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Biomedical subjects

Daniel E Falvey

Publications and source records attributed to Daniel E Falvey.

14 recordsLinked to original sources
PubMed2005

Photorelease of carboxylic and amino acids from N-methyl-4-picolinium esters by mediated electron transfer.

One electron reduction of N-alkyl-4-picolinium (NAP) esters initiates C-O bond scission releasing a carboxylate anion. Previous experiments have demonstrated that this process can be initiated by photoinduced electron transfer from an electron-donating sensitizer. In the present study it is demonstrated that a comparable photorelease process can be initiated by photolysis of an electron acceptor (mediator), which in turn abstracts an electron from a ground state electron donor. The resulting mediator anion radicals donate an electron to the NAP ester, triggering release of the carboxylate anion. It is demonstrated that when benzophenone is used as a mediator, higher quantum yields for ester decomposition can be achieved compared with sensitizers that do direct photoinduced electron transfer.

Amino Acids↗
PubMed2005

Diphenylnitrenium ion: cyclization, electron transfer, and polymerization reactions.

Reactions of diphenylnitrenium ion were examined using laser flash photolysis (LFP), product analysis, and computational modeling using density functional theory (DFT). In the absence of trapping agents, diphenylnitrenium ion cyclizes to form carbazole. On the basis of laser flash photolysis experiments and DFT calculations it is argued that this process is a concerted cyclization/proton transfer that forms the H-4a tautomer of carbazole. Additional LFP experiments and product studies show that diphenylnitrenium ion reacts with electron-rich arenes (e.g., N,N-dimethylaniline, diphenylamine, and carbazole) through an initial one-electron transfer. The radical intermediates formed in this step then couple to form dimeric products. Secondary reactions between the diphenylnitrenium ion and these dimers results in the formation of oligomeric materials.

Journal Article↗
PubMed2005

Photolytic release of carboxylic acids using linked donor-acceptor molecules: direct versus mediated photoinduced electron transfer to N-alkyl-4-picolinium esters.

[reaction: see text] Efficient photorelease (Phi = 0.7) of carboxylic acids is achieved with a covalently linked mediator (benzophenone) protecting group (N-alkyl-4-picolinium ester) molecule. The mechanism involves initial photoreduction of the mediator, followed by rapid electron transfer to the protecting group.

Journal Article↗
PubMed2005

Photorelease of carboxylic acids, amino acids, and phosphates from N-alkylpicolinium esters using photosensitization by high wavelength laser dyes.

Visible light (>450 nm) is used to efficiently cleave carboxylic acids, amino acids, and phosphates from their N-methyl picolinium esters. Photolysis using pyrromethene dyes PM 546 and PM 597 and also coumarin 6 as photosensitizers effects release of carboxylic acids, N-protected amino acids, and phosphates in quantitative yields. The effective rate of photorelease by the dyes, Phiepsilon, was found to be as high as 4500 M-1 cm-1. The photorelease proceeds through photoinduced electron transfer from the dye sensitizers to the N-methyl picolinium group. Fluorescence quenching and laser flash photolysis experiments support the photoinduced electron-transfer mechanism.

Amino Acids↗
PubMed2005

Photogenerated N-methyl-N-1-naphthylnitrenium ion: laser flash photolysis, trapping rates, and product study.

N-Methyl-N-1-naphthylnitrenium ion (2) was generated through photolysis of 1-(N-methyl-N-(1-naphthyl)amino)-2,4,6-trimethylpyridinium tetrafluoroborate (1). Laser flash photolysis (LFP) with time-resolved UV-vis (TRUV) detection as well as photoproduct analysis verified that the expected nitrenium ion was formed cleanly and rapidly following photolysis. Consistent with an earlier study, which used competitive trapping methods (Novak, M. et al. J. Org. Chem. 1999, 64, 6023-6031), it is found that 2 reacts rapidly with a variety of nucleophiles. The high reactivity of 2 relative to other arylnitrenium ions is discussed in terms of steric and electronic effects.

Journal Article↗
PubMed2004

C-O bond fragmentation of 4-picolyl- and N-methyl-4-picolinium esters triggered by photochemical electron transfer.

Photochemical reduction of several 4-picolyl- and N-methyl-4-picolinium esters was examined using product analysis, laser flash photolysis, and fluorescence quenching. It is demonstrated that the radical (anions) formed in these reactions readily fragment to yield a carboxylic acid and a 4-pyridylmethyl radical intermediate. The high chemical and quantum yields observed for these photoreactions suggests that these esters can be used as photolabile protecting groups.

Journal Article↗
PubMed2004

Effect of meta electron-donating groups on the electronic structure of substituted phenyl nitrenium ions.

Density functional theory (UB3LYP/6-31G(d,p)) was used to determine substituent effects on the singlet-triplet-state energy gap for 21 meta-substituted phenylnitrenium ions. It was found that strongly electron-donating substituents stabilize the triplet state relative to the singlet state. With sufficiently strong meta electron donors (e.g., m,m'-diaminophenylnitrenium ion) the triplet is predicted to be the ground state. Analysis of equilibrium geometries, Kohn-Sham orbital distributions, and Mulliken spin densities for the triplet states of this series of nitrenium ions leads to the conclusion that there are two spatially distinct types of low-energy triplet states. Simple arylnitrenium ions such as phenylnitrenium ions as well as those having electron-withdrawing or weakly donating meta substituents have lowest-energy triplet states that are n,pi in nature. That is, one singly occupied molecular orbital is orthogonal to the plane of the phenyl ring and one is coplanar. These n,pi triplets are generally characterized by large ArNH bond angles (ca. 130-132 degrees ) and an NH bond that is perpendicular to the plane of the phenyl ring. In contrast, meta donor arylnitrenium ions have a lowest-energy triplet state best described as pi,pi. That is, both singly occupied molecular orbitals are orthogonal to the aromatic ring. Such pi,pi states are characterized by NH bonds that are coplanar with the phenyl ring and have ArNH bond angles that are more acute (ca. 110-111 degrees ). These triplet nitrenium ions have electronic structures analogous to those of meta-benzoquinodimethane derivatives.

Journal Article↗
PubMed2004

Photoremovable protecting groups based on electron transfer chemistry.

Photoremovable protecting groups (also known as photolabile protecting groups, phototriggers, or caged molecules) are functional groups that are attached to a molecule in such a way as to render the latter inactive. Exposure to light releases the protecting group, restoring functionality to the molecule. The use of photoremovable protecting groups (PRPGs) allows for precise spatial and temporal control of chemical reactions. Such groups have found use in many diverse applications, ranging from time resolved studies of physiological processes, to fabrication of spatially resolved combinatorial libraries of DNA. Recent research efforts have focused on designing protecting groups that are removed through photoinduced electron transfer (PET), rather than by direct photolysis. The PET strategy allows the light absorption step to be decoupled from the bond breaking step, thus permitting more control over the wavelengths of light used in the release process. The application of these types of protecting groups to the photochemical release of amines, alcohols, ketones, and carboxylic acids is described.

Journal Article↗
PubMed2003

In vitro studies on the photobiological properties of aloe emodin and aloin A.

Plants containing aloin A, aloe emodin, and structurally related anthraquinones have long been used as traditional medicines and in the formulation of retail products such as laxatives, dietary supplements, and cosmetics. Since a recent study indicated that topically applied aloe emodin increases the sensitivity of skin to UV light, we examined the events following photoexcitation of aloin A and aloe emodin. We determined that incubation of human skin fibroblasts with 20 microM aloe emodin for 18 h followed by irradiation with UV or visible light resulted in significant photocytotoxicity. This photocytotoxicity was accompanied by oxidative damage in both cellular DNA and RNA. In contrast, no photocytotoxicity was observed following incubation with up to 500 microM aloin A and irradiation with UVA light. In an attempt to explain the different photobiological properties of aloin A and aloe emodin, laser flash photolysis experiments were performed. We determined that the triplet state of aloe emodin was readily formed following photoexcitation. However, no transient intermediates were formed following photoexcitation of aloin A. Therefore, generation of reactive oxygen species and oxidative damage after irradiation of aloin A is unlikely. Although aloin A was not directly photocytotoxic, we found that human skin fibroblasts can metabolize aloin A to aloe emodin.

Animals↗
PubMed2003

Photochemically generated arylnitrenium ions: substituent effects on reactivity studied by laser flash photolysis.

Laser flash photolysis is used to examine reaction rates of four arylnitrenium ions: N-methyl-N-(4-chlorophenyl)-, -(4-biphenylyl)-, -(4-methylphenyl)-, and -(4-methoxyphenyl)nitrenium ion. These intermediates are generated from photolysis of appropriately substituted N-aminopyridinium ions. Kinetic analysis of trapping rates shows that the nitrenium ions react with weak nucleophiles in the order 4-Cl approximately 4-Me > 4-Ph > 4-OMe. Generally, amines react with the arylnitrenium ions at or near the diffusion-limited rate. Only in cases where the least reactive nitrenium ion (4-OMe) reacts with sterically hindered amines is any deviation from this generalization observed. The addition of a 2-acetyl substituent to these structures produces an interesting effect. In the case of the 4-Cl and 4-Ph analogs, the electron-withdrawing acetyl group decreases the rate of nucleophilic addition, yet with the 4-OMe and 4-Me compounds, the acetyl group increases the rate of addition. These results are discussed in terms of competing electronic and steric effects.

Journal Article↗
PubMed2002

Reactions of N-methyl-N-(4-biphenylyl)nitrenium ion with electron-rich arenes: laser flash photolysis and product studies.

An arylnitrenium ion, N-methyl-N-(4-biphenylyl)nitrenium ion, was generated through photolysis of 1-(N-methyl-N-4-biphenylyl)amino-2,4,6-trimethylpyridinium tetrafluoroborate, and its reactions with various donor-substituted arenes (e.g., 1,3,5-trimethoxybenzene, mesitylene, 1,4-dimethoxybenzene, hexamethylbenzene, etc.) were examined using product analysis and laser flash photolysis. In general, trapping of the short-lived nitrenium ion by the arenes leads to three types of products: (1) the parent amine, N-methyl-N-4-biphenylylamine; (2) an ortho-adduct, where the ring position ortho to the nitrenium ion center is bonded to the arene ring; and (3) an N-adduct, where the nitrenium ion nitrogen is bonded to the trap. Laser flash photolysis studies show that the rates of these trapping reactions vary from 10(4) to 10(9) M(-1) s(-1), depending on the structure of the arene trap. These trapping rate constants do not correlate with the one-electron oxidation potential of the arene, nor with the expected stability of a sigma-complex derived from direct electrophilic aromatic substitution. It is argued that the observed rate constants correspond to initial formation of a pi-complex between the arylnitrenium ion and the arene trap. This complex then forms the observed products.

Journal Article↗
PubMed2002

Photoinduced electron transfer cleavage of oxetane adducts of uracil and cytosine.

Oxetane adducts of 1,3-dimethyluracil and 1,N4,N4-trimethylcytosine were prepared and their behavior under photoinduced electron transfer was examined by fluorescence quenching, laser flash photolysis and product analysis. The excited state electron donor, N,N,N',N'-tetramethylbenzidine, was shown to photosensitize a net cycloreversion of these oxetanes to give the pyrimidine derivative and benzophenone. It is demonstrated that this reaction occurs via the anion radical of the oxetane and that the latter cleaves very rapidly (>10(7) s(-1)).

Cytosine↗
PubMed2002

Photochemistry and phototoxicity of aloe emodin.

Photochemical pathways leading to the phototoxicity of the aloe vera constituent aloe emodin were studied. The results indicate a photochemical mechanism involving singlet oxygen to be the most likely pathway responsible for the observed phototoxicity. Aloe emodin was found to efficiently generate singlet oxygen when irradiated with UV light (phidelta = 0.56 in acetonitrile). The survival of human skin fibroblast cells in the presence of aloe emodin was found to decrease upon irradiation with UV light. A further decrease in cell survival was observed in D2O compared with H2O, suggesting the involvement of singlet oxygen as the primary pathway. Laser flash photolysis experiments were also carried out on aloe emodin alone and in the presence of various biological substrates. Aloe emodin proved to be relatively photostable (phi = 1 x 10(-4)) and a poor photo-oxidant (E*red = +1.02 V). Only absorption bands caused by the triplet state of aloe emodin (lambdamax = 480 nm) and the aloe emodin conjugate base (lambdamax = 520 nm) were observed in the transient spectra.

Anthraquinones↗