Papers by Vladimir Kuzmin
Technologies
Quantum yields (φT) and energies (ET) of the first triplet state T1 for four molecules of cyanine... more Quantum yields (φT) and energies (ET) of the first triplet state T1 for four molecules of cyanine dyes with two chromophores (BCDs), promising photoactive compounds for various applications, for example, as photosensitizers in photodynamic therapy (PDT) and fluorescence diagnostics (FD), were studied in 1-propanol solutions by steady-state and time-resolved optical absorption techniques. BCDs differ by the structure of the central heterocycle, connecting the chromophores. The heterocycle structure is responsible for electron tunneling between chromophores, for which efficiency can be characterized by splitting of the BCD triplet energy levels. It was shown that the increase in the tunneling efficiency reduces ET values and increases φT values. This aspect is very promising for the synthesis of new effective photosensitizers based on cyanine dyes with two interacting chromophores for various applications, including photodynamic therapy.
International Journal of Molecular Sciences
The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxyg... more The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasm...
Problems in oncology, 2018
Gold complexes (GC) reveal antitumor activity against xenografts of human tumors as well as again... more Gold complexes (GC) reveal antitumor activity against xenografts of human tumors as well as against transplantable animal tumors in vivo and demonstrate cytotoxic effect against the wide spectrum of human tumor cells in vitro. GC had been effective against tumors with the acquired resistance to the platinum compounds. It is revealed the strong difference between mechanism of action of GC and platinum derivatives. Proteins, mainly thioredoxin reductase and proteasoma 26S, are the principal targets for the GC action but not for the platinum derivatives impact. Thioredoxin reductase and proteasoma 26S activity inhibition by GC leads to the development of the apoptosis mainly by the mitochondrial way in tumor cells.
Tetrapyrrole-based compounds are widely used as photosensitizers (PS) for photodynamic therapy (P... more Tetrapyrrole-based compounds are widely used as photosensitizers (PS) for photodynamic therapy (PDT) of cancer and other disorders. A major requirement for a high efficacy of these compounds is their interaction with plasma proteins in the body, in particular, serum albumin (SA) and low-density lipoproteins (LDL). These interactions are critical for targeted delivery of PS to the site of the disease as well as for drug release and metabolism. Moreover, the microenvironment of the PS may strongly influence the formation of reactive oxygen species, the key mediators of PDT-induced tumor cell death.
Kinetics and Catalysis, 2011
The rate constants and activation parameters of the reactions of the carbocation resulting from 6... more The rate constants and activation parameters of the reactions of the carbocation resulting from 6-ethoxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline photolysis with methanol (k 1) and the methoxide ion (k 2) have been measured by flash photolysis in binary mixtures of methanol with inert solvents (nonpolar pentane and polar acetonitrile) in wide composition ranges. The changes in the activation parameters for k 1 at different
The Journal of Antibiotics, 2013
A series of olivomycin A derivatives containing different combinations of the acyl residues in th... more A series of olivomycin A derivatives containing different combinations of the acyl residues in the carbohydrate chains was obtained. The formation of complexes of Mg 2 þ-coordinated dimers of these compounds with double-stranded DNA was studied using spectral methods such as absorption, fluorescence and circular dichroism (CD) spectral analyses. There was a good correlation of the values of binding constants of complexes (antibiotic) 2 Mg 2 þ-DNA, the quantum yields of fluorescence and changes of the induced CD spectra with topoisomerase I inhibition and cytotoxicity. We demonstrate that the presence of the acyl groups in the saccharide residues of olivomycin A derivatives is absolutely necessary for a high cytotoxic potency of these antibiotics. On the basis of the experimental results and quantum chemical calculations, we presume that the acyl residue in the 4-O-position in the A-sugar residue is involved, to the most part, in the antibiotic-antibiotic interactions in the (olivomycin) 2 Mg 2 þ dimers, whereas the O-acyl group in E-olivomicose residue largely participates in the formation of the (olivomycin) 2 Mg 2 þ-DNA complexes.
The experimental solutions were prepared in phosphate buffer (pH7.3;7.5mM), using Milli-Q quality... more The experimental solutions were prepared in phosphate buffer (pH7.3;7.5mM), using Milli-Q quality water. Figure S1. Dynamic light scattering diagram of fresh prepared (CdSe/ZnS)-Cys 558 quantum dots (QD). Figure S2. Luminescence decay curve of freshly prepared (CdSe/ZnS)-Cys 558 QD solution; λex =480nm and λem =558nm. Figure S3. a Normalized optical absorption spectrum of non-protonated TPPS4 . Inset: Normalized optical absorption spectra of the TPPS4 Q-bands (black line) and "aged" QD (red line), and the fluorescence emission spectrum of non-protonated TPPS4 with maximum at 644nm (blue line), λex =515nm. b TPPS4 fluorescence decay kinetics at 650nm, λex =515nm. Figure S4. a Optical absorption spectra of the aged (CdSe/ZnS)-Cys 558 QD and TPPS4 mixture at different TPPS4 concentrations. Inset: Details of the absorption spectra in the region of the porphyrin Q-bands. b Optical absorption spectra just for TPPS4 in the mixture TPPS4 +QD. The final spectrum of each sample was ...
Journal of the American Chemical Society, 2007
Preparation of Radiolabeled DNA Duplexes. The modified or complementary oligonucleotide strands (... more Preparation of Radiolabeled DNA Duplexes. The modified or complementary oligonucleotide strands (~50 pmol) were labeled at their 5'-termini using OptiKinase (USB, Cleveland, OH) and [γ-32 P]ATP (Perkin Elmer Life and Analytical Sciences, Boston, MA) at 37 o C for 30 min. Labeling at the 3'-termini was achieved using terminal deoxynucleotidyl transferase (Fermentas Inc., Hanover, MD) and [α-32 P]ddATP (Amersham Bioscience Corp. Piscataway, NJ). The labeled samples were purified by polyacrylamide gel electrophoresis at 15 W for 3 h at 45-50 o C and exposed to Kodak X-OMAT AR film (Eastman Kodak Co., Rochester, NY); the required bands were cut out and soaked overnight in 0.4 ml of an elution buffer (0.5 M ammonium acetate, 0.01 M magnesium diacetate). The extracted samples were desalted with Bio-Spin 6 columns (Bio-RAD, Melville, NY). The samples used in the photocleavage experiments were prepared by mixing "cold" and radiolabeled strands to obtain ~ 110 µL of the oligonucleotide solutions with a final concentration of ~ 5 µM. The DNA duplexes were prepared by annealing the two strands in 20 mM phosphate buffer solution (pH 7) containing 0.1 M NaCl at 90 o C for 2 min, and then allowing the samples to cool slowly back to room temperature overnight. The irradiated samples were mixed with 100 µL of 1 M piperidine, heated at 90 o C for 30 min, vacuum dried, and the traces of piperidine were removed by repeated lyophilization (2 times in 30 µL of distilled water). The final samples in the loading buffer (95% formamide, 0.025% xylene cyanole, and 0.025% bromophenol blue in sterilized water) were assayed using a 20% denaturing acrylamide/bisacrylamide (19:1) gel containing 7 M urea on a 38×50 cm Sequi-Gen Cell (Bio-Rad, Melville, NY).
Chemical Physics Letters, 1994
... 42 (1982) 4875. [ 8 ] T. Meehan and K. Straub, Nature 277 (1979) 410. [91 SC Cheng, BD Hilton... more ... 42 (1982) 4875. [ 8 ] T. Meehan and K. Straub, Nature 277 (1979) 410. [91 SC Cheng, BD Hilton, JM Roman and A. Dipple, Chem. Res. Toxicol. 2 (1989) 334. ... Soc. 78 (1984) 271. [ 12 ] C. Doubleday Jr., NJ Turro and J: F. Wang, Accounts Chem. Res. 22 (1989) 199. ...
Russian Journal of Bioorganic Chemistry
The spectral characteristics of the photosensitizer pyropheophorbide a (PPP) complexes with its c... more The spectral characteristics of the photosensitizer pyropheophorbide a (PPP) complexes with its carriers, that is, serum albumin and low density lipoproteins, were investigated in aqueous solutions at pH 7.4 and 5.0. The acidic pH did not affect the quantitative parameters of PPP binding to lipoproteins, whereas the affinity to albumin decreased. Differential role of acidification in the binding of PPP to biomacromolecules should be considered in the design of PPP based drugs, given that pH is frequently lowered in the sites of the disease.
Eye (London, England), Jan 22, 2018
The aim of this work is the determination of quantitative diagnostic criteria based on the spectr... more The aim of this work is the determination of quantitative diagnostic criteria based on the spectral characteristics of fundus autofluorescence to detect early stages of degeneration in the retina and retinal pigment epithelium (RPE). RPE cell suspension samples were obtained from the cadaver eyes with and without signs of age-related macular degeneration (AMD). Fluorescence analysis at an excitation wavelength of 488 nm was performed. The fluorescence lifetimes of lipofuscin-granule fluorophores were measured by counting time-correlated photon method. Comparative analysis of fluorescence spectra of RPE cell suspensions from the cadaver eyes with and without signs of AMD showed a significant difference in fluorescence intensity at 530-580 nm in response to fluorescence excitation at 488 nm. It was notably higher in eyes with visual pathology than in normal eyes regardless of the age of the eye donor. Measurements of fluorescence lifetimes of lipofuscin fluorophores showed that the co...
Nanoscale research letters, Jan 5, 2018
Interaction between porphyrins and quantum dots (QD) via energy and/or charge transfer is usually... more Interaction between porphyrins and quantum dots (QD) via energy and/or charge transfer is usually accompanied by reduction of the QD luminescence intensity and lifetime. However, for CdSe/ZnS-Cys QD water solutions, kept at 276 K during 3 months (aged QD), the significant increase in the luminescence intensity at the addition of meso-tetrakis (p-sulfonato-phenyl) porphyrin (TPPS) has been observed in this study. Aggregation of QD during the storage provokes reduction in the quantum yield and lifetime of their luminescence. Using steady-state and time-resolved fluorescence techniques, we demonstrated that TPPSstimulated disaggregation of aged CdSe/ZnS-Cys QD in aqueous solutions, increasing the quantum yield of their luminescence, which finally reached that of the fresh-prepared QD. Disaggregation takes place due to increase in electrostatic repulsion between QD at their binding with negatively charged porphyrin molecules. Binding of just four porphyrin molecules per single QD was su...
International Journal of Photoenergy
Spectral and fluorescent properties of ketocyanine dyes (polyenic bis-ω,ω′-aminoketones) and cati... more Spectral and fluorescent properties of ketocyanine dyes (polyenic bis-ω,ω′-aminoketones) and cation-anionic polymethine dyes of various structures were studied. The symmetric ketocyanines were shown to have a long-wavelength absorption band bathochromically shifted in comparison with that of the asymmetric ketocyanines with the same total length of the polyenic chain. The nonlinear ketocyanines exhibit the additional short-wavelength band in their absorption spectra, which can be more intense than the longwavelength band. The absorption spectra of ion pairs of cation-anionic dyes with overlapping cation and anion bands contain a new intense short-wavelength band inactive in fluorescence excitation. These spectral peculiarities are explained on the basis of chromophore interaction model. It has also been shown that theT1levels of ketocyanine chromophores do not essentially interact with each other in a ketocyanine molecule in nonpolar solvents; in polar solvents this interaction beco...
Biochimica et biophysica acta, Apr 24, 2017
The study of Acridine Orange (AO) spectral characteristics and the quenching of its singlet and t... more The study of Acridine Orange (AO) spectral characteristics and the quenching of its singlet and triplet excited states by TEMPO radical at its binding to DNA in the function of the DNA concentration and in the absence and presence of NaCl is reported. The study was performed using steady-state and time resolved optical absorption and florescence, fluorescence correlation spectroscopy and resonant light scattering techniques. The presence of different species in equilibrium: AO monomers and aggregates bound to DNA, has been demonstrated, their relative content depending on the DNA and the AO concentrations. At high DNA concentration the AO monomers are protected against the contact with other molecules, thus reducing the AO excited state quenching. The addition of NaCl reduces the AO binding constant to DNA, thus reducing the AO and DNA aggregation. The interaction of AO with DNA is a complex process, including aggregation and disaggregation of both components. This modifies the AO e...
Marine pollution bulletin, Jan 15, 2016
The wintertime maritime traffic operations in the Gulf of Finland are managed through the Finnish... more The wintertime maritime traffic operations in the Gulf of Finland are managed through the Finnish-Swedish Winter Navigation System. This establishes the requirements and limitations for the vessels navigating when ice covers this area. During winter navigation in the Gulf of Finland, the largest risk stems from accidental ship collisions which may also trigger oil spills. In this article, a model for managing the risk of winter navigation operations is presented. The model analyses the probability of oil spills derived from collisions involving oil tanker vessels and other vessel types. The model structure is based on the steps provided in the Formal Safety Assessment (FSA) by the International Maritime Organization (IMO) and adapted into a Bayesian Network model. The results indicate that ship independent navigation and convoys are the operations with higher probability of oil spills. Minor spills are most probable, while major oil spills found very unlikely but possible.
Phys Lett B, 1983
ABSTRACT
The Journal of Physical Chemistry, 1981
The binding of the polynuclear aromatic dyes acridine orange (AO) and proflavin (PF) to DNA in aq... more The binding of the polynuclear aromatic dyes acridine orange (AO) and proflavin (PF) to DNA in aqueous phosphate buffer solution at 25 f 1 “C has been studied by measuring the properties of the triplet excited states of these dyes. The triplet lifetimes can be measured ...
Photodiagnosis and Photodynamic Therapy, 2011
Journal of Biochemical and Biophysical Methods
Triplet flash photolysis techniques, coupled with quenching of the triplets by molecular oxygen, ... more Triplet flash photolysis techniques, coupled with quenching of the triplets by molecular oxygen, are utilized as probes of the microenvironment of polycyclic aromatic molecules bound covalently and non-covalently to DNA. The triplet-oxygen quenching properties of the following adducts in aqueous solutions at 25 +/- 1 degrees C were investigated: covalent adducts derived from the reaction of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (BaPDE) and of (+/-)-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaPE) with DNA, and non-covalent intercalation complexes of acridine orange (AO) and DNA. In all cases the quenching follows the Stern-Volmer quenching law with a quenching constant of KTO2 approximately equal to 10(9) M-1 X S-1 for the covalent BaPDE-DNA and BaPE-DNA complexes in aqueous solution. This value of KTO2 is characteristic of free molecules (not bound to DNA) and indicates that the pyrene chromophore is totally accessible to oxygen, and is thus not located at an intercalation-type of binding site in these covalent adducts. In contrast, the AO-DNA complexes are characterized by values of KTO2 approximately equal to 10(8) M-1 X S-1 indicating that the intercalated AO molecules are about ten times less accessible to molecular oxygen than free AO molecules. The KTO2 values for the covalent BaPDE-DNA and BaPE-DNA adducts decrease when the DNA concentration is increased in the 1 X 10(-4)-3 X 10(-3) M range (expressed in nucleotide concentration). This effect is attributed to intermolecular DNA-DNA interactions in which segments of adjacent DNA molecules tend to cover the pyrene chromophores on other strands, thus decreasing their accessibility to oxygen. In contrast the values of KTO2 for the non-covalent AO-DNA intercalation complexes are independent of DNA concentration, as expected for interior binding sites.
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Papers by Vladimir Kuzmin