Benzophenone Moiety Research Articles

Photoaffinity labeling of rat liver glutathione S-transferase, 4-4, by glutathionyl S-[4-(succinimidyl)-benzophenone

Glutathionyl S-[4-(succinimidyl)benzophenone] (GS-Succ-BP), an analogue of the product of glutathione and xenobiotic substrate, was synthesized and shown to act as a photoaffinity label of rat liver glutathione S-transferase, 4-4. A time-dependent photoinactivation occurs upon irradiation at long wavelength UV light of the complex of enzyme and GS-Succ-BP. The rate of inactivation exhibits nonlinear dependence on [GS-Succ-BP], characterized by an apparent KI of 115 microM and kmax of 0.469 min-1. Effective protection against photoinactivation by 150 microM GS-Succ-BP is provided by dinitrophenol, nitrobenzene, ethacrynic acid, and S-hexylglutathione, analogues of xenobiotic substrates and product. These results suggest that GS-Succ-BP reacts with the enzyme within the active site, probably in the xenobiotic substrate-binding site. Upon complete inactivation, reagent incorporation of about 1 mol/mol of enzyme dimer is measured by radioactivity and MALDI-TOF mass spectrometry. Isolation of modified peptides followed by gas-phase sequencing and mass spectrometry indicates that Met-112 is the only reaction target of GS-Succ-BP. Although only one subunit of the enzyme dimer is modified, catalytic activity of both subunits is lost. Molecular modeling suggests that the benzophenone moiety of the compound binds in the cleft between the two enzyme subunits and modification of Met-112 on one subunit excludes reaction of the corresponding methionine on the other subunit. It is proposed that the new compound, glutathionyl S-[4-(succinimidyl)benzophenone], may have general applicability as a photoaffinity label of other enzymes with glutathione binding sites.

Alignment of a nematic liquid crystal induced by anisotropic photo-oxidation of photosensitive polyimide films

The alignment of a nematic liquid crystal (LC) could be induced by three polyimide (PI) films exposed to linearly polarized ultraviolet (UV) light of long wavelength (366 nm). The alignment could also be modified by changing the direction of polarization of the linearly polarized light (LPL). Infrared (IR) and UV-visible spectroscopy indicated that among the three PI films the PI with a benzophenone moiety and the PI with a diphenyl methane moiety were sensitive to UV radiation and susceptible to remarkable ablation after irradiation with LPL in air. Polarized UV-visible spectroscopy indicated that dichroism of the PI films was caused by LPL and altered by changing the polarization of the LPL. Furthermore, the PI films irradiated under vacuum showed little reduction in intensity of IR bands, which is in sharp contrast to the marked decreases in samples irradiated in atmospheres containing oxygen. This proves that oxygen is necessary to the ablative process of the PI films. Our results indicate that the mechanism of LC alignment on the photosensitive PI films is photoinduced anisotropic oxidative ablation of the PI films. In contrast, the PI film with a diphenyl ether moiety was quite stable under similar irradiation conditions even though the irradiated PI film could also induce alignment of the LC molecules.

Photocontact dermatitis from ketoprofen and tiaprofenic acid: cross-reactivity study in 12 consecutive patients.

The arylpropionic acid derivatives (APADs) ketoprofen and tiaprofenic acid can provoke photoallergic dermatitis. Possible cross-reactivity between APADs is of importance in patients using nonsteroidal anti-inflammatory drugs. Because of the similarities in chemical structures, we investigated patients with photoallergy to ketoprofen or tiaprofenic acid, in order to study cross-reactivity between APADs and a possible pattern of cross-reactivity between benzophenone-containing molecules, so as to determine the molecular basis of photoallergy to ketoprofen or tiaprofenic acid. 10 patients with photoallergy to topical ketoprofen, 2 with photoallergy to oral tiaprofenic acid, and 15 control subjects with no history of contact dermatitis from APADs, nor from benzophenone-containing molecules, were photopatch tested in triplicate with ketoprofen, tiaprofenic acid, other APADs (alminoprofen, fenoprofen, flurbiprofen, ibuprofen and naproxen), benzophenone-containing molecules (fenofibrate, oxybenzone, sulisobenzone), and unsubstituted benzophenone. 1 set was irradiated with UVA light, 1 with solar-simulated irradiation and 1 dark control. Tests were read at 2, 3 and 4 days. Patients reacted to both ketoprofen and tiaprofenic acid (12/12), fenofibrate (8/12), oxybenzone (3/12) and unsubstituted benzophenone (11/12), but not to other APADs, nor to sulisobenzone. Tests remained negative in control patients. Photoallergy is due to the benzophenone moiety of ketoprofen, or to the very similar thiophene-phenylketone of tiaprofenic acid, but not to their arylpropionic function. This induces cross-reactivity to fenofibrate and oxybenzone but not to APADs without a benzophenone moiety, which may therefore probably be used in such patients. Unsubstituted benzophenone should be added to standard phototesting series.

A Scalable Synthesis of the Thromboxane Receptor Antagonist 3-{3-[2-(4-Chlorobenzenesulfonamido)ethyl]-5-(4-fluorobenzyl)phenyl}propionic Acid via a Regioselective Heck Cross-Coupling Strategy

A regioselective Heck cross-coupling strategy is presented for the large-scale preparation of the thromboxane receptor antagonist 3-{3-[2-(4-chlorobenzenesulfonamido)ethyl]-5-(4-fluorobenzyl)phenyl}propionic acid (1). Commercially available 3-bromo-5-iodobenzoic acid was first converted to the corresponding acid chloride, and this was then condensed with 4-fluorobenzene via a Friedel−Crafts acylation reaction to give 3-bromo-5-iodophenyl 4-fluorophenyl ketone. Regioselective cross-coupling with ethyl acrylate and then N-vinylphthalimide, each under phosphine-free Heck conditions, led to formation of ethyl 3-[3-(4-fluorobenzoyl)-5-(2-phthalimidovinyl)phenyl]propenoate. Reduction of the benzophenone moiety and saturation of the olefin double bonds, followed by phthalimide ring cleavage, then gave ethyl 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propionate monocitrate salt. This was converted to the sulfonamido-substituted arylpropionic acid 1 via a two-step one-pot procedure in which sulfonamide formation...

Magnetic and electrochemical investigations on anions derived from oligoketones containing fluorenone and benzophenone units. An approach to the design of stable multiradical organic materials

The mono- and poly-anions of some mono-, di- and tetra-ketones containing fluorenone and benzophenone moieties have been studied by NMR and cyclic voltammetry. Alkali metal anion radicals of fluorenone, generated by electron transfer from an alkali metal naphthalene radical anion exhibit markedly lower molar paramagnetic solvent shifts than those generated by direct reduction with an alkali metal. Evidence is provided for the involvement of hyperfine interactions between the naphthalene and the paramagnetic solute. The dianion of the diketone 9 is paramagnetic as are the dianions of the tetraketones 6 and 7. The NMR data, combined with those obtained by cyclic voltammetry, indicate that polyketones possessing fluorenone moieties connected through isophthaloyl ‘spacers’ are promising systems for the preparation of high-spin organics and electrophores.

Photochemical Behavior of Poly(Organophosphazenes). 15. Light-Induced Cross-Linking of [(4-Benzoylphenoxy)x(Methoxyethoxyethoxy)2 − x] Phosphazene Copolymers

The synthesis of a new, highly photosensitive, phosphazene copolymer containing an almost-equimolecular quantity of benzophenone and methoxyethoxyethoxy substituents is reported in this paper, together with the photochemical behavior of this material when irradiated in film both in oxygen and in an argon atmosphere. It has been detected that the photoreactivity of the phosphazene material strongly depends on the light absorption process by the benzophenone moieties, whose selective excitation predominantly brings about an intramolecular hydrogen abstraction reaction from the ethylene oxide units, thus producing highly reactive phosphazene macroradicals. The coupling reactions of these species results in the complete cross-linking of the polyphosphazene substrate and in its total insolubilization. Moreover, the influence of molecular oxygen on the overall photochemical process of the benzophenone/ethyleneoxide-substituted phosphazene copolymer is investigated. The implications of the light-induced reticulation process in the controlled insolubilization of poly[ bis (methoxyethoxyethoxy)phosphazene] are also discussed.

Direct mapping of an agonist-binding domain within the parathyroid hormone/parathyroid hormone-related protein receptor by photoaffinity crosslinking

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are calciotropic hormones interacting with a shared seven-transmembrane domain G protein-coupled receptor, which is located predominantly in bone and kidney. To map the interface of the bimolecular interaction between hormone and receptor, we designed and radioiodinated a bioactive, photoreactive PTH agonist, (125)I-[Nle(8,18),Lys13(epsilon-p-(3-I-Bz)Bz),L-2-Nal(23),Arg(26,2 7),Tyr34] bPTH-(1-34)NH2 ((125)I-all-R-K13). This ligand contains a photoreactive benzophenone moiety attached to the side chain of Lys13. All other lysyl residues are substituted by argynyls. The analog photocrosslinks specifically to the recombinant hPTH/PTHrP receptor stably transfected into human embryonic kidney cells (HEK-293/C-21 cells, approximately 400,000 receptors per cell), generating a diffuse approximately 87-kDa band on SDS/PAGE autoradiography. To identify the "contact domain" within the hPTH/PTHrP receptor involved in binding of (125)I-all-R-K13, the radiolabeled band containing the ligand-receptor conjugate was subjected to chemical and enzymatic cleavage. Two independent pathways of sequential digestion were used: Route A, lysyl endopeptidase C, then endo-N-glycosidase F, followed by cyanogen bromide; Route B, cyanogen bromide followed by endo-N-glycosydase F. The identified domain is in contact with position 13 in (125)I-all-R-K13 and corresponds to amino acids 173-189 of the hPTH/PTHrP receptor, located at the C-terminal region of the N-terminal extracellular domain.

Magnetic Field and Isotope Effects on Photochemistry of Chain-Linked Compounds Containing Benzophenone and Hydrogen-Donor Moieties

The magnetic field effects on the decay kinetics for chain-linked triplet biradicals have been observed by the use of a laser photolysis apparatus with a conventional electromagnet and a pulsed magnet. Biradical lifetimes increase steeply to their maxima from the zero field to ca. 2 T. The biradical decay times tend to decrease gradually with further increase of the magnetic field intensity to 14 T. The decreased lifetimes for triplet biradicals can be explained in terms of spin−lattice relaxation due to hyperfine anisotropy and to g tensor anisotropy.

Thermotropic polyamides containing the benzophenone unit

AbstractThe synthesis and structure‐property relationship of fully aromatic homo‐ and copolyamides are described. They all contain the 3,4′‐substituted benzophenone and diphenyl ether moiety in the main chain. The synthesis of the polyamides was performed at low temperatures with silylated aromatic diamines and aromatic acid chlorides. The polymers possess good solubility in dipolar aprotic solvents. They display thermotropic liquid crystalline properties. Based on results obtained by means of polarization microscopy, X‐ray scattering, and molecular dynamics simulation a rather unusual structure is proposed. It consists of a superlattice composed alternatingly of smectic B layers and amorphous layers. The formation of smectic B layers is untypical for main‐chain LC polymers without aliphatic spacers.

Preparation and Physical Properties of Polyurethane Elastomers Containing Mesogenic Moieties*

The mesogenic diols containing azobenzene, benzophenone and biphenyl moieties with an alkoxy flexible spacer were synthesized, and the linear polyurethanes were prepared by the polyaddition of these diols with diisocyanates such as 2,4-toluene diisocyanate and 4,4'-diphenylmethane diisocyanate. From the measurement of DSC and polarizing optical microscopy with the hot stage, it was found that most resulting polyurethanes revealed a thermotropic liquid crystalline behaviour and the temperature of mesomorphic phase was effected significantly by the molecular structure of diisocyanates and the chain length of flexible spacers. On the other hand, the segmented polyurethanes were prepared by the chain extension of isocyanate-terminated prepolymers with these mesogenic diols. As the results, it was found that the incorporation of mesogenic moieties to the hard segment of the polyurethanes contributed to the enhancement of thermal stability and mechanical properties.

Photoactive Analogs of Farnesyl Pyrophosphate Containing Benzoylbenzoate Esters: Synthesis and Application to Photoaffinity Labeling of Yeast Protein Farnesyltransferase.

Farnesyl pyrophosphate (FPP) is involved in a large number of cellular processes including the prenylation of transforming mutants of Ras proteins implicated in cancer. Photoactive analogs could provide useful information about enzyme active sites that bind farnesyl pyrophosphate; however, the availability of such compounds is extremely limited. Molecules that incorporate benzophenone moieties are attractive photoaffinity labeling reagents because of their useful photochemical properties. Here, the syntheses of two compounds, 3a and 3b, containing para- and meta-substituted benzoylbenzoates are described. Compounds 3a and 3b are competitive inhibitors (with respect to FPP) of yeast protein farnesyltransferase (PFTase) with K(i) values of 910 and 380 nM, respectively. Both compounds inactivate PFTase upon photolysis, resulting in as much as 44% inactivation of enzyme activity. Photolysis of PFTase in the presence of [(32)P]3a or of [(32)P]3b results in preferential labeling of the beta subunit, suggesting that this subunit is involved in prenyl group recognition. These compounds should be valuable tools for studying enzymes that utilize FPP as a substrate.

Photoinduced Inter- and Intra-Ion-Pair Electron Transfer Reactions in N-(p-Benzoylbenzyl)-N,N,N-tri-n-butylammonium Triphenyl-n-butylborate and -Gallate Salts

The photoreduction of N-(p-benzoylbenzyl)-N,N,N-tri-n-butylammonium triphenyl-n-butylborate (1) and gallate (2) was studied using nano- and picosecond laser flash photolysis. An electron transfer reaction from the borate or the gallate counteranion to the excited triplet state of the benzophenone moiety (BP*3) was demonstrated. This reaction leads to the formation of benzophenone radical anion (6) and the boranyl radical, the latter of which dissociates rapidly to form butyl radical. The electron transfer rate was found to depend on the polarity of the solvent. In neat benzene, the short lifetime of the triplet obtained (300 ± 150 ps) indicates an intramolecular process and that the compounds exist as tight ion pairs. The addition of 1% MeCN increases the triplet lifetime up to 1.2 ns. The formation of a solvent-separated ion pair was suggested in this solvent mixture. However, in the polar solvent MeCN, 1 and 2 exist partially as free ions as determined by their dissociation constants. A diffusion-contro...

Synthesis and Characterization of a Novel Polymeric System Bearing a Benzophenone Borate Salt as a New Photoinitiator for UV Curing

Polymeric photoinitiators bearing benzophenone triphenylbutyl borate salt as the side chain have been synthesized and characterized and their activity measured in the photoinitiated polymerization of a bifunctional monomer, diethylene glycol diacrylate. The results were compared with a low-molecular weight model compound. At lower concentrations of the requisite benzophenone moiety, the highest activity was observed for the model compound, while at higher concentrations the homopolymer was superior. For both cases, the lowest photoinitiation activity was observed with significant induction period for copolymers with methyl methacrylate when compared to the homopolymer. The results are discussed in light of the microenvironment of the initiator fragments in the polymeric systems.

A novel synthesis and characterization of phenylacetylene end‐capped poly(aryl ether sulfone) and poly(aryl ether ketone) oligomers

AbstractA series of controlled molecular weight poly(aryl ether sulfone) oligomers with benzophenone moieties at the chain termini were prepared. The two carbonyl groups at the chain ends were converted to ethynyl groups by using trimethylsilyldiazomethane/BuLi in tetrahydrofuran. Reactions of 4,4′‐isopropylidenediphenol with 4,4′‐difluorobenzophenone and 4‐fluorophenylphenylacetylene as the end‐capping reagent in N,N‐dimelthylacetamide afforded the desired poly(aryl ether ketone) oligomers Both sulfone and ketone containing oligomeric polyethers undergo crosslinking reactions at elevated temperatures.

Picosecond Laser Photolysis Studies on Chain-Length, Solvent and Temperature Dependences of the Intramolecular Photoreduction Process of Benzophenone by Diphenylamine

Abstract Photoinduced hydrogen abstraction (HA) processes of 1-(4-anilinophenyl)-2-(4-benzophenoxy)ethane, 1-(4-anilinophenyl)-3-4-benzophenoxy)propane, and 1-(4-anilinophenyl)-8-(4-benzophenoxy)octane (BP–O–(CH2)n–O–DPA: n = 2, 3, and 8) in benzene, acetonitrile, and N,N-dimethylformamide solutions were investigated by means of picosecond transient absorption spectroscopy. In benzene solution, apparent mechanism of the hydrogen abstraction reaction was “direct” process and no absorption spectrum of the charge separated state was observed. The decay of triplet benzophenone moiety (3BP*) was regulated by the dynamic rearrangement process of the mutual geometry between 3BP* and DPA to a more compact one. In polar solutions, the electron transfer (ET) from DPA to 3BP* moiety took place in addition to the direct HA from DPA by 3BP*. The rate of the ET reaction was regulated mainly by the distance between the reactant moieties. Moreover, the intra-ion pair (IP) proton transfer (PT) resulting in the HA product formation was observed, although such PT process in the IP state between the unlinked 3BP* and the secondary amine was not observed. By integrating the present results on the linked systems with those of the unlinked systems, the role of the ET or CT interaction in the HA process of 3BP* from the secondary amine was discussed.

Circular dichroism of ketoprofen complexed to serum albumins: Conformational selection by the protein: A novel optical purity determination technique

Complexation of 2-(3'-benzoylphenyl)propionic acid (ketoprofen), 1, to bovine serum albumin (BSA) results in an intense negative circular dichroism in the ketonic n-->pi* band of the benzoylphenyl moiety. This high CD contrasts with the weak CD of 1-enantiomers dissolved in common solvents. Furthermore, a number of chiral and achiral molecules containing the benzophenone moiety are easily complexed to BSA: all these complexes show an intense CD at the same transition. To account for the observed CD intensities of the above molecules, it appears that BSA complexation markedly shifts the equilibrium between strongly asymmetric, antipodic conformers. Dissymmetry of these conformers is connected to the instability of a structure with phenyl rings coplanar to the carbonyl chromophore, as also indicated by molecular mechanics calculations. The magnification of the Cotton effects of the 1-antipodes, due to the protein, can be used to measure the optical purity of 1-samples with excellent precision. In contrast with BSA, human SA is unable to recognize the chirality of 1-antipodes; oleic acid cocomplexation modifies this fact as well as other features of the binding.

PHOTOCHEMICAL AND PHOTOBIOLOGICAL PROPERTIES OF KETOPROFEN ASSOCIATED WITH THE BENZOPHENONE CHROMOPHORE

Irradiation of ketoprofen in neutral aqueous medium gave rise to 3-ethylbenzophenone as the major photoproduct. Its formation is justified via protonation of a benzylic carbanion or hydrogen abstraction by a benzylic radical. Minor amounts of eight additional compounds were isolated. Four of them are derived from the benzylic radical: 3-(1-hydroperoxyethyl)benzophenone, 3-(1-hydroxyethyl)benzophenone, 3-acetylbenzophenone and 2,3-bis-(3-benzoylphenyl)butane. The other four products involve initial hydrogen abstraction by the excited benzophenone chromophore of ketoprofen: 1,2-bis-(3-ethylphenyl)-1,2-diphenyl-1,2-ethanediol, 2-(3-benzoylphenyl)-1-(3-ethylphenyl)-1-phenylpropan-1-ol, alpha-(3-ethylphenyl)phenylmethanol, 1,2-bis-[3-(2-hydroxycarbonylethyl) phenyl]-1,2-diphenyl-1,2-ethanediol. The latter process was found to mediate the photoperoxidation of linoleic acid through a type I mechanism, as evidenced by the inhibition produced by the radical scavengers butylated hydroxyanisole and reduced glutathione. The major photoproduct, which contains the benzophenone moiety but lacks the propionic acid side chain, also photosensitized linoleic acid peroxidation. Because lipid peroxidation is indicative of cell membrane lysis, the above findings are highly relevant to explain the photobiological properties of ketoprofen.

Ionic chiral handle-induced asymmetric synthesis in a solid state Norrish type II photoreaction

Irradiation of crystals of salts formed between 4-(2,4,6-triisopropylbenzoyl)benzoic acid ( 1a) and various optically active amines is shown to lead to optically active Norrish type II photoproducts in low to moderate enantiomeric excesses, a process in which the ammonium ion has acted as an “ionic chiral handle.” X-ray crystallography reveals that the salts crystallize with two independent, mirror image-related molecules of the benzophenone moiety in the asymmetric unit, and this is suggested to be the source of the low ees observed.

A new photoaffinity analog of cGMP: potent inhibitor of cyclic nucleotide phosphodiesterase.

A purine nucleotide analog, 2'-O-(4-benzoylbenzoyl)guanosine cyclic 3',5'-monophosphate (BBcGMP), was synthesized from 4-benzoylbenzoic acid and cGMP. BBcGMP was found to inhibit several types of cyclic nucleotide phosphodiesterases (PDEs) at low concentrations. Besides its activity as a PDE inhibitor, the benzophenone moiety of BBcGMP provides it with UV light-induced photoreactivity toward organic compounds. This photoreactivity of BBcGMP was exploited to radiolabel specifically the light-stimulated cGMP PDE of the rod outer segment with [alpha-32P]BBcGMP. These results suggest that benzoylbenzoic derivatives of cyclic nucleotides can be of general use in the inhibition of cyclic nucleotide PDEs. The results further suggest that radiolabeled cyclic nucleotide derivatives may be useful in the identification and active site determination of cyclic nucleotide-binding proteins and enzymes.

Polyimides with alicyclic diamines. II. Hydrogen abstraction and photocrosslinking reactions of benzophenone‐type polyimides

AbstractPhotosensitive polyimides with alicyclic diamines and benzophenone moiety were prepared by reactions of 3,3′,4,4′‐benzophenonetetracarboxylic dianhydride (BTDA) with diamines in aprotic solvents, followed by thermal or chemical imidizations. Among them the polyimide from BTDA and bis(4‐amino‐3‐methylcyclohexyl) methane (DMDHM) can be dissolved in several organic solvents such as dichloromethane, tetrachloroethane, and N‐methyl‐2‐pyrrolidone (NMP). In order to compare properties of the polyimides with alicyclic diamines with those of corresponding aromatic polyimides, the UV absorption spectra and fluorescence spectra of these polyimides and their model compounds were investigated. No occurrence of charge transfer at photoexcited states was ascertained for the polyimides with alicyclic diamines. The hydrogen abstraction and crosslinking during photoirradiation have been studied to learn the influence of the elimination of charge transfer process in these photosensitive polyimides. The quantum yield of hydrogen abstraction for the model compound of alicyclic polyimides is 0.56 in THF measured with HPLC. The quantum yield for the photocrosslinking reaction of the solvent‐soluble polyimide with alicyclic diamine, PI(BTDA/DMDHM), was determined to be 0.004 in air from gel permeation chromatography (GPC) measurement, which is four times higher than that for photosensitive polyimides with aromatic diamines. © 1994 John Wiley & Sons, Inc.