Substituent effects in the fragmentation reactions of acetanilides and phenyl acetates

The mass spectra of a group of m- and p-substituted acetanilides were measured to determine the effect of the substituents, if any, on the rate of C₂H₂O expulsion (rearrangement) vs. the rate of [CH₃CO]⁺ formation (simple cleavage). Our results agree with observations of others in that substituents which raise the ionization potential of the aromatic ring appear to localize, on the average, less charge density on this locus, and conversely. The atomic composition of the substituent, however, irrespective of its position, seems to determine the relative rates of the competing reaction. Although in several cases Z_m/Z_p values were close to unity, rearrangement of isomeric molecular ions to a common species is shown not to occur.     

J Aggregation of Thiacarbocyanine in Aqueous Gelatin Solutions

The aggregation processes of 3,3′-disulfopropyl-4,4′,5,5′-dibenzo-9-ethylthiacarbocyanine betaine were studied in aqueous gelatin solutions. Gelatin molecules were shown to favor the formation of J aggregates from dye dimers according to the block mechanism. Acidic gelatins much stronger favor J aggregation of the dye than alkaline and, especially, modified gelatins. High contents of microgels and high-molecular-mass fractions in gelatin retard the formation of long-wavelength aggregates.     

Vinylcyclopropanation of norbornadiene,norbornene, and dispiroheptadiene by methyl esters of 1-alkylcyclopropene-3-carboxylic acids

Methyl esters of 1-alkylcyclopropene-3-carboxylic acids (I) in the presence of CuCl·P(OPh)₃ cyclopropanate the intracyclic norbornene double bonds of norbornene, norbornadiene, and dispiroheptadiene to give the corresponding vinylcyclopropane adducts in yields up to 80%. 3,5-Dioxo-4-oxatricyclo[5.2.1. 0^2,6]dec-8-ene and 5-acetyl-7-oxabicyclo[2.2.1]hept-2-ene, which are heteroanalogs of dicyclopentadiene and norbornene, are inert relative to (I).Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 214–216, January, 1990.     

Novel heterocycles. 7. Reaction of 2-chloronicotinonitrile with thioureas. Synthesis of the pyrido[2,3-d]pyrimido-[2,1-b][1,3]thiazine ring system

N,N'-Dimethylthiourea and 3,4,5,6-tetrahydro-2-pyrimidinethiol were allowed to react with 2-chloro-nicotinonitrile ( 1 ) and their products investigated by standard methods and by carbon-13 nmr. In both instances, displacement of the chlorine occurred by nitrogen not the sulfur of the thioureas. Secondary cyclizations occurred by attack of nitrogen on the nitrile to furnish 3a , and by sulfur on the nitrile to give 4b , a new ring system. Tricyclic 4b was hydrolyzed in dilute acid to give 5 , or alkylated with methyl iodide in the presence of sodium hydride to give the ring opened product 6 .     

RAMPED-UP NMR: multiplexed NMR-based screening for drug discovery

The crucial step in drug discovery is the identification of a lead compound from a vast chemical library by any number of screening techniques. NMR-based screening has the advantage of directly detecting binding of a compound to the target. The spectra resulting from these screens can also be very complex and difficult to analyze, making this an inefficient process. We present here a method, RAMPED-UP NMR, (Rapid Analysis and Multiplexing of Experimentally Discriminated Uniquely Labeled Proteins using NMR) which generates simple spectra which are easy to interpret and allows several proteins to be screened simultaneously. In this method, the proteins to be screened are uniquely labeled with one amino acid type. There are several benefits derived from this unique labeling strategy: the spectra are greatly simplified, resonances that are most likely to be affected by binding are the only ones observed, and peaks that yield little or no information upon binding are eliminated, allowing the analysis of multiple proteins easily and simultaneously. We demonstrate the ability of three different proteins to be analyzed simultaneously for binding to two different ligands. This method will have significant impact in the use of NMR spectroscopy for both the lead generation and lead optimization phases of drug discovery by its ability to increase screening throughput and the ability to examine selectivity. To the best of our knowledge, this is the first time in any format that multiple proteins can be screened in one tube.     

Regioselective catalytic addition of terminal acetylenes to methyl esters of 1-alkylcyclopropene-3-carboxylic acids

Conclusions Terminal acetylenes and HCN in the presence of CuCl add regioselectively as CH-acids to the unsaturated three-membered ring of methyl esters of 1-alkylcyclopropene-3-carboxylic acids to form the methyl esters of the corresponding 3-alken-5-ynoic acids or 4-cyano-3-alkyl-3-butenoic acids in yields up to 60%.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2401–2405, October, 1985.These results were partially reported at the Seventh All-Union Conference on the Chemistry of Acetylene [1].     

Crystal and molecular structure of 1-aza-6′-(3′-oxo-5′, 5′-dimethyl-δ1′-pyrrolin-3′-yl)methylidene-2,2,7,7-tetramethyl-4-hydroxybicyclo-[2.2.21azaoctane

An x-ray structural study has shown that 6-(3-oxo-5,5-dimethyl-¹-pyrrolin-3-yl)methylidene-2,2,7, 7-tetramethyl-4-hydroxybicyclo[2.2.2]azaoctane is formed as a low-molecular-weight byproduct of the solid-phase polymerization of 1,4-bis(2,2,6,6-tetramethyl-4-hydroxy-4-piperidyl)butadiyne.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 585–587, March, 1990.     

Nucleic acid analysis using an expanded genetic alphabet to quench fluorescence

Organic chemistry has made possible the synthesis of molecules that expand on Nature's genetic alphabet. Using the previously described nonstandard DNA base pair constructed from isoguanine and 5-methylisocytosine, we report a highly specific and sensitive method that allows for the fast and specific quantitation of genetic sequences in a closed tube format. During PCR amplification, enzymatic site-specific incorporation of a quencher covalently linked to isoguanine allows for the simultaneous detection and identification of multiple targets. The specificity of method is then established by analysis of thermal denaturation or melting of the amplicons. The appropriate functions of all reactions are further verified by incorporation of an independent target into the reaction mixture. We report that the method is sensitive down to the single copy level, and specificity is demonstrated by multiplexed end-point genotypic analysis of four targets simultaneously using four separate fluorescent reporters. The method is general enough for quantitative and qualitative analysis of both RNA and DNA using previously developed primer sets. Though the method described employs the commonly used PCR, the enzymatic incorporation of reporter groups into DNA site-specifically should find broad utility throughout molecular biology.