Kinetic study of delta-Ala induced porphyrins in mice using photoacoustic and fluorescence spectroscopies

The production of delta-aminolevulinic acid (ALA)-induced porphyrins in mice skin and blood was studied by photoacoustic and fluorescence spectroscopies. Mice were intraperitoneally administered with 30 mg/kg of ALA. The abdominal skin was subsequently excised at specific times within an 8-h interval and its absorption spectrum obtained by photoacoustics. The highest porphyrins concentration in skin, determined from the optical absorption of the Soret band at 410 nm, was found to occur nearly 2 h after ALA administration, but a first peak was also observed at approximately 15 min. Our hypothesis that the first peak represents the porphyrins content in blood vessels within the skin, whereas the second peak corresponds to porphyrins production in skin tissue, was confirmed by analysing the evolution of protoporphyrin IX content in plasma extracted intracardiacally. By finally applying phase resolved photoacoustic spectroscopy, we were able to evaluate the mean depth at which porphyrins are generated.     

Synthesis of 4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrospiro(benzo[h]quinazoline-5,1′-cyclohexane and its reaction with dibromoalkanes

4-(N-Benzoylthioureido)-3-ethoxycarbonyl-1,2-dihydrospiro(naphthalene-2,1-cyclohexane), which was synthesized from 4-amino-3-ethoxycarbonyl-1,2-dihydrospiro(naphthalene-2,1-cyclohexane) and benzoyl isothiocyanate, cyclized to give 4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrospiro(benzo[h]quinazoline-5,1-cyclohexane). Reaction of the latter with 1,2-dibromoethane or 1,3-dibromopropane gave products of intramolecular dialkylation at the S and N₍₃₎ atoms.A. L. Mndzhoyan Institute of Fine Organic Chemistry, Armenian National Academy of Sciences, Erevan 375014, Armenia. Center for the Investigation of Molecular Structure, Armenian National Academy of Sciences, Erevan 375014, Armenia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, 105–109, January, 1999.     

Synthesis of spiro(benzo[h]quinazoline-5,1′-cyclohexane) derivatives

3-p-Methoxyphenyl-4-oxo-2-mercapto-3, 4, 5, 6-tetrahydrospiro(benzo[h]quinazoline-4,1 -cyclohexane) wassynthesized by the reaction of 4-amino-3-ethoxycarbonvl-1, 2-dihydrospiro(naphthalene-2,1 '-cyclohexane) (1) with p-methoxyphenvl isothiocyanate without separation of the thioureido derivative. Amino ester 1 is transformed byacetamide and formamideinto 2-methyl-4-oxo-3, 4, 5, 6-tetrahydrospiro(benzo[h]quinazoline-5,1 -cyclohexane) and 4-oxo-3, 4, 5, 6-tetrahydrospiro(benzo[h]quinazoline-5,1-cyclohexane (11), respectively. Alkylation of quinazoline 11 with methyl iodide results in formation of 3-methyl-4-oxo-3, 4, 5, 6-tetrahydro-spiro (benzo[h]quinazoline-5,1 -cyclohexane). Amino ester 1 reacts with caprolactam with formation of 2, 3 pentamethylene-4-oxo-3, 4, 5, 6-tetrahydrospiro(benzo[h]quinazoline-5,1-cyclohexane). 4-Ethoxymethyleneamino-3-ethoxy-carbonyl-1,2-dihydrospiro(naphthalene-2,1-cyclohexane) was synthesized by the reaction of amino ester 1 with o-formic ester, and was converted into 3-amino-4-oxo-3, 4,5, 6-tetrahydro-spiro(benzo[h]quinazoline-5,1-cyclohexane) (VIII) by hydrazine hydrate. Aminoquinazoline VIII is acylated by acid chlorides with formation of 3-acylamino-4-oxo-3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1-cyclohexanes) and forms 3-benzyl-ideneamino-4-oxo-3,4,5,6-teirahydrospiro(benzo[h]quinazoline-5,1-cyclohexane) with benzaldehyde.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 530–533, April, 1996     

Synthesis and structure of 2-methyl-6-oxo-7,8-dihydrospiro(benzo[h]-triazolo[3,4-b]quinazoline-7,1′-cyclopentane)

The reaction of 4-amino-3-ethoxycarbonyl-1,2-dihydrospiro(naphthalene-2,1-cyclopentane) with benzoyl isothiocyanate led to the corresponding 4-(N-benzoylthioureido) derivative, the cyclization of which gave 4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrospiro(benzo[h]qquinazoline-5,1-cyclopentane). Condensation of the latter with hydrazine hydrate gave 2-hydrazino-3,4,5,6-tetrahydrospiro(benzo[h] quinazoline-5,1-cyclopentane), which formed 6-oxo-1H-7,8-dihydrospiro(benzo[h] triazolo[3,4-b] quinazoline7,1-cyclopentane) in reaction with orthoformice ester. Methylation of the product with methyl iodide led to its 2-methyl derivative.Communication 1, see ref. [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 658–662, May, 2000.     

Facile coupling of 2‐(1‐ethylthioethenyl)pyrroles with amines: A route to 2‐(1‐aminoethenyl)pyrroles and 1‐amino‐3‐iminopyrrolizines

2‐(2‐Cyano‐1‐ethylthioethenyl)pyrroles are readily coupled (50–55°) with primary and secondary amines at the position 1 of the ethenyl moiety to eliminate ethanethiol and afford 2‐(1‐amino‐2‐cyanoethenyl)pyrroles and/or their cyclic isomers ‐ functionalized 1‐amino‐3‐iminopyrrolizines in good to high yields.     

Dye-exchange dynamics in micellar solutions studied by fluorescence correlation spectroscopy

We investigated the dye-exchange dynamics between rhodamine 123 (R123), a mitochondrial fluorescent dye, and micelles as membrane mimetic systems. In the presence of neutral micelles (Triton X-100 and Brij 35) R123 partitions between the aqueous solution and the micellar pseudo-phase, undergoing red shift of the absorption and the emission spectra. Fluorescence correlation spectroscopy (FCS) was used to study the dynamics of these systems over an extremely wide time range and at the single-molecule level, yielding information in one and the same experiment about the diffusional dynamics of free and bound rhodamine and about the dye-exchange dynamics as well as several photophysical properties of the rhodamine bound to the micelles. It was found that the entry rate constants are diffusion-controlled, indicating that there are no geometric or orientational requirements for the association of the dye with the micelle. With respect to the dye-exchange dynamics, micelles are found to behave as soft supramolecular cages in contrast to other rigid supramolecular cavities, such as cyclodextrins. The exit rate constants depend on the surfactant and determine the stability of the binding. Single-molecule multiparameter fluorescence detection (MFD) was used to examine the fluorescence properties of individual molecules in comparison to ensembles of molecules. The MFD histograms confirm the fast dye-exchange dynamics observed by FCS and yield mean values of fluorescence lifetimes and anisotropies in agreement with those obtained in bulk measurements.