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Sergei A Vinogradov

Publications and source records attributed to Sergei A Vinogradov.

At least 19 recordsLinked to original sources
PubMed2006

Tomographic imaging of oxygen by phosphorescence lifetime.

Imaging of oxygen in tissue in three dimensions can be accomplished by using the phosphorescence quenching method in combination with diffuse optical tomography. We experimentally demonstrate the feasibility of tomographic imaging of oxygen by phosphorescence lifetime. Hypoxic phantoms were immersed in a cylinder with scattering solution equilibrated with air. The phantoms and the medium inside the cylinder contained near-infrared phosphorescent probe(s). Phosphorescence at multiple boundary sites was registered in the time domain at different delays (t(d)) following the excitation pulse. The duration of the excitation pulse (t(p)) was regulated to optimize the contrast in the images. The reconstructed integral intensity images, corresponding to delays t(d), were fitted exponentially to give the phosphorescence lifetime image, which was converted into the three-dimensional image of oxygen concentrations in the volume. The time-independent diffusion equation and the finite element method were used to model the light transport in the medium. The inverse problem was solved by the recursive maximum entropy method. We provide what we believe to be the first example of oxygen imaging in three dimensions using long-lived phosphorescent probes and establish the potential of these probes for diffuse optical tomography.

Computer Simulation↗
PubMed2006

Simultaneous fluorometry and phosphorometry of Langendorff perfused rat heart: ex vivo animal studies.

Fluorescence imaging of intrinsic fluorophores of tissue is a powerful method to assess metabolic changes at the cellular and intracellular levels. At the same time, exogenous phosphorescent probes can be used to accurately measure intravascular tissue oxygenation. Heart failure is the leading cause of death in America. A rat heart can potentially model the human heart to study failures or other abnormalities optically. We report simultaneous fluorescence and phosphorescence measurements performed on a rat heart. We have used two different optical systems to acquire fluorescence signals of flavoprotein and nicotinamide adenine dinucleotide--the two intrinsic fluorophores of mitochondria--and the phosphorescence signal of an intravascular oxygen probe to extract intracellular and intravascular metabolism loads, respectively.

Animals↗
PubMed2006

Oxygen pressures in the interstitial space and their relationship to those in the blood plasma in resting skeletal muscle.

This study compared oxygen pressures (Po(2)), measured by oxygen-dependent quenching of phosphorescence, in the intravascular (blood plasma) space in the muscle with those in the interstitial (pericellular) space. Our hypothesis was that the capillary wall would not significantly impede oxygen diffusion from the blood plasma to the pericellular space. A new near-infrared oxygen sensitive probe, Oxyphor G3, was used to obtain oxygen distributions in the interstitial space. Oxyphor G3 is a Pd-tetrabenzoporphyrin encapsulated inside generation 2 poly-arylglycine (AG) dendrimer. The periphery of the dendrimer is modified with oligoethylene glycol residues (average molecular weight 350) to make the probe water soluble and biologically inert. Oxyphor G3 was injected into thigh muscle using a 30-gauge needle. Histograms of the Po(2) in the interstitial space were measured in awake and anesthetized animals and compared with those for Oxyphor G2 in the intravascular (blood plasma) space. For awake mice, the lowest 10% of Po(2) values for the interstitial and intravascular spaces (believed to represent capillary bed) were not significantly different [23.8 (SD 4.5) and 25 Torr (SD 4.3), respectively], whereas, in isoflurane-anesthetized mice, there was a small but significant (P = 0.01) difference [20.4 (SD 6.3) and 27.9 Torr (SD 3.5), respectively]. The peak values for the histograms for the interstitial space in awake and isoflurane-anesthetized mice were 40.8 (SD 7.5) and 36.9 Torr (SD 8.3), respectively, whereas those for the intravascular space were 52.2 (SD 4.9) and 55.9 Torr (SD 8.4), respectively, showing no significant difference due to isoflurane anesthesia. The histograms for the intravascular space were significantly wider, with more contribution at higher Po(2) values. A different anesthetic, ketamine plus xylazine injected intraperitoneally, caused a marked decrease in the tissue Po(2) values in both spaces, with the time course and extent of the decrease dependent on the time after injection and variable among mice. It was, therefore, not further used.

Animals↗
PubMed2006

Feasibility of diffuse optical imaging with long-lived luminescent probes.

Long-lived near-infrared phosphors with high quantum yields have recently become available, making it possible to image oxygen distributions in tissue in three dimensions. By numerical simulations we demonstrate that, by using phosphorescent probes with appropriate oxygen quenching constants, one can image hypoxic phantoms in scattering media with adequate spatial resolution, employing simple time-gated measurements. The approach developed will guide experimental imaging of phosphorescence lifetime and oxygen pressure in living tissue.

Cell Hypoxia↗
PubMed2005

Synthesis and luminescence of soluble meso-unsubstituted tetrabenzo- and tetranaphtho[2,3]porphyrins.

[Structure: see text]. Syntheses of soluble tetrabenzoporphyrins (TBP) and tetranaphtho[2,3]porphyrins (TNP), with multiple substituents in the conjugated aromatic rings but bearing no substituents in the meso-positions, is reported. Both types of porphyrins were obtained by direct aromatization of precursor porphyrins, annealed with either cyclohexene or dihydronaphthalene fragments. TBPs and TNPs possess powerful absorption bands in the near-infrared (lambda = 610-710 nm, epsilon = 100,000-300,000 M(-1) cm(-1)) and exhibit strong luminescence. Free bases and Zn complexes fluoresce with quantum yields of up to 50%, whereas Pd and Pt complexes phosphoresce in solutions at ambient temperatures. Remarkably, the phosphorescence quantum yields of Pd and Pt TBPs reach as high as 20-50%, which places them among the brightest near-infrared phosphors known to date.

Luminescence↗
PubMed2005

Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging.

Maps of the oxygen distribution in the retina of the mouse eye were obtained by phosphorescence-lifetime imaging. Phosphor dissolved in the blood was excited by modulated light and phosphorescence imaged through microscope optics with an intensified-CCD camera. Phosphorescence lifetimes and oxygen pressures were calculated for each pixel of the images. The resolution was sufficient to permit the detection of anomalies that result in reduced oxygen pressures in individual retinal capillaries. High-resolution maps of oxygen distribution in the retina can provide greater understanding of the role of oxygen and vascular function in diseases of the eye.

Animals↗
PubMed2005

Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing antenna.

Imaging oxygen in 3D with submicron spatial resolution can be made possible by combining phosphorescence quenching technique with multiphoton laser scanning microscopy. Because Pt and Pd porphyrin-based phosphorescent dyes, traditionally used as phosphors in biological oxygen measurements, exhibit extremely low two-photon absorption (2PA) cross-sections, we designed a nanosensor for oxygen, in which a 2P absorbing antenna is coupled to a metalloporphyrin core via intramolecular energy transfer (ET) with the purpose of amplifying the 2PA induced phosphorescence of the metalloporphyrin. The central component of the device is a polyfunctionalized Pt porphyrin, whose triplet state emission at ambient temperatures is strong, occurs in the near infrared and is sensitive to O2. The 2PA chromophores are chosen in such a way that their absorption is maximal in the near infrared (NIR) window of tissue (e.g., 700-900 nm), while their fluorescence is overlapped with the absorption band(s) of the core metalloporphyrin, ensuring an efficient antenna-core resonance ET. The metalloporphyrin-antenna construct is embedded inside the protecting dendritic jacket, which isolates the core from interactions with biological macromolecules, controls diffusion of oxygen and makes the entire sensor water-soluble. Several Pt porphyrin-coumarin based sensors were synthesized and their photophyics studied to evaluate the proposed design.

Absorption↗
PubMed2005

Synthesis of symmetrical tetraaryltetranaphtho[2,3]porphyrins.

A new method of synthesis of meso-tetraaryltetranaphtho[2,3]porphyrins (Ar4TNP) has been developed. Ar4TNPs with peripheral functional groups are obtained by oxidative aromatization of meso-tetraarylporphyrins in which pyrrole units are fused with either octahydro- or dihydronaphthalene moieties. These precursor porphyrins are synthesized in four to five steps from readily available starting materials, such as naphthalene or 1,4-benzoquinone. The pathway originating in dihydronaphthalene, i.e., the "dialine" route, was found to be superior to the alternative "octaline"route in that it (1) enables the shortening of the overall reaction sequence, (2) has a broader scope in terms of the peripheral substitution in Ar4TNPs, and (3) affords higher yields of the target porphyrins. Pd complexes of the synthesized Ar4TNPs exhibit remarkably strong absorption bands at 710-720 nm (epsilon approximately 200,000 M(-1) cm(-1)) and phosphoresce at room temperature with moderate quantum yields (phi = 2-3%, lambda(max) = 900-1000 nm). The absorption maxima of naphthoporphyrins substituted with eight methoxy groups (Ar4TNP(OMe)8) were found to be about 15-20 nm red shifted compared to the corresponding maxima of unsubstituted Ar4TNPs. The X-ray crystallographic data suggest that these spectral shifts are caused not by the differences in nonplanar distortions of the macrocycles but by the purely electronic effects of the substituents.

Chemistry, Organic↗
PubMed2005

Arylamide dendrimers with flexible linkers via haloacyl halide method.

[reaction: see text] Soluble arylamide dendrons with flexible linkers, peripheral ester or carboxyl groups (R), and focal amino or halogen functionalities (F) were synthesized from aryl glycineamide (AG) building blocks. The AG blocks were prepared in high yields from trivial starting materials by Fischer's haloacyl halide method, which also could be extended to the dendrimer synthesis itself. The G2 AG dendrons were coupled to a Pd porphyrin core, demonstrating outstanding encapsulation efficiency in aqueous solutions.

Glycine↗
PubMed2005

Imaging oxygen pressure in the retina of the mouse eye.

The phosphorescence lifetime imaging system previously used to image oxygen in the retina of the cat eye was modified to allow imaging of phosphorescence lifetimes in the much smaller mouse eye. Following the lead of Shonat and coworkers, a frequency domain approach was used in which the excitation light source was modulated in a 50% on: 50% off square wave while the gate of the intensified CCD camera was similarly modulated but delayed with respect to the excitation. These were analyzed by fitting the intensity at each pixel to a sinusoid. The phase of the phosphorescence relative to the excitation was determined and from the phase shift and frequency, the phosphorescence lifetime was calculated. The Stern-Volmer relationship was then used to calculate the oxygen pressure at each pixel of the image array. High resolution maps of phosphorescence lifetime and oxygen pressure in the retina of the mouse eye have been attained. The retinal veins draining into the optic head appear as large, highly phosphorescent vessels against a lower phosphorescence background with a network of smaller vessels. The oxygen pressure in the retinal veins is typically from 20 to 30 mm Hg while the background has somewhat higher oxygen pressures. Experiments are underway to resolve the oxygen in the choroid from that in the retina. The arteries on the retinal surface can be observed, but their small diameter, relatively high oxygen pressures (> 90 mm Hg), and surrounding tissue with much lower oxygen pressures, makes accurate determination of the oxygen pressure a challenge.

Animals↗
PubMed2004

Oxygen distribution in murine tumors: characterization using oxygen-dependent quenching of phosphorescence.

In the present work, a novel method for detecting hypoxia in tumors, phosphorescence quenching, was used to evaluate tissue and tumor oxygenation. This technique is based on the concept that phosphorescence lifetime and intensity are inversely proportional to the oxygen concentration in the tissue sample. We used the phosphor Oxyphor G2 to evaluate the oxygen profiles in three murine tumor models: K1735 malignant melanoma, RENCA renal cell carcinoma, and Lewis lung carcinoma. Oxygen measurements were obtained both as histograms of oxygen distribution within the sample and as an average oxygen pressure within the tissue sampled; the latter allowing real-time oxygen monitoring. Each of the tumor types examined had a characteristic and consistent oxygen profile. K1735 tumors were all well oxygenated, with a peak oxygen pressure of 37.8 +/- 5.1 Torr; RENCA tumors had intermediate oxygen pressures, with a peak oxygen pressure of 24.8 +/- 17.9 Torr; and LLC tumors were all severely hypoxic, with a peak oxygen pressure of 1.8 +/- 1.1 Torr. These results correlated well with measurements of tumor cell oxygenation measured by nitroimidazole (EF5) binding and were consistent with assessments of tumor blood flow by contrast enhanced ultrasound and tumor histology. The results show that phosphorescence quenching is a reliable, reproducible, and noninvasive method capable of providing real-time determination of oxygen concentrations within tumors.

Animals↗
PubMed2004

Self-assembly of amphiphilic dendritic dipeptides into helical pores.

Natural pore-forming proteins act as viral helical coats and transmembrane channels, exhibit antibacterial activity and are used in synthetic systems, such as for reversible encapsulation or stochastic sensing. These diverse functions are intimately linked to protein structure. The close link between protein structure and protein function makes the design of synthetic mimics a formidable challenge, given that structure formation needs to be carefully controlled on all hierarchy levels, in solution and in the bulk. In fact, with few exceptions, synthetic pore structures capable of assembling into periodically ordered assemblies that are stable in solution and in the solid state have not yet been realized. In the case of dendrimers, covalent and non-covalent coating and assembly of a range of different structures has only yielded closed columns. Here we describe a library of amphiphilic dendritic dipeptides that self-assemble in solution and in bulk through a complex recognition process into helical pores. We find that the molecular recognition and self-assembly process is sufficiently robust to tolerate a range of modifications to the amphiphile structure, while preliminary proton transport measurements establish that the pores are functional. We expect that this class of self-assembling dendrimers will allow the design of a variety of biologically inspired systems with functional properties arising from their porous structure.

Biological Transport↗
PubMed2004

Novel versatile synthesis of substituted tetrabenzoporphyrins.

A novel general synthetic route to tetraaryltetrabenzoporphyrins (Ar(4)TBP) with various peripheral functional groups is developed. The procedure includes (i) Barton-Zard condensation of 1-nitro- or 1-phenylsulfonylcyclohexenes with isocyanoacetic acid esters, (ii) condensation of the resulting 4,5,6,7-tetrahydroisoindoles with aromatic aldehydes to give fused tetraaryltetracylohexenoporphyrins (Ar(4)TCHP), and (iii) aromatization of the metal complexes of Ar(4)TCHP's into the corresponding Ar(4)TBP's. Cu and Zn complexes of Ar(4)TBP's are further demetalated to give the corresponding Ar(4)TBP free bases. The overall yields for the sequence range from 15% to 40%, making the method suitable for the preparation of gram quantities of Ar(4)TBP's in a single run. The scope of the method, the selection of the peripheral substituents, the choice of the metal ions, and their influence on the yields of aromatization are discussed. The basic spectroscopic properties of newly synthesized Ar(4)TBP's and Ar(4)TCHP's are reported together with the first X-ray crystallographic structure of the NiAr(4)TBP complex.

Porphyrins↗
PubMed2004

Phosphorescence lifetime imaging in turbid media: the inverse problem and experimental image reconstruction.

Three-dimensional phosphorescence lifetime imaging is a novel method for the mapping of oxygen concentration in biological tissues. We present reconstruction techniques for recovering phosphorescent objects in highly scattering media based on the telegraph equation and two regularization methods, i.e., the Tikhonov-Phillips regularization and the maximum entropy method. Theoretical results are experimentally validated, and the reconstructed images of phosphorescent objects rendering oxygen maps in a layer are presented.

Biological Phenomena↗
PubMed2003

Novel route to functionalized tetraaryltetra[2,3]naphthaloporphyrins via oxidative aromatization.

A novel general route to substituted meso-tetraaryltetra[2,3]naphthaloporphyrins (Ar(4)TNP) and meso-tetraaryloctamethoxytetra[2,3]naphthaloporphyrins (Ar(4)(MeO)(8)TNP) via oxidative aromatization of nonaromatically fused porphyrin precursors is described. Ar(4)(MeO)(8)TNPs exhibit more red-shifted absorption bands than Ar(4)TNPs and differ dramatically in solubility. The first X-ray crystallographic structure of tetranaphthaloporphyrin, i.e., PdAr(4)TNP (Ar = 4-MeO(2)CC(6)H(4)), revealed that the degree of nonplanar distortion of this macrocycle is only slightly higher than that of the homologous tetrabenzoporphyrins (Ar(4)TBP).

Journal Article↗
PubMed2003

Luminescent Zn and Pd tetranaphthaloporphyrins.

Zn and Pd complexes of meso-tetraphenyltetranaphthaloporphyrins (Ph(4)TNP) exhibit strong infrared absorption bands and luminesce in solutions at room temperature. S1 --> S0 fluorescence (lambda(max) = 732 nm, phi = 5.3%) is the predominant emission in the case of ZnPh(4)TNP (1). This emission is in part due to the delayed fluorescence (phi = 1.1%). Phosphorescence (T1 --> S0) of 1 (lambda(max) = 973 nm) is very weak (phi = 0.04%) and occurs with lifetime of about 440 micros in deoxygenated DMF. In the case of PdPh(4)TNP (2), almost no S1 --> S0 fluorescence could be observed, while the main emission detected was T1 --> S0 phosphorescence (lambda(max) = 938 nm). The phosphorescence of 2 occurs with lifetime of about 65 micros and (phi=6.5%) in deoxygenated DMF solution. Metalloporphyrins 1 and 2 are promising near infrared dyes biomedical applications.

Fluorescent Dyes↗