Mechanism and Solvent Dependence for Photoionization of Promazine and Chlorpromazine

García, Carmina Saldaña; Smith, Glenn A.; McGimpsey, W. Grant; Kochevar, Irene E.; Redmond, Robert W.

doi:10.1021/ja00149a010

Cited by 44 publications

(88 citation statements)

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“…27 Under strong irradiation conditions, the phenothiazine derivates in aqueous solution form oxidation products, even at low concentrations of drug. 28,29 In our case, we have observed that the degradation product shows a slight fluorescence band around 364 nm. The use of fresh and stirred solutions assures that its contribution to the overall PTZ fluorescence can be considered negligible at the experimental conditions.…”

Section: Photophysical Propertiessupporting

confidence: 53%

Complexation and Chiral Drug Recognition of an Amphiphilic Phenothiazine Derivative with β‐Cyclodextrin

Guerrero‐Martínez

Montoro

Viñas

et al. 2008

Journal of Pharmaceutical Sciences

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Section: Photophysical Propertiessupporting

confidence: 53%

Complexation and Chiral Drug Recognition of an Amphiphilic Phenothiazine Derivative with β‐Cyclodextrin

Guerrero‐Martínez

Montoro

Viñas

et al. 2008

Journal of Pharmaceutical Sciences

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“…As already reported for CPZ [30][31][32][33], laser flash experiments with these phenothiazines derivatives indicate the occurrence of monophotonic ionization of the substrate, even if a scarce contribution of a biphotonic pathway cannot be excluded, as suggested for CPZ by conventional flash photolysis [35] and the two-color, twopulse excitation method [36] described above.…”

Section: Photophysical Characteristics Of Phenothiazinessupporting

confidence: 61%

“…Motten et al [33], Buetner et al [34] and Hall et al [35] in contrast to the previous works proposed a wavelength-dependent photoionization of CPZ and promazine (PMZ) involving stepwise biphotonic photoionization through the triplet state at wavelength> 280 nm and monophotonic photoionization at wavelength <300 nm: this wavelength dependence suggest that the mechanism for cutaneous phototoxicity associated with clinical use of CPZ, which occur at solar wavelength >300 nm does not involve photoionization. More recently Garcia et al [36] in an elegant study using conditions where absorption by singlet or triplet excited states occur selectively have confirmed that photoionization occurs through biphotonic excitation for CPZ and PZ.…”

Section: Photophysical Characteristics Of Phenothiazinesmentioning

confidence: 93%

Photosensitization of Biomolecules by Phenothiazine Derivatives

Viola¹,

Dall’Acqua

2006

CDT

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It is well known that many drugs act as photosensitizers towards cells by interacting with various cellular components such as lipids, proteins and nucleic acids. The structural modifications of the cellular components may occur by direct interactions of the excited states (singlets or triplets) of the drugs with the biological substrate or indirectly, through reactive species of oxygen sensitised by the drug themselves. In particular, the phototoxic activity of various drugs correlated with their potential photomutagenic and photocarcinogenic effects, takes place through DNA modification. Phenothiazines, a class of antihistaminic (anti-H1) or neuroleptic drugs used in the therapy of mental illness, such as schizophrenia, organic psychoses and other mental disorders, are known to induce photosensitization of the skin by systemic use or by topical applications as antiallergic drugs. In this review we have focused our attention on the photosensitizing property of phenothiazines and related compounds both in vitro and in vivo systems. Particular attention has been given to the mechanism of photo reaction with biomolecules such as lipids, proteins and DNA. Moreover there is a growing interest in drugs having photobiological effects because of their possible application as phototherapeutics. It has been interesting in this context to mention briefly the possible application of phenothiazine derivatives as new photosensitizers for their therapeutic application in photodynamic therapy (PDT) or in the light inactivation of viruses and bacteria.

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“…The changes were perceived from indirect measurements that suggested the formation of radicals leading to the substitution at the sulfur atom (sulfoxides) and loss of the chloride at C-2 forming PZ. These changes were also perceived as “destruction” of the CPZ molecule, and the use of light to bring about this “destruction” was termed “photolysis” [27], [34], [35], [49]. Nevertheless, because the energy of a laser beam is thousands of times greater than that generated by UV light sources, we considered the possibility that lasers could be used to rapidly modify molecules with prolongation of exposure to hours rather than nanoseconds [32] and perhaps be used to produce reactions not possible with routine pyrogenic techniques used in organic chemistry.…”

Section: Discussionmentioning

confidence: 99%

“…In a reference paper, the interaction of some phenothiazines with laser beams, the mechanism for photoionization of promazine (PZ) and CPZ has been studied as a function of solvent and excitation conditions [35]. It was shown that sequential biphotonic absorption is responsible for photoionization induced by irradiation with pulsed laser beams at 308 or 355 nm and that photoionization is solvent dependent upon excitation of the triplet state at 355 nm or near its absorption maximum of 460 nm.…”

Section: Introductionmentioning

confidence: 99%

Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

et al. 2013

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IntroductionPhenothiazines when exposed to white light or to UV radiation undergo a variety of reactions that result in degradation of parental compound and formation of new species. This process is slow and may be sped up with exposure to high energy light such as that produced by a laser.MethodsVarying concentrations of Chlorpromazine Hydrochloride (CPZ) (2–20 mg/mL in distilled water) were exposed to 266 nm laser beam (time intervals: 1–24 hrs). At distinct intervals the irradiation products were evaluated by spectrophotometry between 200–1500 nm, Thin Layer Chromatography, High Pressure Liquid Chromatography (HPLC) - Diode Array Detection, HPLC tandem mass spectrometry, and for activity against the CPZ sensitive test organism Staphylococcus aureus ATCC 25923.ResultsCPZ exposure to 266 nm laser beam of given energy levels yielded species, whose number increased with duration of exposure. Although the major species produced were Promazine (PZ), hydroxypromazine or PZ sulfoxide, and CPZ sulfoxide, over 200 compounds were generated with exposure of 20 mg/mL of CPZ for 24 hrs. Evaluation of the irradiation products indicated that the bioactivity against the test organism increased despite the total disappearance of CPZ, that is due, most probably, to one or more new species that remain yet unidentified.ConclusionsExposure of CPZ to a high energy (6.5 mJ) 266 nm laser beam yields rapidly a large number of new and stable species. For biological grade phenothiazines (in other words knowing the impurities in the samples: solvent and solute) this process may be reproducible because one can control within reasonably low experimental errors: the concentration of the parent compound, the laser beam wavelength and average energy, as well as the duration of the exposure time. Because the process is “clean” and rapid, it may offer advantages over the pyrogenically based methods for the production of derivatives.

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Mechanism and Solvent Dependence for Photoionization of Promazine and Chlorpromazine

Cited by 44 publications

References 0 publications

Complexation and Chiral Drug Recognition of an Amphiphilic Phenothiazine Derivative with β‐Cyclodextrin

Complexation and Chiral Drug Recognition of an Amphiphilic Phenothiazine Derivative with β‐Cyclodextrin

Photosensitization of Biomolecules by Phenothiazine Derivatives

Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

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