- Primary processes of the electronic excited states of trans-urocanic acid
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The primary photoreactivity of the excited states of trans-urocanic acid (t-UA) is investigated by ultrafast transient-absorption spectroscopy. Fundamentally different photophysics were observed when t-UA is excited at 266 nm, near the peak of the absorption spectrum, and 306 nm, in the red tail of the absorption spectrum. The data support the conclusion that the wavelength-dependent photophysics of t-UA is due to the presence of two different closely spaced electronic states. Excitation at 266 nm populates a ππ* state that is localized on the imidazole ring. The transient data following photoexcitation of t-UA at 266 nm in both a pH 5.6 and a pH 7.2 solution are similar, even though the protonation state of the tertiary nitrogen on the imidazole ring is different at these two pH values. The data therefore support that the photophysics at pH 5.6 and pH 7.2 must involve a common excited state. Steady-state excitation spectra suggest that a proton transfer process from t-UA to the solvent occurs following the excitation at 266 nm at pH 5.6, which generates an electronically excited singlet state of the deprotonated molecule. This state is directly accessed by the 266 nm excitation of t-UA at pH 7.2. The population in this singlet state decays by intersystem crossing with a rate constant of 1.4 × 1011 s-1. Isomerization is not believed to occur from this triplet state. Excitation of t-UA at 306 nm populates an entirely different state, which leads to isomerization. From the observed ground state repopulation dynamics, the minimum rate for the excited state isomerization is 1.2 × 1010 s-1.
- Li,Hanson,Simon
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- Laser-induced in vitro isomerization of urocanic acid in UVA region and the origin of excited triplet state
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We demonstrate here unambiguously that (E)-urocanic acid, an epidermal and photobiologically important chromophore, undergoes isomerization to the (Z) isomer upon excitation with UVA (320-400 nm) light using monochromatic 355 and 340 nm laser radiation. Additionally, chemical evidence is presented that supports the isomerization coming from the excited singlet state, thus proving unequivocally that the previously observed triplet state is populated from the excited singlet manifold via intersystem crossing rather a weak S0→T1 transition.
- Mohammad, Taj
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- cis-Urocanic acid induces mast cell degranulation and release of preformed TNF-α: A possible mechanism linking UVB and cis-urocanic acid to immunosuppression of contact hypersensitivity
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The search for effective inhibitors of transdermal drug-induced contact sensitization was directed to dermal mast-cell-degranulating agents (MCDA). Human skin organ cultures were employed to test whether cis-urocanic acid (C-UA) and other potential MCDAs cause mast cell degranulation. These were then tested for their ability to inhibit the induction phase of the contact hypersensitivity reaction (CHR). C-UA at 1 μg/ml significantly depleted mast cell chymase, whereas trans-urocanic acid (T-UA) was relatively ineffective. C-UA, but not T-UA, induced local effects of liberated mast cell TNF-α, as detected by E-selectin expression on the micro-vascular dermal endothelium. C-UA significantly reduced (> 70%) the ear swelling response in Balb/c mice, when applied 24 h prior to application of a sensitizing amount of dinitrochlorobenzene (DNCB), and induced a prolonged (> 3 weeks) state of immune tolerance (> 40%). Similar effects on local immunosuppression of CHR were observed with topical chloroquine and capsaicin, while cromolyn, a mast cell membrane stabilizer, was unable to inhibit DNCB-induced CHR. It is suggested that MCDAs may interfere with downstream events associated with accessory cell function.
- Wille, John J.,Kydonieus, Agis F.,Murphy, George F.
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- Electronic spectroscopy and photoisomerization of trans-Urocanic acid in a supersonic jet
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trans-Urocanic acid (trans-UA), a component of the epidermal layer of skin, exhibits wavelength-dependent photochemistry. The quantum efficiency of isomerization to cis-UA is greatest when the molecule is excited on the long wavelength tail of its absorption profile in solution (300-320 nm). However, exciting the molecule where it absorbs UV light most efficiently (260-285 nm) causes almost no isomerization. We have used fluorescence excitation and dispersed emission methods in a supersonic jet to investigate the electronic states involved in this complex and interesting photochemistry. Three distinct regions are present in the excitation spectrum. Region I, which is below the isomerization barrier, contains sharp, well-resolved peaks that upon excitation emit from the S1 state of trans-UA. Region II exhibits peaks that increase in broadness and decrease in intensity with increasing excitation energy. Upon excitation these peaks produce dual emission from the S1 states of both trans- and cis-UA. The trans to cis isomerization barrier is estimated to be 1400 cm-1. Region III exhibits excitation to the S2 electronic state and has a broad structure that spans 3000 cm-1 and occurs 4000 cm-1 above S1. S2 excitation results in essentially no trans to cis isomerization.
- Ryan,Levy
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- Concerning the photodiastereomerization and protic equilibria of urocanic acid and its complex with human serum albumin
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Photodiastereomerization of urocanic acid and its human serum albumin complex (its binding constant was estimated to amount 4.1·10 -4dm3·mol-1) was investigated. It was found that although the photodiastereomerization rates were similar, the photoequilibrium positions differed significantly ((E):(Z) = 33:77 for free urocanic acid, and 50:50 for the complex). This is thought to be due to a different stabilization of the corresponding orthogonal excited states. The thermal barrier of diastereomerization was estimated to amount to more than 250 kJ·mol-1 making it a very unlikely process under physiological and photodiastereomerization conditions. The various prototropic species of the two diastereomers at various pH values were analyzed by means of a mathematical model and from these results a novel photoinduced pH-jump methodology allowing for fast, persistent, diffusion controlled, and bidirectional jumps is proposed. Springer-Verlag 2004.
- Schwarzinger, Bettina,Falk, Heinz
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- The effect of molecular environment on the photoisomerization of urocanic acid
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Urocanic acid, imidazole propenoic acid, is a metabolic product of histidine, which accumulates in skin and is excreted in sweat. It absorbs UV radiation at wavelengths shorter than 340 nm, and its principal photochemical reaction is a trans-cis isomerization about the propenyl double bond. This isomerization to the biologically active cis isomer is implicated in the photoinduced suppression of the immune system of skin. The kinetics of the trans → cis photoisomerization of urocanic acid has been determined in a number of solvents, spanning a range of polarities. The initial rates of isomerization and the photostationary trans-cis compositions, in all solvents except water, correlate linearly with solvent polarity. This indicates that the isomerization proceeds through a polar intermediate that is stabilized by coulombic interactions with the molecular environment.
- Wallis, Richard A.,Smith, Gerald J.,Dunford, Cara L.
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- A Nitrogen-15 Nuclear Magnetic Resonance Study of the Acid-Base and Tautomeric Equilibria of 4-Substituted Imidazoles and Its Relevance to the Catalytic Mechanism of α-Lytic Protease
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The pH dependence of the 15NMR shifts of histamine, imidazole-4-propionic acid, imidazole-4-acetic acid, trans- and cis-urocanic acid, and endo-cis-3-(4-imidazoyl)bicyclohept-5-ene-2-carboxylic acid has been determined at the natural-abundance level of 15N.The chemical-shift changes permit calculation of pKa values for the acidic species present as well as reasonably accurate positions of the N1(H)N3(H) tautomeric equilibria for those species having unprotonated imidazole rings.The 15N shifts of cis-urocanic acid and endo-cis-3-(4-imidazoyl)bicyclohept-5-ene-2-carboxylic acid demonstrate that carboxylate-N3(H) hydrogen-bonding interactions can cause the N3(H) tautomers to be substantially more stable than the N1(H) tautomers.The unusual positions of these tautomeric equilibria are quite similar to that found for the histidine of the catalytic triad of α-lytic protease.
- Roberts, John D.,Yu, Chun,Flanagan, Cynthia,Birdseye, Theresa R.
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- Formation of singlet oxygen by urocanic acid by UVA irradiation and some consequences thereof.
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Singlet oxygen-initiated decomposition of urocanic acid (UCA) (3-(1H-imidazol-4(5)-yl)-2-propenoic acid) was used to successfully confirm the report that UCA generates singlet oxygen when irradiated with ultraviolet A light (UVA). The UCA-generated singlet oxygen converts UCA to one or more products that then catalyze the further destruction of the UCA with UVA light by singlet oxygen formation. Some nicking of the phiX-174 supercoiled plasmid DNA was observed when UCA was irradiated with UVA to complete destruction of the starting material, and the product mixture was then mixed with the plasmid in the dark. More extensive nicking was seen when the photoproduct mixture and the plasmid were irradiated with UVA light. An "aged" (4 days) solution of UCA photoproduct no longer caused nicking in the dark but retained the capability to nick the plasmid when irradiated. There is evidence for the presence of hydroperoxides in the UCA photolysis product mixture, and the quenching studies with 2-propanol indicate that free radicals are involved in the plasmid-nicking photochemistry. Singlet oxygen does not appear to play a role in the nicking of the plasmid.
- Menon, Elton L,Morrison, Harry
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- Diffusion of E and Z urocanic amphiphiles through skin and their insertion in a membrane model
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The incorporation of synthetic urocanic amphiphiles into a membrane model is described. A monomolecular film of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol was formed at the air-water interface and used as a model. In parallel, diffusion of these derivatives through the skin was studied using rat skin on flow-through diffusion cells. The flux and the cumulative amount were determined. Although the structure and the composition of the DPPC/cholesterol monolayer differed greatly from multilayers of epidermal lipids, the results obtained in the incorporation and diffusion studies were similar. The structure of the urocanic amphiphiles was very close, but the membranes led to the following flux or insertion classification: Ester E > Ester Z ? Amide E. From the results obtained and for simplicity, the technique of Langmuir monolayers seems to be highly suited to the primary screening of amphiphilic compounds. Copyright
- Sirieix-Plenet,Ader,Miquel,Mavon,Lauth-de Viguerie
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- A stereospecific route to (Z)-Urocanic acids
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(Z)-Urocanic acid and its derivatives can be made stereo-specifically by ring-opening of pyrrolo[l,2-c]imidazol-5-ones in aqueous tetrahydrofuran.
- Despinoy, Xavier L. M.,McNab, Hamish,Tyas, Richard G.
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p. 1676 - 1678
(2008/12/22)
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- THE USE OF UROCANIC ACID BEING ABLE TO ACIDIFY THE CELL CYTOPLASM AND FOR PREVENTING OR HALTING CELLULAR PROLIFERATION IN A PERSON
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This invention relates to the use of urocanic acid or another pharmaceutically acceptable agent being able to acidify the cell cytoplasm, for the manufacture of a pharmaceutical composition useful for causing inhibition or halting of transformed or non-transformed cell proliferation in a person or an animal, wherein an effective amount of said agent is administered in an essentially non-dissociated form to the person or animal. This invention also concerns the use of said agent as an enhancer for other therapeutically active agents. The invention also concerns a pharmaceutical composition.
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(2008/06/13)
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- PHARMACEUTICAL AND COSMETIC COMPOSITIONS COMPRISING UROCANIC ACID DERIVATIVES AS RADICAL SCAVENGERS OR ANTIOXIDANTS
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Upon exposure to UVB, the epidermal component trans-urocanic acid is not only photoisomerized into cis-urocanic acid, but will also, at least in part, be photooxidized into urocanic acid oxidation products. We hypothesized that urocanic acid oxidation products can mimic UV-induced systemic immunosuppression comparable to the suppressive properties already established for cis-urocanic acid. A crude mixture of urocanic acid oxidation products showed a significant suppression of the sensitization phase of the systemic contact hypersensitivity response to picryl chloride. Three of the urocanic acid oxidation products were selected for this study: imidazole-4-carboxylic acid, imidazole-4-carboxaldehyde and imidazole-4-acetic acid. Effects on the sensitization-, elicitation- and post-elicitation phase of contact hypersensitivity to picryl chloride in BALB/c mice were studied and compared to the effects of cis-urocanic acid. Imidazole-4-carboxaldehyde was equally effective at suppressing the sensitization phase as cis-urocanic acid. The triplet combination of the imidazoles showed more pronounced suppression than that induced by cis-urocanic acid. The most effective compounds for the suppression of the elicitation phase appeared to be imidazole-4-acetic acid and cis-urocanic acid. Significant suppression of the post-elicitation phase was only obtained with the triplet combination of imidazole-4-carboxaldehyde, imidazole-4-carboxylic acid and imidazole-4-acetic acid, which combination appeared to be effective at all three tested phases, Because these three urocanic acid oxidation products are present in UVB-exposed human stratum corneum, these compounds may play a role in UVB-induced immunosuppression.
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(2008/06/13)
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- Reactive Oxygen Species Formation by UV-A Irradiation of Urocanic Acid and the Role of Trace Metals in This Chemistry
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We have extended our study of the decomposition of urocanic acid (UCA) with ultraviolet A radiation (UV-A) by the self-sensitized generation of singlet oxygen (see Photochem. Photobiol. 75, 565 [2002]). The chemistry has been found to be partially dependent on the presence of trace metal, most likely iron. Rigorous removal of metal impurities from the reaction mixture, using Chelex, retarded (but did not eliminate) the UV-A-initiated UCA degradation. The addition of small amounts of ferric chloride to the Chelex-treated solutions restored reactivity. Chelex treatment had a modest effect on the previously reported ability of UCA photoproducts to photonick supercoiled plasmid DNA. Also, photoinactivation of Sindbis virus on irradiation with the UCA photoproducts is now reported. Inactivation of the virus by a photoproduct mixture derived from a UCA solution that had been pretreated with Chelex was less rapid and gave better behaved time-course plots than was observed for photoproducts from non-Chelex treated solutions. These results are particularly noteworthy in light of the ubiquitous presence of both UCA and iron in the skin.
- Menon, Elton L.,Perera, Rushika,Kuhn, Richard J.,Morrison, Harry
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p. 567 - 575
(2007/10/03)
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