Efficient synthesis of nucleoside aryloxy phosphoramidate prodrugs utilizing benzyloxycarbonyl protection

An efficient method for the synthesis of nucleoside phosphoramidates prodrugs (6a-f) has been developed that employs a simple protection/deprotection sequence of the nucleoside with benzyloxycarbonyl (Cbz). The coupling reaction of Cbz-protected derivatives (5a-f) with phenyl-(ethoxy-l-alaninyl)-phosphorochloridate (7), followed by Cbz group removal by hydrogenolysis provided the phenyl phosphoramidate ProTides (6a-f) in excellent overall yields.     

Nonribosomal peptide synthesis in animals: the cyclodipeptide synthase of Nematostella

Cyclodipeptide synthases (CDPSs) are small enzymes structurally related to class-I aminoacyl-tRNA synthetases (aaRSs). They divert aminoacylated tRNAs from their canonical role in ribosomal protein synthesis, for cyclodipeptide formation. All the CDPSs experimentally characterized to date are?bacterial. We show here that a predicted CDPS from the sea anemone Nematostella vectensis is an active CDPS catalyzing the formation of various cyclodipeptides, preferentially containing tryptophan. Our findings demonstrate that eukaryotes encode active CDPSs and suggest that all CDPSs have?a similar aminoacyl-tRNA synthetase-like architecture and ping-pong mechanism. They also raise questions about the biological roles of the cyclodipeptides produced in bacteria and eukaryotes.     

Linear and nonlinear optical properties of cationic bipyridyl iridium(III) complexes: tunable and photoswitchable?

A series of cationic Ir(III) substituted bipyridyl ()(N(∧)N (N(∧)N-bpy) complexes incorporating electron-donor and -acceptor substituents, [Ir(C(∧)N-ppy-R')(2)(N(∧)N-bpy-CH═CH-C(6)H(4)-R)][X] (X(-) = PF(6)(-) or C(12)H(25)SO(3)(-)), 2 (a, R = NEt(2) and R' = Me; b, R = O-Oct and R' = Me; c, R = NO(2) and R' = C(6)H(13); C(∧)N-ppy = cyclometalated 2-phenylpyridine, [Ir(C(∧)N-ppy-Me)(2)(N(∧)N-bpy-CH═CH-thienyl-Me)][PF(6)], 2d, and the dithienylethene (DTE)-containing complex 2e have been synthesized and characterized, and their absorption, luminescence, and quadratic nonlinear optical (NLO) properties are reported. Density functional theory (DFT) and time-dependent-DFT (TD-DFT) calculations on the complexes facilitate a detailed assignment of the excited states involved in the absorption and emission processes. All five complexes are luminescent in a rigid glass at 77 K, displaying vibronically structured spectra with long lifetimes (14-90 μs), attributed to triplet states localized on the styryl-appended bipyridines. The second-order NLO properties of 2a-d and related complexes 1a-d with 1,10-phenanthrolines have been investigated by both electric field induced second harmonic generation (EFISH) and harmonic light scattering (HLS) techniques. They are characterized by high negative EFISH μβ values which decrease when the ion pair strength between the cation and the counterion (PF(6)(-), C(12)H(25)SO(3)(-)) increases. The EFISH response is mainly controlled by metal-to-ligand charge-transfer/ligand-to-ligand charge-transfer (MLCT/L'LCT) processes. A combination of HLS and EFISH techniques is used to evaluate both the dipolar and octupolar contributions to the total quadratic hyperpolarizability, demonstrating that the major contribution is controlled by the octupolar part. The incorporation of a photochromic DTE unit into the N(∧)N-bpy ligand (complex 2e) allows the luminescence to be switched ON or OFF. The photocyclisation of the DTE unit can be triggered by using either UV (365 nm) or visible light (430 nm), leading to an efficient quenching of the ligand-based 77 K luminescence, which can be restored upon irradiation of the closed form at 715 nm. In contrast, no significant modification of the EFISH μβ value is observed upon photocyclization, suggesting that the quadratic NLO response is dominated by the MLCT/L'LCT processes, rather than by the intraligand excited states localized on the substituted bipyridine ligand.     

Determination of the enantiomeric excess of α-hydroxy acids

This work describes a convenient and accurate method for optical purity determination of α-hydroxy acids. Their derivatization with commercially available valine methyl ester affords diastereoisomers easily separable by HPLC using achiral C₁₈ columns.     

Size-dependent thermodynamic properties of silver aggregates. Simulation of the photographic development process

Pulse radiolysis and time-resolved optical spectroscopy were used to observe the earliest steps of silver aggregation in the presence of an electron donor whose electrochemical potential is close to those of usual photographic developers. A critical size has to be reached by the silver aggregate before it is thermodynamically able to accept electrons from the donor, then to grow by an autocatalytic process with alternate adsorption of Ag⁺ ions and electron scavenging. From a computer simulation the critical aggregation numbern _c is found to be 4 and hence the electrochemical potential of the critical aggregate is ≈?0.4 V/NHE. The size-dependence of the electrochemical potential in an aqueous solution is discussed and compared with that of the ionization potential in the gas phase. A tentative extrapolation of the present interpretation to the mechanism of the photographic development is proposed.     

Amperometric bienzyme electrode for l-carnitine

An electrochemical sensor with two soluble enzymes allows assay of 0.1–10 mM, l- carnitine with an accuracy of 2%. The assay takes about 2 min. The first enzyme, carnitine dehydrogenase, catalyzes the oxidation of l-carnitine by NAD⁺. The NADH formed is oxidized by hexacyanoferrate(III) in a reaction catalyzed by diaphorase, and the hexacyanoferrate(II) produced is oxidized by electrolysis at 0.3 V. The sensor can be used for several days.     

Atomic XAFS as a tool to probe the electronic properties of supported noble metal nanoclusters

Atomic XAFS is a very attractive technique for probing electronic properties of supported metal nanoclusters. For platinum nanoparticles on different supports, the technique is found to be in good agreement with infrared CO adsorption measurements. The advantages of AXAFS, however, are that no probe molecule is required and that real-time measurements under reaction conditions are possible.