Vertical excitation as a transient phenomenon

For a particular model with two electronic states, each with two vibrations, the dipole correlation function governing electronic absorption is e ^?iωOt cosγt with spectrum ω ₀±γ. The function starts as e ^?iωOt (γ?ω ₀), with Fourier transform peaking around ω ₀ instead of ω ₀±γ, and this is associated with vertical excitation. After a time t～2/γ the spectrum goes over into the normal one. As a generalization, a procedure is outlined for characterizing the state reached first after interaction with light is initiated. Finally it is suggested that one can understand aspects of internal conversion by analogy with the case of vertical excitation.     

Addressing the metabolic activation potential of new leads in drug discovery: a case study using ion trap mass spectrometry and tritium labeling techniques

Metabolic activation of drug candidates to electrophilic reactive metabolites that can covalently modify cellular macromolecules may result in acute and/or idiosyncratic immune system-mediated toxicities in humans. This presents a significant potential liability for the future development of these compounds as safe therapeutic agents. We present here an example of an approach where sites of metabolic activation within a new drug candidate series were rapidly identified using online liquid chromatography/multi-stage mass spectrometry on an ion trap mass spectrometer. This was accomplished by trapping the reactive intermediates formed upon incubation of compounds with rat and human liver microsomes as their corresponding glutathione conjugates and mass spectral characterization of these thiol adducts. Based on the structures of the GSH adducts identified, potential sites and mechanisms of bioactivation within the chemical structure were proposed. These metabolism studies were interfaced with iterative structural modifications of the chemical series in order to block these bioactivation sites within the molecule. This strategy led to a significant reduction in the propensity of the compounds to undergo metabolic activation as evidenced by reductions in the irreversible binding of radioactivity to liver microsomal material upon incubation of tritium-labeled compounds with this in vitro system. With the efficiency and throughput achievable with such an approach, it appears feasible to identify and address the metabolic activation potential of new drug leads during routine metabolite identification studies in an early drug discovery setting.     

Intramolecular Carbenoid Reactions of Pyrrole Derivatives Efficient Syntheses of Pyrrolizinone and Dihydroindolizinone

The copper-catalyzed pyrolysis of 1-diazo-3-(pyrrol-1-yl)-2-propanone (1a) and 1-diazo-4-(pyrrol-1-yl)-2-butanone (1b) in benzene solution gave 1 H-pyrrolizin-2-(3H)-one (4a) and 5,6-dihydroindolizin-7 (8H)-one (4b) , respectively, in quantitative yield. Similar pyrolysis of 1-diazo-4-(3-methylindol-1-yl)-2-butanone (9) was less efficient giving 1-methylbenzo[b]-5,6-dihydroindroindolizin-7 (8H)-one (10) and 4-(3-methylindol-1-yl)-but-l-en-3-one (11) in 7% and 24% yield, respectively.     

Stabilization of platinum(II) hydrides by tri-t-butylarsine; facile syntheses of stable trans-PtH2[As(t-Bu)3]2 and trans-PtHX[As(t-Bu)3]2 complexes

trans-PtH₂[As(t-Bu)₃]₂ was prepared in very good yield by afacile reaction of K₂PtC1₄ with As(t-Bu)₃ in alkaline ethanol. Treatment of trans-PtH₂[As(t-Bu)₃]₂ with CF₃CO₂H or HCI afforded trans-PtH(O₂CCF₃)[As(t-Bu)₃]₂ or trans-PtHCl[As(t-Bu)₃]₂. respectively, in almost quantitative yield.     

Two types of intramolecular addition of an Al-N multiple-bonded monomer LAlNAr' arising from the reaction of LAl with N3Ar' (L = HC[(CMe)(NAr)]2, Ar' = 2,6-Ar2C6H3, Ar = 2,6-iPr2C6H3)

The reaction of beta-diketiminated aluminum(I) monomer LAl with a large bulky azide N3Ar' (L = HC(CMeNAr)2, Ar' = 2,6-Ar2C6H3, Ar = 2,6-iPr2C6H3) in the temperature range from -78 degrees C to room temperature affords two different isomers 2 and 3, which have been characterized by spectroscopic and X-ray structural analyses, as well as elemental analysis. The variable-temperature 1H NMR kinetic studies of this reaction indicate the existence of the monomer LAlNAr' (1) at low temperature and the thermal stability of the compounds increases in the order of 1 < 2 < 3.     

Optimized separation of scopoletin and umbelliferone and cis-trans isomers of ferulic and p-coumaric acids by reverse-phase high-performance liquid chromatography

A systematic optimization strategy for reverse-phase h.p.l.c. is used to produce complete separation of all components of a mixture containing two coumarins, umbelliferone and scopoletin, and the cis-trans isomers of two cinnamic acids, p-coumaric and ferulic. A series of experiments gives retention time data for each of these substances in four citric acid-buffered mobile phases. A mathematical model fitted to this data gives model parameters that provide the basis for a window diagram of relative retentions vs. mobile phase pH. The window diagram gives an estimate of the mobile phase pH required for optimum separation.     

Multisample probe for fast-atom bombardment / mass spectrometry

An inexpensive multisample fast-atom bombardment (FAB) probe assembly was designed for high-throughput analysis of samples on a VG ZAB-SE mass spectrometer. The system consists of a vacuum lock system and a FAB probe whose tip contains five or more sample wells. The probe enters the mass spectrometer source region perpendicular to the secondary ion beam axis, The probe is maintained at high voltage on contact with a spring clip attached to the screen plate of the source block. Sample throughput with the multisample probe is twice that of a coaxial probe, with about twice the sensitivity and no sample cross contamination.     

Triazine chemistry VIII. 2,5-dihydro-5-oxo-1,2,4-triazines

2,5-Dihydro-5-oxo-1,2,4-triazine and some of its alkylated derivatives have been prepared. Nmr spectroscopic analysis has established that the 2,5-dihydro-5-oxo tautomers are preferred over the 4,5-dihydro-5-oxo ones. This preference, and the behavior of 1,2,4-triazines in some other chemical reactions has been interpreted in terms of electron-electron repulsions between the lone pairs of electrons of N₁ and N₂ in this ring system.     

Efficient synthesis of p-bis-(chlorodifluoromethyl)benzene

Selective, high yield partial fluorination of p-bis-(trichloromethyl)benzene to p-bis-(chlorodifluoromethyl)benzene has been accomplished by warming a slurry of the p-bis-(trichloromethyl)benzene in anhydrous HF which also contains a small quantity of inert solvent, such as 1,2-dichloroethane.     

Partition and binding constants in micelles and vesicles from fluorescence quenching data

A method of analysing steady-state fluorescence quenching in compartmentalized systems is proposed which allows the evaluation of partition and binding constants where both association processes occur simultaneosly. The number of binding sites is shown to be dependent on the nature of the quencher.