Main Photoproducts Research Articles

Riboflavin as a Coloring Agent of Tablets Affects the Photostability of Manidipine after the Change of Dosage Forms

Manidipine (MP) is widely used for reducing high blood pressure. Calslot® (CALS) tablets, which are the original MP medicines, and their generic medicines have been used for patients in clinical situations. The authors hypothesized that the photodegradability of MP drug substance in CALS tablets might be enhanced when the tablets were photo-exposed after the change of the dosage form by the presence of riboflavin (RF), which is utilized as a coloring agent and a well-known photosensitizer. The present study clarified that RF enhanced the photodegradation of MP when the powders and the suspensions of CALS tablets were ultraviolet light (UV) irradiated. The addition of RF to the suspension of MP standard substances also promoted MP photodegradation along with the increase of the generation rate of its main photoproduct, benzophenone. Finally, the authors performed the photostabilization of MP suspensions based on the addition of quercetin (QU), which is one of polyphenols and has both the antioxidative potency and the UV filtering potency. It is summarized that QU has a protective potency for MP’s own photodegradation, and it partially suppresses the photocatalytic effect of RF. Further studies focused on the photochemical behaviors of utilized additives for medicines are needed for their safe use.

Using a multistate mapping approach to surface hopping to predict the ultrafast electron diffraction signal of gas-phase cyclobutanone.

Using the recently developed multistate mapping approach to surface hopping (multistate MASH) method combined with SA(3)-CASSCF(12,12)/aug-cc-pVDZ electronic structure calculations, the gas-phase isotropic ultrafast electron diffraction (UED) of cyclobutanone is predicted and analyzed. After excitation into the n-3s Rydberg state (S2), cyclobutanone can relax through two S2/S1 conical intersections, one characterized by compression of the CO bond and the other by dissociation of the α-CC bond. Subsequent transfer into the ground state (S0) is then achieved via two additional S1/S0 conical intersections that lead to three reaction pathways: α ring-opening, ethene/ketene production, and CO liberation. The isotropic gas-phase UED signal is predicted from the multistate MASH simulations, allowing for a direct comparison to the experimental data. This work, which is a contribution to the cyclobutanone prediction challenge, facilitates the identification of the main photoproducts in the UED signal and thereby emphasizes the importance of dynamics simulations for the interpretation of ultrafast experiments.

Predicting the photodynamics of cyclobutanone triggered by a laser pulse at 200nm and its MeV-UED signals-A trajectory surface hopping and XMS-CASPT2 perspective.

This work is part of a prediction challenge that invited theoretical/computational chemists to predict the photochemistry of cyclobutanone in the gas phase, excited at 200nm by a laser pulse, and the expected signal that will be recorded during a time-resolved megaelectronvolt ultrafast electron diffraction (MeV-UED). We present here our theoretical predictions based on a combination of trajectory surface hopping with XMS-CASPT2 (for the nonadiabatic molecular dynamics) and Born-Oppenheimer molecular dynamics with MP2 (for the athermal ground-state dynamics following internal conversion), coined (NA+BO)MD. The initial conditions were sampled from Born-Oppenheimer molecular dynamics coupled to a quantum thermostat. Our simulations indicate that the main photoproducts after 2ps of dynamics are CO + cyclopropane (50%), CO + propene (10%), and ethene and ketene (34%). The photoexcited cyclobutanone in its second excited electronic state S2 can follow two pathways for its nonradiative decay: (i) a ring-opening in S2 and a subsequent rapid decay to the ground electronic state, where the photoproducts are formed, or (ii) a transfer through a closed-ring conical intersection to S1, where cyclobutanone ring opens and then funnels to the ground state. Lifetimes for the photoproduct and electronic populations were determined. We calculated a stationary MeV-UED signal [difference pair distribution function-ΔPDF(r)] for each (interpolated) pathway as well as a time-resolved signal [ΔPDF(r,t) and ΔI/I(s,t)] for the full swarm of (NA+BO)MD trajectories. Furthermore, our analysis provides time-independent basis functions that can be used to fit the time-dependent experimental UED signals [both ΔPDF(r,t) and ΔI/I(s,t)] and potentially recover the population of photoproducts. We also offer a detailed analysis of the limitations of our model and their potential impact on the predicted experimental signals.

Synthesis, self-assembly, and characterization of backbone photocleavable polyacylhydrazones

Polymers capable of undergoing rapid degradation after exposure to light irradiation hold great promise in a plethora of applications including biomedical materials, smart coatings and hydrogels, degradable plastics, and others. Herein, the synthesis of new light-degradable polyacylhydrazones comprising alternating hydrophilic poly(ethylene glycol) (PEG) segments and hydrophobic aromatic units, are presented. A polycondensation reaction between diacylhydrazide terminated poly(ethylene glycols) (Mn = 4000 and 1500 g mol-1) with aromatic dicarbonyl comonomers was employed for the synthesis of the amphiphilic polyacylhydrazones. By increasing the number of aromatic moieties in close proximity to the acylhydrazone bonds and varying the type, dialdehyde vs diketone, and the conjugation length of the hydrophobic comonomers, the absorption maximum of the copolymers was shifted to longer wavelengths. The amphiphilic polyacylhydazones derived from the PEG with Mn = 4000 g mol-1 self-assembled in water into spherical nanoparticles, evidenced by SEM and DLS. Finally, light irradiation of the polymer assemblies induced the photocleavage of the acylhydrazone bonds along the polymer backbone, which led to the dissociation of the polymer nanoparticles and the formation of a PEG derivative as the main photoproduct.

A First Proposal on the Nitrobenzene Photorelease Mechanism of NO2 and Its Relation to NO Formation through a Roaming Mechanism.

Despite the fact that NO2 is considered to be the main photoproduct of nitrobenzene photochemistry, no mechanism has ever been proposed to rationalize its formation. NO photorelease is instead a more studied process, probably due to its application in the drug delivery sector and the study of roaming mechanisms. In this contribution, a photoinduced mechanism accounting for the formation of NO2 in nitrobenzene is theorized based on CASPT2, CASSCF, and DFT electronic structure calculations and CASSCF classical dynamics. A triplet nπ* state is shown to evolve toward C-NO2 dissociation, being, in fact, the only low-lying excited state favoring such a deformation. Along the triplet dissociation path, the possibility to decay to the singlet ground state results in the frustration of the dissociation and in the recombination of the fragments, either back to the nitro or the nitrite isomer. The thermal decomposition of the latter to NO constitutes globally a roaming mechanism of NO formation.

Salicylideneaniline/Dithienylethene Hybrid Molecular Switches: Design, Synthesis, and Photochromism.

A hybrid molecular switch comprising salicylideneaniline (SA) and dithienylethene (DTE) moieties around a single benzene ring is reported. Due to an interplay between solvent-assisted enol-keto tautomerization in the former moiety and photochromic electrocyclization in the latter, this dithienylbenzene derivative was found to be photoresponsive at room temperature with a thermally stable closed form. The main photoproduct featuring ring-closed DTE and keto-enamine SA structures could be isolated and converted back to the starting material by irradiation with visible light. The optical properties of the potential structures involved in the overall process were characterized by using density functional theory (DFT) calculations in good agreement with the measured data. The reversibility of the conversion could be tuned by the presence of donor and acceptor substituents, while the introduction of the imine in the form of a benzothiazole moiety enabled photochemistry even in nonprotic solvents.

Study of the photoreaction of new triazene derivatives in solution and in polymer binder

• New aryltriazenes are synthesized and fully characterized in solution by means of different analytical techniques. • The photoreactivity depends on the kind and position of the chemical substituents of the phenyl ring and on the solvent used. • The photoproducts are evaluated using GC-MS and they depends on the solvent used. • The light induced reaction of the nitro derivative is performed in polymer matrices. • The reactivity changes with the polymer used. Triazenes are molecular systems that undergo a photolysis with the evolution of molecular nitrogen. A set of aryltriazene bearing different substituents are synthesized and characterized. The photoreaction is studied in solution by means of UV-vis spectroscopy showing a large dependence of required doses and UV-vis spectrum evolution on the substituent position and character. The structural changes upon the photolysis are also probed using vibrational spectroscopy (IR and Raman). Moreover, GC-MS spectroscopy is employed to retrieve the structure of the main photoproducts. The most promising derivative, in terms of stability and band position is incorporated in different polymer matrices, both thermosetting and thermoplastic; its photoreaction is studied in correlation with the polymer structure.

Stereospecific Formation of the rctt Isomer of Bis-crown-Containing Cyclobutane upon [2 + 2] Photocycloaddition of an (18-Crown-6)stilbene Induced by Self-Assembly via Hydrogen Bonding.

The formation and the spectroscopic and structural properties of 1:1 and 2:1 (ligand-to-dication) complexes of an (18-crown-6)stilbene with ethane-1,2-diammonium diperchlorate in MeCN were studied by UV-vis and NMR spectroscopy and by density functional theory calculations. Prolonged UV irradiation of 2:1 mixtures of the crown stilbene and the diammonium salt led to the formation of two main photoproducts, namely, the single syn-"head-to-head" photodimer of the crown stilbene (rctt cyclobutane) due to supramolecular-assisted [2 + 2] photocycloaddition and a crown ether derivative of phenanthrene due to a photoinduced electrocyclization reaction. The rctt cyclobutane was isolated by preparative photolysis, followed by chromatography. The selectivity of the [2 + 2] photocycloaddition is explained by supramolecular pre-organization of crown stilbene molecules into the 2:1 complexes that have a pseudo-sandwich structure with stacking interactions between the stilbene moieties.

Structure, Spectra and Photochemistry of 2-Amino-4-Methylthiazole: FTIR Matrix Isolation and Theoretical Studies.

The structure, tautomerization pathways, vibrational spectra, and photochemistry of 2-amino-4-methylthiazole (AMT) molecule were studied by matrix isolation FTIR spectroscopy and DFT calculations undertaken at the B3LYP/6-311++G(3df,3pd) level of theory. The most stable tautomer with the five-membered ring stabilized by two double C=C and C=N bonds, was detected in argon matrices after deposition. When the AMT/Ar matrices were exposed to 265 nm selective irradiation, three main photoproducts, N-(1-sulfanylprop-1-en-2-yl)carbodiimide (fp1), N-(1-thioxopropan-2-yl)carbodiimide (fp2) and N-(2-methylthiiran-2-yl)carbodiimide (fp3), were photoproduced by a cleavage of the CS–CN bond together with hydrogen atom migration. The minor photoreaction caused by the cleavage of the CS–CC bond and followed by hydrogen migration formed 2-methyl-1H-azirene-1-carbimidothioic acid (fp15). We have also found that cleavage of the CS–CN bond followed by disruption of the N–C bond produced cyanamide (fp11) and the C(CH3)=CH–S biradical that transformed into 2-methylthiirene (fp12) and further photoreactions produced 1-propyne-1-thiole (fp13) or methylthioketene (fp14). Cleavage of the CS–CC bond followed by disruption of the N–C bond produced propyne (fp22) and the S–C(NH2)=N biradical that transformed into 3-aminethiazirene (fp23); further photoreactions produced N-sulfanylcarbodiimide (fp25). As a result of these transformations, several molecular complexes were identified as photoproducts besides new molecules in the AMT photolysis process.

Photoinduced [6π]-Electrocyclic Reaction of Mono-, Di-, and Trisubstituted Triphenylamines in Acetonitrile. A Steady-State Investigation.

Direct irradiation of mono-, di-, and trisubstituted triphenylamine derivatives in acetonitrile as solvent with light of 254 nm has been systematically investigated, revealing that the exo/endo carbazole derivatives were formed as the main photoproducts from modest to good yields for triphenylamines substituted with electron-donor and neutral substituents. The kinetic profiles of the photoreaction were also recorded, and the consumption rate constants (k) were measured. These kinetic parameters show dependence on the nature of the substituents, and linear Hammett correlations were carried out to showcase the substituent effect. On the other hand, the spectroscopic behavior of the electron-rich substituted triphenylamines has been analyzed, suggesting that the fluorescence emission spectra display a mirror image of the lower energy absorption bands, while for those amines bearing electron-acceptor groups the formation of charge-transfer complexes and their fluorescence emissions constitute the main deactivation pathway of the photoreaction.

Biomimetic photooxidation of noscapine sensitized by a riboflavin derivative in water: The combined role of natural dyes and solar light in environmental remediation.

Noscapine (NSC) is a benzyl-isoquinoline alkaloid discovered in 1930 as an antitussive agent. Recently, NSC has also been reported to exhibit antitumor activity and, according to computational studies, it is able to attack the protease enzyme of Coronavirus (COVID-19) and thus could be used as antiviral for COVID-19 pandemic. Therefore, an increasing use of this drug could be envisaged in the coming years. NSC is readily metabolized with a half-life of 4.5h giving rise to cotarnine, hydrocotarnine, and meconine, arising from the oxidative breaking of the CC bond between isoquinoline and phthalide moieties. Because of its potentially increasing use, high concentrations of NSC but also its metabolites will be delivered in the environment and potentially affect natural ecosystems. Thus, the aim of this work is to investigate the degradation of NSC in the presence of naturally occurring photocatalysts. As a matter of fact, the present contribution has demonstrated that NSC can be efficiently degraded in the presence of a derivative of the natural organic dye Riboflavin (RFTA) upon exposure to visible light. Indeed, a detailed study of the mechanism involved in the photodegradation revealed the similarities between the biomimetic and the photocatalyzed processes. In fact, the main photoproducts of NSC were identified as cotarnine and opianic acid based on a careful UPLC-MS2 analysis compared to the independently synthesized standards. The former is coincident with one of the main metabolites obtained in humans, whereas the latter is related to meconine, a second major metabolite of NSC. Photophysical experiments demonstrated that the observed oxidative cleavage is mediated mainly by singlet oxygen in a medium in which the lifetime of 1O2 is long enough, or by electron transfer to the triplet excited state of RFTA if the photodegradation occurs in aqueous media, where the 1O2 lifetime is very short.

Tungsten Catalysts for Visible Light Driven Ofloxacin Photocatalytic Degradation and Hydrogen Production

Some tungsten catalysts of interest that are synthesized are bismuth tungstate (BT) and Tetrabutylammonium decatungstate (TBADT), using two consolidated procedures. BT is used as a photo-catalyst for the simulated solar light degradation of ofloxacin (OFL) antibiotic under relevant real conditions (µg L−1, fresh water) with the limit of 0.05 g L−1 of catalyst. A quantitative drug decomposition occurred following a bi-exponential first-order law, with an efficiency comparable with the most used P25 TiO2 catalyst. The photocatalytic profiles of OFL at µg L−1 and mg L−1 were monitored by high-pressure liquid chromatography (HPLC) coupled with fluorescence (FD) and ultraviolet (UV) detectors. Additionally, the main photoproducts were identified by high-pressure liquid chromatography coupled to electrospray ionization in tandem with mass spectrometry (HPLC-ESI-MS/MS). The catalyst Tetrabutylammonium decatungstate (TBADT) was used as a catalyst to produce hydrogen from glucose and 2-propanol in aqueous solution, providing hydrogen gas evolution up to 10 µmol g−1 h−1.

The Photoinduced Electrocyclization Reaction of Triphenylamine (TPA) in Sustainable and Confined Micellar Solutions: A Steady‐State and Laser Flash Photolysis Approach

AbstractThe irradiation of triphenylamine (TPA) under homogeneous (cyclohexane, acetonitrile and methanol) and micellar [sodium dodecyl sulfate (SDS), cetyltrimethylammonium chloride (CTAC) and polyethylene glycol monododecyl ether (Brij‐P35)] conditions has been investigated through a combined steady‐state and time‐resolved spectroscopic approach. Photolysis of TPA at 254 nm in different media afforded N‐phenylcarbazole (N−PhCA) as the main photoproduct, and when the photoreaction of TPA was carried out in micellar solution the relative rate of formation of N−PhCA was found to be faster than in homogeneous media due to the environmental confined and hydrophobic micellar core. On the other hand, the transient N‐phenyl‐4a,4b‐dihydrocarbazole (DHC0) was detected and fully characterized via laser flash photolysis. Finally, the location of TPA within the hydrophobic core of the micelle was investigated by 1D and 2D NMR spectroscopic analyses.

Kinetics of the photolysis of pyridaben and its main photoproduct in aqueous environments under simulated solar irradiation.

The photolytic fate of pyridaben and its main photolysis product was investigated in different aqueous solutions. Results showed that the photolysis of pyridaben followed pseudo first-order kinetics or the hockey-stick model. In buffer solutions, the half-life of pyridaben was the shortest at pH 4, while the degradation rate within 24 h was the highest at pH 9. Humic acids (HA) at concentrations of 1–20 mg L−1 favored the photolysis of pyridaben while fulvic acids (FA) did not have a significant effect. Nitrate at low concentrations (0.01 mM) accelerated the photolysis and Fe(iii) at high concentrations (0.01 and 0.1 mM) significantly inhibited the photolysis. The photolysis rate of pyridaben in rainwater, tap water, and river water was significantly higher than that in distilled water. The half-lives in distilled water, rainwater, tap water, river water, and pond water were 2.36, 1.36, 1.61, 1.77, and 2.68 h, respectively. Ultra-high-performance liquid chromatography/high-resolution mass spectrometry identified M328 as a photolysis product. The degradation of M328 followed pseudo first-order kinetics in distilled water, buffer solutions and aqueous solutions fortified with HA. The half-lives of M328 were in the range of 7.07–13.95 h. These results are essential for further environmental risk assessment of pyridaben.

Wavelength‐dependent photochemistry of 1‐phenyl‐1‐diazopropane

Abstract1‐Phenyl‐1‐diazopropane (PDP) was photolyzed in acetonitrile/methanol mixtures using either 520‐nm light or 350‐nm light. The main photoproducts were 1‐methoxypropylbenzene and E,Z‐1‐phenylpropene. With 520‐nm light, a plot of (1‐methoxypropylbenzene)/(E,Z‐1‐phenylpropene) versus methanol concentration was linear. These results are consistent with the visible light induced fragmentation of PDP to dinitrogen and closed shell singlet (S0) ethyl, phenylcarbene (1EPC) which partitions between 1,2 hydrogen migration to form alkene, and reaction with methanol to form ether. The same plot generated with 350‐nm light significantly deviates from linearity. It is proposed that 350‐nm light generates the carbene in a vibrationally excited, open shell S1 excited state (1EPC*). This state rearranges to E,Z‐1‐phenylpropenes in competition with relaxation to ground state 1EPC over a few tens of ps. As a result, methanol cannot completely suppress alkene formation upon photolysis of PDP with 350‐nm light. The carbene excited state is a “non‐trappable carbene” route to alkenes.

Induced selectivity in the photochemistry of estrone derivatives in sustainable and micellar environment: preparative and mechanistic studies

In this study, we carried out preparative and mechanistic studies on the photochemical reaction of a series of 3-acylestrone derivatives in confined and sustainable micellar environment under steady-state conditions and the results were compared with those obtained in cyclohexane solution. The aim of this work is mainly focused to show whether the nature of the surfactant (cationic, neutral and anionic) leads to noticeable selectivity in the photoproduct formation. The 3-acylestrone derivatives underwent the photo-Fries rearrangement, with concomitant homolytic fragmentation of the ester group and [1;3]-acyl migration. This pathway afforded the ortho-acyl estrone derivatives, the main photoproducts together with estrone. However, epimerization of the ortho regioisomer 2-acetylestrone and estrone through Norrish Type I photoreaction occurred involving the fragmentation of the C-α at the carbonyl group (C-17) of the steroid. UV-visible and 2D-NMR (NOESY) spectroscopies have been employed to measure the binding constant Kb and the location of the steroids within the hydrophobic core of the micelle.

Structure determination of clinofibrate photoproducts generated by ultraviolet-light irradiation in aqueous media

Photodegradation of clinofibrate, which is one of the fibrate drugs, was evaluated and chemical structures of its photoproducts were determined. Clinofibrate in aqueous media was photodegraded gradually by the UV light emission with the generation of several photoproducts. The result of HPLC analysis indicated that some photoproducts were more photostable compared with the parent compound. After 14 days irradiation, clinofibrate was degraded completely while several photoproducts were remained in the test solution. Structure determination of nine photoproducts was performed by means of ESI-LC/MS/MS analysis. Main photoproduct of clinofibrate was 2-(4-(1-(4-hydroxyphenyl)cyclohexyl)phenoxy)-2-methylbutanoic acid. Structure determination of clinofibrate photoproducts made it possible the estimation of the photodegradation pathway. It was tempting to speculate that the main photoproduct was generated by the elimination of 2-methylbutanoic acid and other photoproducts were generated through several photochemical reactions including further elimination of 2-methylbutanoic acid and decarboxylation. The obtained results will be helpful for the further research focused on the evaluation of biological activities of clinofibrate photoproducts, photostability of clinofibrate in commercial tablets and changed formulations, and the photostabilization of them.

Effect of ultraviolet on thiamine and thiamine disulfides

In a neutral medium, the exposure of thiamine disulfide to the ultraviolet of solar radiation (as well as to the ultraviolet radiation of mercury lamp with λ > 300 nm) results in the formation of a thiamine molecule with closed thiazole ring and a molecule of thiamine thiazolone. Asymmetric thiamine disulfides, e.g., thiamine propyl disulfide, on exposure to ultraviolet (UVA range) produced thiamine and propyl disulfides. Thiamine and thiazolone of thiamine are stable upon exposure to light of 320-400 nm (UVA range). UV irradiation within spectral range of 200-300 nm results in further photodestruction of thiamine and thiamine thiazolone and production of 2-methyl-4-amino-5aminomethyl-pyrimidine as the main photoproduct. The possibility to use thiamine disulfide derivatives as a promising class of anti-cataract drugs as well as drugs to decrease the toxic effect of ultraviolet radiation on human retina is discussed.

Development of an HPLC-UV Method to Assay Empagliflozin Tablets and Identification of the Major Photoproduct by Quadrupole Time-of-Flight Mass Spectrometry.

Diabetes is a set of metabolic disorders that affect >400 million individuals worldwide. Empagliflozin belongs to the gliflozin class and is used orally to treat type 2 diabetes. In this study, a simple stability-indicating HPLC-UV method was developed to assay empagliflozin tablets and its main photoproduct was identified by high-resolution mass spectrometry. The mobile phase, which was optimized by Central Composite Design, was composed of methanol, acetonitrile and purified water (60:5:35v/v), at a flow rate of 1mLmin-1. The calibration curve was linear in the range of 5-150μgmL-1. All the validation parameters were met and the method was specific, even in the presence of degradation products. In the forced degradation study, empagliflozin standard and empagliflozin tablets were submitted to several conditions (acidic, alkaline, neutral and oxidant media, thermal, photolytic and humidity), and empagliflozin showed instability under all these conditions. A degradation product generated after drug exposure to ultraviolet C radiation was isolated and analyzed by quadrupole time-of-flight mass spectrometry, and the results suggested that empagliflozin undergoes decomposition by a dechlorination pathway. In silico toxicity was predicted for the degradation product, which showed a high risk of genotoxicity and hepatotoxicity.

Исследование фототрансформации бисфенола А в воде в присутствии материалов на основе ультратонких полипропиленовых волокон

The effect of UV radiation on the efficiency phototransformation BPA in water in the presence of polypropylene nonwoven based on ultrafine fibers. The absorption and fluorescence spectra of the investigated substance with types of fibers of various properties were obtained. After excitation with an excilamp, the main photoproduct BPA fluoresces in the region of ~408 nm. With an increase in the irradiation time from 0 to 10 minutes, the fluorescence intensity of this photoproduct increases. The absorption and fluorescence spectra of cyclohexane containing desorbed compounds from the fiber surface indicate the adsorption of a photoproduct on its surface during UV irradiation.