with 9 (36%) of 25 patients in the PUVA group. The color match of the repigmented skin was excellent in all patients in the NB-UVB group but in only 11 (44%) of those in the PUVA group (P<.001). In patients who completed 48 sessions, the improvement in body surface area affected by vitiligo was greater with NB-UVB therapy than with PUVA therapy (P = .007). Twelve months after the cessation of therapy, the superiority of NB-UVB tended to be maintained. In the treatment of nonsegmental vitiligo, NB-UVB therapy is superior to oral PUVA therapy.

Randomized Double-blind Trial of the Treatment of Chronic Plaque Psoriasis: Efficacy of Psoralen–UV-A Therapy vs Narrowband UV-B Therapy

Randomized Double-blind Trial of the Treatment of Chronic Plaque Psoriasis: Efficacy of Psoralen–UV-A Therapy vs Narrowband UV-B Therapy

Randomized Double-blind Trial of the Treatment of Chronic Plaque Psoriasis

To compare the efficacy of oral psoralen-UV-A (PUVA) therapy with that of narrowband UV-B (NB-UVB) therapy in patients with chronic plaque psoriasis. Double-blind randomized study. Phototherapy unit in a university hospital. Patients Ninety-three patients with chronic plaque psoriasis. Interventions Twice-weekly NB-UVB or PUVA therapy, starting at 70% of the minimum phototoxic or erythema dose, with 20% incremental increases. Patients were treated until clearance, up to a maximum of 30 sessions; those with clearance were followed up until relapse or for 12 months. Proportion of patients achieving clearance, number of treatments to clearance, and, among those with clearance, the proportion remaining in remission at 6 months. Patients with skin types V and VI had a lower rate of clearance than those with skin types I through IV (24% vs 75%; P = .001). In patients with skin types I through IV, PUVA was significantly more effective than NB-UVB at achieving clearance (84% vs 65%; P = .02). The median number of treatments to clearance was significantly lower in the PUVA group (17.0 vs 28.5; P<.001). More patients treated with PUVA vs NB-UVB were reported to have erythema at some stage during treatment (49% vs 22%; P = .004), although this difference may have been due to ascertainment bias. Six months after the cessation of therapy, 68% of PUVA-treated patients were still in remission vs 35% of NB-UVB-treated patients. Conclusion Compared with NB-UVB, PUVA achieves clearance in more patients with fewer treatment sessions and results in longer remissions.

Narrowband UVB and cream psoralen-UVA combination therapy for plaque-type psoriasis

Background Psoralen-UVA (PUVA) and narrowband UVB (311-nm) therapy are considered to be first-line phototherapies for patients with moderate to severe psoriasis. To reduce side effects as a result of systemic resorption of psoralens, topical PUVA therapies have been developed and proven to be effective in the treatment of psoriasis. Objective We sought to evaluate the combination therapy of narrowband UVB plus cream PUVA on selected psoriatic plaques compared with narrowband UVB or cream PUVA alone. Methods A total of 30 patients (Psoriasis Area and Severity Index score of 8-15) were included in the randomized study. The combination therapy consisting of narrowband UVB whole-body irradiation followed by cream PUVA therapy for selected psoriatic plaques was evaluated in 10 patients with chronic plaque-stage psoriasis. For comparison, the therapeutic efficacy, number of treatments, and cumulative UV doses until remission (Psoriasis Area and Severity Index score < 4) of cream PUVA therapy or narrowband UVB alone was determined in 10 patients, respectively. Results Both monotherapies induced clearance of psoriatic lesions in all patients within 5 to 7 weeks. Mean number of treatments for cream PUVA was 24 ± 5; for narrowband UVB was 21 ± 3. The mean cumulative UVA dose was 45.0 ± 16.3 J/cm 2 and the mean cumulative UVB dose was 17.1 ± 4.1 J/cm 2. Combination therapy resulted in complete clearance of lesions in all patients after 3 to 4 weeks. Mean number of treatment was 14 ± 2, mean cumulative UVA dose was 18.7 ± 4.7 J/cm 2, and mean cumulative UVB dose was 8.2 ± 3.3 J/cm 2. The number of treatments ( P < .001, analysis of variance), UVA dose ( P < .001, t test), and UVB dose ( P < .001, t test) were significantly reduced compared with both monotherapies. Conclusions Our results indicate that a combination therapy of narrowband UVB plus cream PUVA appears to have a significantly higher efficacy compared with either monotherapy. The cumulative UV doses were significantly lower in the combination therapy. We conclude that cream PUVA can be used in addition to narrowband UVB for areas that tend to clear less quickly than the rest of the body.

Psychological Distress Impairs Clearance of Psoriasis in Patients Treated With Photochemotherapy

To assess whether psychological distress affects treatment outcome in psoriasis. Cohort study of patients with psoriasis receiving psoralen-UV-A (PUVA) photochemotherapy. Two university hospital dermatology departments. One hundred twelve patients with chronic plaque psoriasis. We assessed clinical severity of psoriasis, psychological distress, and other potential confounders of treatment outcome such as skin phototype, family history of psoriasis, and alcohol intake before starting PUVA therapy. Clinical severity of disease and response to therapy were assessed at every fourth appointment. Pathological or high-level worry was the only significant (P =.01) predictor of time taken for PUVA to clear psoriasis. Event curves of time to clearance significantly differed between high- and low-level worry groups (log rank test, 6.64; df = 1; P =.01). Patients in the high-level worry group cleared with PUVA treatment at a rate 1.8 times slower than that of the low-level worry group (ExpB = 1.81; 95% confidence interval, 1.13-2.90). Fiftieth percentile time to clearance of psoriasis in the high- and low-level worry groups showed a median difference of 19 days. Psychological distress, in the form of excessive worrying, has a significant and detrimental affect on treatment outcome in patients with psoriasis. Patients with psoriasis who are classified as high-level worriers may benefit from adjunctive psychological intervention before and during treatment. These findings provide further evidence of the existence of a brain-skin axis.

Measurement of the capillary blood cell velocity with a new laser Doppler anemometer in human skin capillaries outside the cuticle of the nail

The ability of furocoumarins to participate in the PUVA (Psoralen + UV-A) therapy against skin disorders and some types of cancer, is analyzed on quantum chemical grounds. The efficiency of the process relies on its capability to populate its lowest triplet excited state, and then either form adducts with thymine which interfere DNA replication or transfer its energy, generating singlet molecular oxygen damaging the cell membrane in photoactivated tissues. By determining the spin–orbit couplings, shown to be the key property, in the intersystem crossing yielding the triplet state of the furocoumarin, the electronic couplings in the triplet–triplet energy transfer process producing the singlet oxygen, and the reaction rates and lifetimes, the efficiency in the phototherapeutic action of the furocoumarin family is predicted as: khellin < 5-methoxypsoralen (5-MOP) < 8-methoxypsoralen (8-MOP) < psoralen < 4,5′,8-trimethylpsoralen (TMP) < 3-carbethoxypsoralen (3-CPS), the latter being the most efficient photosensitizer and singlet oxygen generator.

Photoionization and Photosensitized Electron-Transfer Reactions of Psoralens and Coumarins

The radical cations of several psoralens (furocoumarins) and coumarins have been generated via direct excitation (λex = 355 nm) in aqueous solution and/or via photosensitized electron transfer in acetonitrile and characterized using transient absorption spectroscopy. Significant photoionization yields were observed for 8-methoxypsoralen (8-MOP) and three methoxy-substituted coumarins in aqueous buffer and for 4,5‘,8-trimethylpsoralen in aqueous acetonitrile. Of those, 6,7-dimethoxycoumarin (67-DMC) was found to have the highest quantum (0.2 ± 0.03) yield for photoionization in aqueous buffer following direct excitation at both 355 and 308 nm. Laser energy dependence plots for the photoionization process are linear and pass through (0,0) for λex = 355, 308, and 266 nm, providing strong evidence for a monophotonic process. The photoionization results are compared with both the one-electron oxidation potentials of the compounds (obtained via cyclic voltammetry) and the fluorescence quantum yields and lifetimes (obtained via single photon counting). The results demonstrate that photoionization is of general importance in psoralen and coumarin photochemistry and varies substantially in efficiency, depending on the structure, photophysical parameters, and environment of the substrate. The observation of photoionization upon low-intensity UVA irradiation is clearly significant with respect to the clinical use of these compounds in psoralen UVA therapy.