Hydrolysis Studies of Chalcogenopyrylium Trimethine Dyes. 2. Chalcogen Atom Effects on the Rates of Hydrolysis of Chalcogenopyrylium Dyes

Young, Darrin J.; Serguievski, Petr; Detty, Michael R.

doi:10.1021/jo980742z

Cited by 9 publications

(12 citation statements)

References 18 publications

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“…For the chalcogenopyrylium dyes 1 that have been evaluated as sensitizers for PDT, 14a, the major metabolic pathway observed for loss of dye is hydrolysis. The addition of water or hydroxide to the chromophore results in a loss of the long-wavelength absorption. , Hydrolytic stability impacts the circulating lifetime of the sensitizer in biological systems, the lifetime of the sensitizer at the active site, formulations for delivery of the sensitizer, and the distribution of metabolites from the sensitizer found in vivo. The circulating half-life of 1a , which has photophysical properties that are optimal for PDT, 14a, is on the order of 20 min as determined with an in vivo spectrophotometer in BALB-c mice .…”

Section: Chemistrymentioning

confidence: 99%

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2,4,6-Triarylchalcogenopyrylium Dyes Related in Structure to the Antitumor Agent AA1 as in Vitro Sensitizers for the Photodynamic Therapy of Cancer

et al. 1999

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Cationic chalcogenopyrylium dyes 2-4 were synthesized in six steps from 4-(dimethylamino)phenylethyne (7), have absorption maxima in methanol of 594, 631, and 672 nm, respectively, and generate singlet oxygen with quantum yields [Phi((1)O(2))] of 0.020, 0.064, and 0.037, respectively. Dyes 2-4 are hydrolytically more stable than other chalcogenopyrylium dyes evaluated previously as sensitizers for photodynamic therapy. At 10 microM final concentration, all dyes 2-4 inhibited cytochrome c oxidase during irradiation of tumor mitochondrial suspensions treated with 10 microM dye. The degree of enzyme inhibition was abated in a reduced oxygen environment and in the presence of imidazole, a singlet oxygen trap. Superoxide dismutase, at a final concentration of 30 U, did not alter the photosensitized inhibition of mitochondrial cytochrome c oxidase by dyes 2-4. These data suggest that singlet oxygen may play a major role in the photosensitized inhibition of mitochondrial cytochrome c oxidase. Irradiation of R3230AC rat mammary adenocarcinoma cells in the presence of dyes 2-4 caused a significant loss in cell viability with thiopyrylium dye 2 displaying the greatest phototoxicity. Initial acute toxicity studies in vivo demonstrate that, at 10 mg/kg, none of the three dyes displayed overt toxicity.

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Section: Chemistrymentioning

confidence: 99%

“…The initial step in the hydrolysis of chalcogenopyrylium salts involves the addition of hydroxide/water to the ring . Addition can occur at the 2-, 4-, or 6-position of the ring, and the addition is reversible.…”

Section: Chemistrymentioning

confidence: 99%

2,4,6-Triarylchalcogenopyrylium Dyes Related in Structure to the Antitumor Agent AA1 as in Vitro Sensitizers for the Photodynamic Therapy of Cancer

et al. 1999

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“…1 while the addition of hydroxide leads directly to the intermediate alcohol. Any alcohol that is formed from dyes 1-3 has significantly decreased long-wavelength absorption compared to the starting dye, accompanied by an increase in absorption in the <500 nm region (16).…”

Section: Discussionmentioning

confidence: 99%

“…If the intermediate alcohol does not undergo an irreversible reaction, then the addition of water is reversible. Plots of log kob, versus pH for aqueous solutions of the dyes with reversible hydrolysis will have plateau regions (corresponding to regions where the dyes act as buffers) and the dyes will have pK, determined by the intersection of the slope for the rise to the plateau region with the slope of the plateau region (16,17). The plateau region is especially clear for dye 3 in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The pK, of dyes 2 and 3 are near the physiological pH range and the differences in pH between tumor and normal tissue should not lead to large differences in rates of hydrolysis. Beyond this buffering region and for dye 1 with irreversible hydrolysis products, one would expect the log koh, versus pH profiles to be a series of parallel lines with a slope of 1 at higher pH as kohr is dominated by the (khydroxlde[HO I} term (16,17). For dye 1, the log kohp versus pH profile gives a slope of 1 for pH 6-12.…”

Section: Discussionmentioning

confidence: 99%

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pH‐Dependent Chalcogenopyrylium Dyes as Potential Sensitizers for Photodynamic Therapy: Selective Retention in Tumors by Exploiting pH Differences between Tumor and Normal Tissue

Bellnier

Young

Detty

et al. 1999

Photochem & Photobiology

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Ideal photosensitizers have long-wavelength absorption and strong tumor selectivity with rapid clearance from normal tissues. The telluroselenopyrylium dye 1 that absorbs light at 795 nm (E = 285000 M-' cm-I) has a novel property that enhances the tumor specificity and normal tissue clearance. After intralesional injection to both tumors and surrounding skin, it disappeared from the normal skin of BALB/c mice faster than it did from subcutaneously implanted Colon 26 tumors, which resulted in therapeutic selectivity. In vivo reflectance spectroscopy showed that the half-life in tumor was about 50 min while in skin it was around 12 min. This phenomenon appears to be related to the pH differences in normal skin versus tumor, because the rates of drug hydrolysis in solution were shown to be sensitive to changes in pH. Inhibition of tumor regrowth following intratumoral photosensitizer administration depended on both light dose and drug dose, as well as the time interval between dye injection and irradiation; selectivity depended on the time interval. Although treatment parameters were not optimized efficacy was superior to systemic Photofrine under our standard conditions. We discuss how new, more optimal, photosensitizers can be designed that use rates of hydrolysis to exploit the differences in pH between normal tissue and tumor.

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A Near‐IR Fluorimetric Chemosensing System for the Turn‐On Detection of Hydrogen Sulfate Anion

Teknikel

2024

ChemistrySelect

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We report a near‐IR fluorescence turn‐on chemosensing system for the selective detection of HSO4− anion in aqueous media. This system utilizes the equilibrium between the fluorescent pyrylium salt and its non‐fluorescent diketone form. The pyrylium compound we synthesized (λflo=674 nm) rapidly converts to its diketone form in the aqueous medium (ethanol‐water 4 : 1). HSO4− anion provides proton to diketone form inducing its conversion to pyrylium. Therefore, the sensor system responds to the presence of HSO4− by an increase in fluorescence. The change in the fluorescence increase is linear within the 20–55 μM range with a limit of detection of 12.8 μM. The system demonstrates high selectivity for HSO4− over other anions, as validated through fluorimetric titration studies. Additionally, interference studies highlight the minimal impact of common anions on bisulfate detection. Reversibility tests reveal the pronounced reversibility of the sensor system, with over 90 % recovery of fluorescence intensity achieved in subsequent iterations.

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Hydrolysis Studies of Chalcogenopyrylium Trimethine Dyes. 2. Chalcogen Atom Effects on the Rates of Hydrolysis of Chalcogenopyrylium Dyes

Cited by 9 publications

References 18 publications

2,4,6-Triarylchalcogenopyrylium Dyes Related in Structure to the Antitumor Agent AA1 as in Vitro Sensitizers for the Photodynamic Therapy of Cancer

2,4,6-Triarylchalcogenopyrylium Dyes Related in Structure to the Antitumor Agent AA1 as in Vitro Sensitizers for the Photodynamic Therapy of Cancer

pH‐Dependent Chalcogenopyrylium Dyes as Potential Sensitizers for Photodynamic Therapy: Selective Retention in Tumors by Exploiting pH Differences between Tumor and Normal Tissue

A Near‐IR Fluorimetric Chemosensing System for the Turn‐On Detection of Hydrogen Sulfate Anion

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