Biomedical subjects
Publications and source records attributed to Nicholas J Turro.
The synthesis of diaryloxydiazirines, precursors to diaryloxycarbenes, is described. Thermolyses of the diazirines afford anticipated carbene products, but photolyses afford both carbenes and aryloxy radicals by alpha-scission. UV spectra of the carbenes and radicals are observed. [reaction: see text]
Oxazolidinone-substituted enecarbamates represent a mechanistically rich system for the study of stereoelectronic, steric, and conformational effects on stereoselectivity and mode selectivity in (1)O(2) [2 + 2] and ene reactions. Photooxygenation of these enecarbamates with (1)O(2) leads to diastereomerically pure dioxetanes that decompose to yield an oxazolidinone carbaldehyde and one of the two enantiomers of methyldesoxybenzoin in enantiomeric excess. Stereoselectivity originates at the allylic stereocenter, a result supported by quenching studies, computational analysis, and deuterium solvent isotope effects. [reaction: see text]
Irradiation of biphenyl encapsulated in the cavities of a NaZSM-5 zeolite framework has been reported to result in the formation of an extremely long-lived radical cation. Here, we show that such zeolite encapsulated radical cations can act as irreversible one-electron oxidants for simple alkenes and dienes, in a solid-state analogue to solution-phase cosensitization. Compared to the well-known semiconductor photooxidizers, such as titanium dioxide, the NaZSM-5 zeolite-based solid photooxidants exhibit enhanced selectivity based on oxidation potential, molecular size and shape, and Lewis base character.
[reaction: see text] Reactions in which zeolites are modified with chiral inductors to serve as media for chiral induction are often limited by the propensity of both substrate and inductor to occupy the same supercage. Herein, we report a "ship in bottle" strategy utilizing the thermal decomposition of dioxetanes obtained from oxazolidinone-substituted enecarbamates for the enantioselective generation of methyl desoxybenzoin (MDB). Photoexcitation of the supramolecular geminate molecular pair results in enrichment of the opposite enantiomer of MDB.
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Three single-stranded DNA molecules of different lengths were synthesized and characterized, each containing a fluorescent dye (6-carboxyfluorescein) connected to the 5' end via a photocleavable 2-nitrobenzyl linker and a biotin moiety at the 3' end. UV irradiation (lambda approximately 340 nm) of solutions containing these fluorescent DNA molecules caused the complete cleavage of the nitrobenzyl linker, separating the fluorophore from the DNA. The photocleavage products were characterized by HPLC and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. Our experimental results indicated that the proximity of the chromophore 6-carboxyfluorescein to the 2-nitrobenzyl linker did not hinder the quantitative photocleavage of the linker in the DNA molecules. The biotin moiety allowed immobilization of the fluorescent DNA on streptavidin-coated glass chips. The photocleavage of the immobilized DNA was investigated directly by fluorescence spectroscopy. The results demonstrated that close to 80% of the fluorophore was removed from the immobilized DNA after UV irradiation at 340 nm. These results strongly support the application of the 2-nitrobenzyl moiety as an efficient photocleavable linker, connecting fluorescent probes to DNA molecules for a variety of biological analyses such as DNA sequencing by synthesis.
DNA sequencing by synthesis during a polymerase reaction using laser-induced fluorescence detection is an approach that has a great potential to increase the throughput and data quality of DNA sequencing. We report the design and synthesis of a photocleavable fluorescent nucleoside triphosphate, one of the essential molecules required for the sequencing-by-synthesis approach. We synthesized this nucleoside triphosphate by attaching a fluorophore, 4,4-difluoro-5,7-dimethyl-4-bora-3alpha,4alpha-diaza-s-indacene propionic acid (BODIPY), to the 5 position of 2'-deoxyuridine triphosphate via a photocleavable 2-nitrobenzyl linker. We demonstrate that the nucleotide analogue can be faithfully incorporated by a DNA polymerase Thermo Sequenase into the growing DNA strand in a DNA-sequencing reaction and that its incorporation does not hinder the addition of the subsequent nucleotide. These results indicate that the nucleotide analogue is an excellent substrate for Thermo Sequenase. We also systematically studied the photocleavage of the fluorescent dye from a DNA molecule that contained the nucleotide analogue. UV irradiation at 340 nm of the DNA molecule led to the efficient release of the fluorescent dye, ensuring that a previous fluorescence signal did not leave any residue that could interfere with the detection of the next nucleotide. Thus, our results indicate that it should be feasible to use four different fluorescent dyes with distinct fluorescence emissions as unique tags to label the four nucleotides (A, C, G, and T) through the photocleavable 2-nitrobenzyl linker. These fluorescent tags can be removed easily by photocleavage after the identification of each nucleotide in the DNA sequencing-by-synthesis approach.
A considerably arduous test of a novel class of composite materials consisting of [Ru(bpy)3]2+ and TiO2 codoped zeolites Y is presented here. The [Ru(bpy)3]2+ and TiO2 codoped zeolites Y served as photocatalysts in the oxidation of the model compounds 2,4-dimethylaniline (2,4-xylidine) by H2O2 in an acidic aqueous medium. Zeolite-embedded TiO2 (nano)particles play an important role in the degradation mechanism. The first step in this complex mechanism is the photoelectron transfer from photoexcited [Ru(bpy)3]2+*, located inside the supercage of zeolite Y, to a neighboring TiO2 nanoparticle. During this electron transfer process, electron injection into the conduction band of TiO2 is achieved. The second decisive step is the reaction of this electron with H2O2, which was previously chemisorbed at the surface-region of the TiO2 nanoparticles. In this reaction, a TiO2 bound hydroxyl radical (TiO2-HO.) is created. This highly reactive intermediate initiates then the oxidation of 2,4-xylidine, which enters the zeolites framework in its protonated form (Hxyl+). The formation of 2,4-dimethylphenol as first detectable reaction product indicated that this oxidation proceeds via an electron transfer mechanism. Furthermore, [Ru(bpy)3]3+, which was created in the initiating photoelectron transfer reaction between [Ru(bpy)3]2+* and TiO2, also takes place in the oxidation of Hxyl+. [Ru(bpy)3]2+ is recycled in that reaction, which also belongs to the group of electron transfer reactions. In addition to the primary steps of this particular Advanced Oxidation Process (AOP), the dependence of the efficiency of the 2,4-xylidine degradation as a function of the [Ru(bpy)3]2+ and TiO2 loadings of the zeolite Y framework is also reported here. The quenching of [Ru(bpy)3]2+* by H2O2 as well as the photocatalytic activity of the [Ru(bpy)3]2+ and TiO2 codoped zeolite Y catalysts both follow a distinct percolation behavior in dependence of their TiO2 content.
Contrary to what is known about cis-1,2-diphenylcyclopropane and its derivatives, we find that they have triplet energies of ca. 311 kJ mol(-1), do not undergo intersystem crossing upon direct excitation, undergo the less common adiabatic photoisomerization to the corresponding trans isomers, and show emission from excited 1,3-diradical intermediates.
Photolysis of dibenzyl ketone derivatives adsorbed on ZSM-5 zeolites produces persistent benzyl radicals (initiator radicals), which add to methyl acrylates (monomers) to generate persistent adduct radicals. Both initiator and adduct radicals are readily observable by conventional steady-state EPR spectroscopy at room temperature and are persistent for time periods ranging from seconds to many days. The rate of the formation and the amount of the adduct persistent radical formed depends on the structure of the initiator radical (benzyl radical derivative) and the structure of the monomer (acrylate derivative). The lifetimes of the initiator and adduct radicals depend on the supramolecular structure of the radical@zeolite complex and the diffusion and reaction dynamics of the radicals in the complex. The most intense signal and highest addition rate to methyl acrylate were observed for the smallest initiator radical, the benzyl radical, because of its high mobility and relatively rapid diffusion within the internal zeolite surface. With increasing length of an alkyl chain (methyl, ethyl, and pentyl) on either the initiator (alpha position of the radical) or monomer (alkyl group of acrylate ester), the rate of radical addition to the monomer decreased, a result that is consistent with the decreased mobility and diffusion of the initiator radical or monomer. Deuterium isotope experiments and variation of the methyl acrylate concentration demonstrated that the initial adduct radical from methyl acrylate adds to another methyl acrylate to generate a secondary adduct radical, which, in turn, can continue to propagate to form a polymer that is cross-linked to the zeolite crystals. The results demonstrate that EPR can be a powerful tool for the direct in situ analysis of supramolecular photochemistry involving radicals rendered persistent by supramolecular steric effects. The latter eliminate the need for sophisticated flash photolysis equipment to investigate the structure and dynamics of reactive radicals and require only the use of simpler steady-state lamps.
A series of substituted benzoyl radicals has been generated by laser flash photolysis of alpha-hydroxy ketones, alpha-amino ketones, and acyl and bis(acyl)phosphine oxides, all of which are used commercially as photoinitiators in free radical polymerizations. The benzoyl radicals have been studied by fast time-resolved infrared spectroscopy. The absolute rate constants for their reaction with n-butylacrylate, thiophenol, bromotrichloromethane and oxygen were measured in acetonitrile solution. The rate constants of benzoyl radical addition to n-butylacrylate range from 1.3 x 10(5) to 5.5 x 10(5) M(-1) s(-1) and are about 2 orders of magnitude lower than for the n-butylacrylate addition to the counterradicals that are produced by alpha-cleavage of the investigated ketones. Density functional theoretical calculations have been performed in order to rationalize the observed reactivities of the initiating radicals. Calculations of the phosphorus-centered radicals generated by photolysis of an acyl and bis(acyl)phosphine oxide suggest that P atom Mulliken spin populations are an indicator of the relative reactivities of the phosphorus-centered radicals. The alpha-cleavage of (2,4,6-trimethylbenzoyl)phosphine oxide was studied by picosecond pump-probe and nanosecond step-scan time-resolved infrared spectroscopy. The results support a mechanism in which the alpha-cleavage occurs from the triplet excited state that has a lifetime less than or equal to the singlet excited state.
The geometry of the double bond in oxazolidinone-substituted ene carbamates controls the mode selectivity (ene reaction versus [2+2] cycloaddition) of singlet oxygen through stereoelectronic effects, whereas the chiral auxiliary provides high diastereoselectivity through steric shielding.
The reactions of carbon centered radical pairs often involve diffusion controlled combination and/or disproportionation reactions which are non-selective. A triplet geminate pair of radicals is produced by the photolysis of suitable ketones. The reactions of such geminate pairs can be controlled though the application of supramolecular concepts which emphasize non-covalent interaction to "steer" the geminate pair toward a selected pathway. In addition, "superdupermolecular" concepts, which emphasize the control of radical pair reactions through the orientation of electron spins, can be employed to further control the course of geminate pair reactions. Examples of control of a range of the selectivity of geminate radical combinations, which form strong covalent bonds, through supramolecular and superdupermolecular effects will be presented for the photolysis of ketones adsorbed in the supercages of zeolites.
The rates of phosphorescence decay of 4,7-dimethylindanone (2), 6,9-dimethylbenzosuberone (3), and several related compounds have been analyzed between 4 and 100 K to determine the contributions of intramolecular hydrogen atom tunneling from the o-methyl group to the excited state carbonyl oxygen. Changes in the benzocycloalkanone ring size from five to seven not only affect the geometry at the reaction center, but they also affect the electronic configuration of the triplet excited state in a significant manner. While the triplet state of 5,8-dimethyltetralone (1) in nonpolar glasses can be clearly described as having a predominant n,pi configuration, compounds 2 and 3 have a significantly larger contribution of the less reactive pi,pi state. 4,7-Dimethylindanone (2) is stable under cryogenic conditions and in solution at ambient temperature. In contrast, triplet lifetimes and product analysis indicate that 6,9-dimethylbenzosuberone (3) reacts by quantum mechanical tunneling at temperatures as low as 4 K. A surprisingly small isotope effect k(H)/k(D) approximately 1.1 between 4 and 50 K increases steadily up to k(H)/k(D) approximately 5.1 at 100 K. This unusual observation is interpreted in terms of a vibrationally activated quantum mechanical tunneling process with hydrogen atom transfer at the lowest temperatures being mediated by zero-point-energy reaction-promoting skeletal motions. Results presented here indicate that the combined effects of increasing pi,pi character and unfavorable reaction geometry contribute to the diminished reactivity of o-methyl ketones 2 and 3 as compared to those of tetralone 1.
Photolysis of the supramolecular complexes (dibenzyl ketones@ZSM-5) produced supramolecular complexes of benzyl radicals@ZSM-5, which were directly detected by CW-EPR spectroscopy, and provided information on the dynamics of the radicals. The lifetimes of the radicals increased as the group X attached to the carbon atom at the radical center increases from X = H (t(1/2) ca. 2 min) to X = (CH(2))(4)CH(3) (t(1/2) > 200 min). In addition, line broadening of the EPR signal was observed as the group X increases. Experiments involving cation-exchanged zeolites (MZSM-5; M = Li, Na, K, Rb, Cs) showed a strong dependence of the radical lifetime on the size of the cation (t(1/2) ca. 10 min for Li and t(1/2) > 200 min for Cs). The results are discussed in terms of supramolecular steric effects on the radical-radical reactions in the zeolite supercages.
The photooxygenation of oxazolidinone-substituted enecarbamates leads to diastereomerically pure dioxetanes. The high diastereoselectivity is rationalized in terms of effective pi-facial control achieved by shielding one side of the double bond with the chiral auxiliary. The absolute configuration of the dioxetanes is assigned by derivatization to diols.
Chiral recognition of protein-binding sites by a simple organic molecule with selectivities >100 is reported here. The l-isomer of 4(1-pyrene)-3-butyroyl-phenylalanine amide (Py-L-Phe) binds to BSA with an affinity constant (K(b)) of 3 x 10(7) M(-1), whereas the corresponding D-isomer (Py-D-Phe) binds 100 times weaker. The enantiomers showed contrasting spectral changes when bound to BSA. Whereas hypochromism was observed with the L-isomer, hyperchromism was observed for the D-isomer, and, whereas the fluorescence of the L-isomer was quenched, the fluorescence of the D-isomer was enhanced. The induced CD spectra of the enantiomers bound to BSA bear a near mirror-image relationship. In contrast, the enantiomers show only moderate binding selectivity with lysozyme. The differences in the enantioselectivities with the two proteins indicate that the binding site of 4(1-pyrene)-3-butyroyl-phenylalanine amide (Py-Phe) in BSA is crowded, whereas that of lysozyme is more accommodative of either isomer. The enantioselective binding of Py-Phe isomers is further examined in protein photocleavage studies. Py-D-Phe cleaves BSA and lysozyme at a single site in a manner similar to Py-L-Phe, but the cleavage yields are lower for the d-isomer. Sequencing of the resulting fragments indicated that the photocleavage sites of Py-D-Phe on BSA and lysozyme are identical to those of Py-L-Phe. Flash photolysis studies indicated only minor differences between the two enantiomers. The large binding selectivities, therefore, do not influence cleavage specificity or cleavage site location. The strong role of the single asymmetric center of Py-Phe in recognition and its minor role in photocleavage chemistry are demonstrated.
Photolysis of ketones (1, 1-oMe, 2, 2-oMe, 3, and 4) adsorbed on ZSM-5 zeolites produces persistent carbon-centered radicals that can be readily observed by conventional steady-state EPR spectroscopy. The radicals are persistent for time periods of seconds to many hours depending on the supramolecular structure of the initial radical@zeolite complex and the diffusion and reaction dynamics of radicals produced by photolysis. The structures of the persistent radicals responsible for the observed EPR spectra are determined by a combination of alternate methods of generation of the same radical, by deuterium substitution, and by spectral simulation. A clear requirement for persistence is that the radicals produced by photolysis must either separate and diffuse from the external to the internal surface or be generated within the internal surface and separate and diffuse apart. The persistence of radicals located on the internal surface is the result of inhibition of radical-radical reactions. Radicals that are produced on the external surface and whose molecular structure prevents diffusion into the internal surface are transient because radical-radical reactions occur rapidly on the external surface. The reactions of the persistent radicals with oxygen and nitric oxide were directly studied in situ by EPR analysis. In the case of reaction with oxygen, persistent peroxy radicals are formed in high yield. The addition of nitric oxide scavenges persistent radicals and leads initially to a diamagnetic nitroso compound, which is transformed into a persistent nitroxide radical by further photolysis. The influence of variation of radical structure on transience/persistence is discussed and correlated with supramolecular structure and reactivity of the radicals and their parent ketones.