Ocular Pharmacokinetic Study of l-Carnosine and N-Acetyl-l-carnosine in Rabbit by Microdialysis Coupled with UPLC-MS-MS

In order to provide useful information for rational drug design, the ocular pharmacokinetics of l-carnosine (CAR) and its acetylized prodrug N-acetyl-l-carnosine (NAC) were investigated. The in vivo microdialysis sampling coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) was developed for continuously simultaneous monitoring of CAR and NAC in rabbit aqueous humor. The measured in vitro recoveries of the probe were 61.3% for CAR and 65.8% for NAC, while in vivo recoveries decreased to 43.1% for CAR and 43.0% for NAC, respectively. The method was sensitive with LLOQ 20.5 ng mL^?1 for CAR and 20.4 ng mL^?1 for NAC. The initial data indicated that the value of C _max and AUC_(0?C??) of NAC were higher than these of CAR (C _max 2305 vs. 1,802 ng mL^?1), (AUC_(0?C??) 1,337 vs. 1,891 ng h mL^?1), which indicated that the NAC exhibited better ocular bioavailability and duration. The method was rapid, specific and sensitive for continuously monitoring of aqueous humor and it was successfully applied to pharmacokinetic studies of CAR and NAC.     

Purification of adipoyl-7-amino-3-deacetoxycephalosporanic acid from fermentation broth using stepwise elution with a synergistically adsorbed modulator

Multicomponent adsorption data of a fermentation broth containing adipoyl-7-amino-3-deacetoxycephalosporanic acid (adipoyl-7-ADCA), a cephalosporin precursor for 7-ADCA, and two key impurities, alpha-hydroxyadipoyl-7-ADCA and alpha-aminoadipoyl-7-ADCA were obtained from batch equilibrium and frontal chromatography tests. Amberlite XAD-1600 was chosen as the resin. A rate model was applied to simulate the chromatograms. An alkaline buffer, which by itself has no affinity for the resin, was used as the eluent. The widely used reversed-phase modulator model is inaccurate in explaining the stepwise elution data. A new model, the induced competition model, has been developed to account for apparent retention of the buffer in the presence of adsorbed species. Close agreement between the simulations and the data was achieved with the new model.     

Total syntheses of Tardioxopiperazine A, Isoechinulin A, and Variecolorin C

First total syntheses of the isoechinulin-type alkaloids: Tardioxopiperazine A, Isoechinulin A, and Variecolorin C have been achieved from a common key intermediate 5, which was derived from a regiocontrolled Stille cross-coupling reaction of an allylindium reagent.     

Theoretical and experimental studies of the electrochemistry of <Emphasis Type="Italic">p</Emphasis>-aminophenol on a golden electrode

The geometric parameters, vibrational frequencies, and thermochemical values of p-quinonimine (p-AQ) and p-aminophenol (p-AP) were computed ab initio (IIF) and by the density functional theory (DFT) method with the 6-31G(d, p) basis set. Cyclic voltammetry with a golden electrode of p-AP solutions in phosphate buffers at pH 7.30 showed that the standard electrode potential of half reaction for p-QI and p-AP was 0.728 V. The standard electrode potentials of half reactions for p-QI and p-AP were calculated using the free energies and solvation energies of p-QI, p-AP, p-benzoquinone (p-BQ), and hydroquinone (p-HQ). The results showed that the standard electrode potential of half reaction for p-QI and p-AP was 0.743 V at the B3LYP/6-31G(d, p) level and 0.755 V at the HF/6-31G(d, p) level. The standard electrode potentials computed at the B3LYP/6-31G(d, p) and HF/6-31G(d, p) levels were close to their experimental values. The article is published in the original.     

Beyond the metal-metal triple bond in binuclear cyclopentadienylchromium carbonyl chemistry

The cyclopentadienylchromium carbonyls Cp(2)Cr(2)(CO)(n) and Cp*(2)Cr(2)(CO)(n) (Cp = eta(5)-C(5)H(5) and Cp* = eta(5)-Me(5)C(5); n = 3, 2) have been studied by density functional theory using the B3LYP and BP86 functionals. Triplet and singlet structures are found for Cp(2)Cr(2)(CO)(3), with the triplet isomer having an apparent Cr[triple bond, length as m-dash]Cr triple bond (2.295 A by BP86) and predicted to have a lower energy than the singlet isomer having an apparent Cr[quadruple bond, length as m-dash]Cr quadruple bond (2.191 A by BP86). Quintet, septet, and singlet structures, as well as a highly spin contaminated triplet structure, were found for the dicarbonyl Cp(2)Cr(2)(CO)(2). In all of the Cp(2)Cr(2)(CO)(n) (n = 3, 2) structures the carbonyls are asymmetric semi-bridging groups, typically with differences of 0.3-0.5 A between the shortest and longest M-C distances. Very little difference was found between the structures and energetics of the corresponding Cp and Cp* derivatives. These DFT studies suggest that the reported unstable photolytic decarbonylation product of Cp*(2)Cr(2)(CO)(4), characterized only by its infrared nu(CO) frequencies, is the singlet isomer of the tricarbonyl Cp*(2)Cr(2)(CO)(3).     

Supermolecule density functional calculations suggest a key role for solvent in alkaline hydrolysis of p-nitrophenyl phosphate

Supermolecule density functional theory calculations show that solvent is responsible for the concerted transition state in alkaline hydrolysis of p-nitrophenyl phosphate suggested by heavy atom kinetic isotope effects.     

Theoretical study on the isomeric structures and the stability of silylenoid (Tsi)Cl2SiLi (Tsi = C(SiMe3)3)

The structures and isomerization of silylenoid (Tsi)Cl(2)SiLi (Tsi = C(SiMe(3))(3)) were studied by density functional theory (DFT) at the B3LYP/6-31G(d) level. Four equilibrium structures and three isomeric transition states were located. The three-membered ring and p-complex structures, 1 and 2, are the two most stable forms. Two other local minima, the sigma-complex 3 and tetrahedron structure 4, should rearrange to 1 with very low barriers, and then to the most stable isomer 2. To exploit further the stability of silylenoid (Tsi)Cl(2)SiLi, the insertion reactions of 2 and silylene (Tsi)ClSi into the HF molecule have been investigated at the B3LYP/6-31G(d) level, respectively. The results show that the insertion of 2 into HF is very similar to that of (Tsi)ClSi into HF, but the latter is more favorable. To probe the influence of the substituent Tsi on the stability of silylenoid (Tsi)Cl(2)SiLi, the isomers and insertion reaction of silylenoid CH(3)Cl(2)SiLi were investigated in a similar way of those with (Tsi)Cl(2)SiLi. The results indicate that silylenoid containing very bulky group Tsi exhibits unusual stability because of the severe steric hindrance produced by Tsi at the center to which it is attached.     

Experimental and theoretical study of the infrared spectra of BrHI- and BrDI-

Gas phase vibrational spectra of BrHI- and BrDI- have been measured from 6 to 17 microm (590-1666 cm(-1)) using tunable infrared radiation from the free electron laser for infrared experiments in order to characterize the strong hydrogen bond in these species. BrHI-.Ar and BrDI-.Ar complexes were produced and mass selected, and the depletion of their signal due to vibrational predissociation was monitored as a function of photon energy. Additionally, BrHI- and BrDI- were dissociated into HBr (DBr) and I- via resonant infrared multiphoton dissociation. The spectra show numerous transitions, which had not been observed by previous matrix studies. New ab initio calculations of the potential-energy surface and the dipole moment are presented and are used in variational ro-vibrational calculations to assign the spectral features. These calculations highlight the importance of basis set in the simulation of heavy atoms such as iodine. Further, they demonstrate extensive mode mixing between the bend and the H-atom stretch modes in BrHI- and BrDI- due to Fermi resonances. These interactions result in major deviations from simple harmonic estimates of the vibrational energies. As a result of this new analysis, previous matrix-isolation spectra assignments are reevaluated.