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Biomedical subjects

D G Whitten

Publications and source records attributed to D G Whitten.

At least 19 recordsLinked to original sources
PubMed2001

Building highly sensitive dye assemblies for biosensing from molecular building blocks.

Fluorescence superquenching is investigated for polyelectrolytes consisting of cyanine dye pendant polylysines ranging in number of polymer repeat units (N(PRU)) from 1 to 900, both in solution and after adsorption onto silica nanoparticles. As N(PRU) increases, the absorption and fluorescence evolve from monomer spectra to red-shifted features indicative of molecular J aggregates. In solution, the superquenching sensitivity toward an anionic electron acceptor increases by more than a millionfold over the N(PRU) range from 1 to 900. The dramatic increase is attributed to enhanced equilibrium constants for binding the quenchers, and the amplified quenching of a delocalized exciton of approximately 100 polymer repeat units. The self-assembly of monomer onto silica and clay nanoparticles leads to formation of J aggregates, and surface-activated superquenching enhanced 10,000x over the monomer in solution, indicating the formation of "self-assembled polymers" on the nanoparticle surface. Utilization of these self-assembled polymers as high-sensitivity biosensors is demonstrated.

Biosensing Techniques↗
PubMed1999

Highly sensitive biological and chemical sensors based on reversible fluorescence quenching in a conjugated polymer.

The fluorescence of a polyanionic conjugated polymer can be quenched by extremely low concentrations of cationic electron acceptors in aqueous solutions. We report a greater than million-fold amplification of the sensitivity to fluorescence quenching compared with corresponding "molecular excited states." Using a combination of steady-state and ultrafast spectroscopy, we have established that the dramatic quenching results from weak complex formation [polymer(-)/quencher(+)], followed by ultrafast electron transfer from excitations on the entire polymer chain to the quencher, with a time constant of 650 fs. Because of the weak complex formation, the quenching can be selectively reversed by using a quencher-recognition diad. We have constructed such a diad and demonstrate that the fluorescence is fully recovered on binding between the recognition site and a specific analyte protein. In both solutions and thin films, this reversible fluorescence quenching provides the basis for a new class of highly sensitive biological and chemical sensors.

Biosensing Techniques↗
PubMed1996

Photochemistry and photophysical properties of novel, unsymmetrically substituted metallophthalocyanines.

A series of novel, unsymmetrically substituted metallo-phthalocyanines was synthesized, along with their symmetrically substituted analogs, and the effects of structure and metal substitution on their photophysical and photoredox properties were investigated. The macrocycles were synthesized using a mixed-condensation method followed by chromatographic separation of the resulting soluble products. They possess a catechol "active site" and three tert-butyl groups for enhanced solubility. The ground- and excited-state photophysical properties of the free-base, Zn(II) and Pd(II) macrocycles were measured and compared with their symmetrically substituted (tetra[tert-butyl]) analogs. The efficiency with which these macrocycles sensitize the formation of singlet oxygen was determined and discussed in the context of the excited-state photophysical properties. Several examples of photoinduced electron transfer reactions with one- and two-electron acceptors are demonstrated and discussed. These soluble molecules can be tuned to optimize their photochemical and redox properties by varying the central metal, axial ligands and other substituents, thereby providing a series of molecules for the investigation of photodynamic therapy and photoinduced electron transfer mechanisms.

Indoles↗
PubMed1995

Photosensitization and tissue distribution studies of the picket fence porphyrin, 3,1-TPro, a candidate for photodynamic therapy.

From a structurally distinct set of o-substituted tetraphenylporphyrins, the picket fence porphyrin (PFP), 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin (3,1-TPro) has been selected as a potential candidate for use in the photodynamic therapy (PDT) of cancer. In this report, the time-dependent tissue distribution of 14C-labeled 3,1-TPro is described along with the results of various treatment regimens. The tissue distribution of radiolabeled 3,1-TPro is comparable to that of other porphyrin photosensitizers with the advantage of being most effective at 4 h and being cleared rapidly from most tissues. The results of the various treatment regimen experiments, as well as other studies, indicate that the 3,1-TPro mechanism of action is similar to that of other photosensitizers, but may include some minor differences. The conclusion is that 3,1-TPro and other PFP offer a class of effective photosensitizers that may be exploited for their structural versatility, straightforward synthesis leading to a compound of high purity and known structure, and stability (both in terms of shelf-life and in vivo metabolism) as potential candidates for PDT.

Animals↗
PubMed1991

Photosensitizing activities of picket fence porphyrins in vitro and in vivo.

A set of structurally distinct o-substituted tetraphenylporphyrins, the picket fence porphyrins, were evaluated for their ability to photosensitize tumor mitochondria in vitro, in vivo-in vitro, and tumor implants in situ. Differential photosensitized inactivation efficiencies toward mitochondrial enzymes in vitro are reported for the 12 compounds studied as a function of side chain length and isomer structure. Fluorescence studies in aqueous solution coupled with mitochondrial uptake studies indicate that the observed range of inactivation efficiencies are due to different inherent solubilization properties for the picket fence porphyrins. Studies with the most soluble compound, 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin, using an in vivo-in vitro protocol indicate that a more effective photosensitization can be obtained by using an interval of 4 h between photosensitizer administration and irradiation as compared to 24 h for Photofrin II. Irradiation of tumors in vivo 4 h following administration of 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin, resulted in a mean tumor doubling time more than eight times longer than that observed for untreated tumors. 31P NMR spectroscopy in situ indicated that photodynamic therapy using 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin induced a rapid and significant reduction in high energy phosphate metabolites.

Animals↗
PubMed1988

Picket-fence porphyrins as potential phototherapeutic agents.

The synthetic "picket fence" porphyrin, tetra(o-acetamidophenyl)porphine (TAc), as a biological photosensitizer has been evaluated both in vitro and in vivo in mitochondria from the R3230AC mammary tumor. Studies in vitro, consisting of incubation of mitochondria with TAc at a concentration of 4.0 micrograms/ml followed by photolysis, result in the inhibition of cytochrome c oxidase, proton translocating ATPase, succinate dehydrogenase, and malate dehydrogenase. The diminution in activity of the first three enzymes is approximately 2-fold greater than that seen with Photofrin II under the same conditions. Although TAc exists as four isolable atropisomers, no differences among these different forms were observed in their photosensitized inhibition of mitochondrial enzymes. Administration to tumor-bearing rats of TAc i.p. at a dose of 25 mg/kg did result in accumulation of porphyrin within the mitochondria of the R3230AC tumor as determined by subsequent irradiation of isolated mitochondria. The potential utility of TAc and related porphyrins in cancer phototherapy is discussed.

Animals↗
PubMed1988

Photochemical reactions of dyes and olefins in monolayer films and supported multilayers.

The studies cited in this paper demonstrate that the unique environment provided by L. B. films and supported multilayers can produce a variety of molecular effects on photochemical reactivity that can, in turn, result in films, interfaces or surfaces having macroscopic properties which can be modulated by light. Although these investigations have been focused on molecular reactivity in films and how it can be modified (or persist unchanged), the results suggest several possible technological applications which might result from investigations directed more closely to them.

Alkenes↗