The reaction of pyrroles with trimethylhalosilanes-dialkyl sulfoxides

Pyrroles are powerful nucleophiles in the reaction with dialkyl sulfoxides and trimethylchlorosilane (TMCS) or trimethylbromosilane (TMBS), affording sulfonium salts or halo derivatives, generally in good yields.     

On the choice of active space orbitals in MCSCF calculations

We describe a procedure which may be used to aid selection of the active space in multiconfigurational self-consistent field (MCSCF) calculations for general chemical systems. Starting from a restricted Hartree-Fock calculation, we define a hierarchy of interacting virtual orbitals for every occupied orbital. The most strongly interacting orbitals are then taken to constitute the active space in a configuration interaction (CI) calculation. The natural orbital occupation numbers obtained from the CI calculation are then used to choose the active space to be used in a subsequent MCSCF calculation. We illustrate our method on a number of systems (Li₂, B₂, C₂, carbonyl oxide and the transition state for oxidation of H₂S by dioxirane). In all these cases, ‘intuitive’ active spaces are inadequate, as are active spaces derived from the natural orbitals of unrestricted Hartree-Fock calculations.     

New synthetic approaches to 3-carhoxamides of 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide

Two new synthetic approaches to the title compounds are reported. In the first of these, starting with N-carbobenzyloxysarcosine, four synthetic steps are employed to finally assemble the C³? C⁴ bond of the 1,2-benzothiazine ring. In the second approach, an enol ether is employed as a protecting group to allow formation of the 3-carboxamide function, which is followed by cleavage of the ether function to yield the desired 4-hydroxy-1,2-benzothiazine-3-carboxamide 1,1-dioxide.     

Synthesis of enzyme-inhibitory phospholipid analogs II. Preparation of chiral 1-acyl-2-acylamido-2-deoxyglycerophosphorycholines from serine

A facile and efficient stereospecific route to the enzyme-inhibitory 2-amide analogs of phosphatidycholine is reported.     

Monte Carlo simulation of water solvent with biomolecules: Serine and the corresponding zwitterion

Monte Carlo simulation results are reported for clusters consisting of 250 water molecules surrounding serine, both in the neutral form and in two zwitterionic conformers (in order to gain some insight into conformational effects). Calculations were carried out at 300 K and using two-body potentials obtained by means of quantum-mechanical calculations. The spatial dependence of the average interaction energies was investigated. The solvation structure was investigated by means of radial distribution functions and probability density maps, which showed a few water molecules directly solvating the hydrophilic groups and, beyond them, a more or less rich and complex hydrogen-bonded network of solvent molecules.     

Vesicle adsorption and lipid bilayer formation on glass studied by atomic force microscopy

The adsorption of phosphatidylcholine (PC) vesicles (30, 50, and 100 nm nominal diameters) and of dye-labeled PC vesicles (labeled with 6% Texas Red fluorophore (TR) and encapsulated carboxy fluorescein (CF)) to glass surfaces was studied by contact mode atomic force microscopy in aqueous buffer. These studies were performed in part to unravel details of the previously observed isolated rupture of dye-labeled PC vesicles on glass (Johnson, J. M.; Ha, T.; Chu, S.; Boxer, S. G. Biophys. J. 2002, 83, 3371-3379), specifically to differentiate partial rupture, that is, pore formation and leakage of entrapped dye, from full rupture to form bilayer disks. In addition, the adhesion potential of PC vesicles on glass was calculated based upon the adhesion-driven flattening of adsorbed vesicles and a newly developed theoretical model. The vesicles were found to flatten considerably upon adsorption to glass (width-to-height ratio of approximately 5), which leads to an estimate for the adhesion potential and for the critical rupture radius of 1.5 x 10(-4) J/m2 and 250 nm, respectively. Independent of vesicle size and loading with dye molecules, the adsorption of intact vesicles was observed at all concentrations below a threshold concentration, above which the formation of smooth lipid bilayers occurred. In conjunction with previous work (Johnson, J. M.; Ha, T.; Chu, S.; Boxer, S. G. Biophys. J. 2002, 83, 3371-3379), these data show that 6% TR 20 mM CF vesicles adsorb to the surface intact but undergo partial rupture in which they exchange content with the external buffer.     

The chemistry of fluorine containing phosphaalkenes, arsaalkenes and selenocarbonyls

This review covers our extensive research activities in the area of fluorine containing phospha- and arsaalkenes as well as selenocarbonyls, which differ considerably in their properties and reactivities from their alkyl and aryl counterparts and thus contribute in a gratifying manner to the still growing field of unsaturated element-carbon compounds of 3rd and 4th row main group elements E. Of particular interest is the influence of the fluorine substituents and other small groups (OR, NR₂) with either inductive and/or mesomeric effects on the polarity and reactivity of the EC bond. Addition reactions of proton acidic and hydridic polar HX reactants as well as [2+2], [3+2] and [4+2] cycloadditions have been thoroughly studied. The results obtained allow a classification of the EC systems within five different types, A to E, and prove a change from “normal” to “inverse” heteroalkenes in this sequence. The ligand properties of some derivatives have also been investigated in some detail.     

LETTUCE SEED GERMINATION: EFFECTS OF HIGH TEMPERATURE AND OF REPEATED FAR-RED TREATMENT IN RELATION TO PHYTOCHROME

Abstract— At 37°C the active form of phytochrome in lettuce seed cannot function to promote subsequent germination. This effect of high temperature is distinct from thermal acceleration of dark reversion from the active form of phytochrome to the inactive form, and may be due to reversible denaturation of phytochrome.
Repeated brief irradiations with far-red light inhibit subsequent germination in the whole seed, whereas a similar irradiation regime results in a strong enhancement of the development of growth potential (ability to expand against an externally-imposed osmotic restraint) in the excised axial portion of the seed. A possible explanation for these two opposing results, in volving two different pigment systems with effective loci in different parts of the seed, is suggested.     

Thiophene and butadiene-thiolate complexes of molybdenum: observations relevant to the mechanism of hydrodesulfurization

Mo(PMe3)6 reacts with thiophene to give the eta5-thiophene complex (eta5-C4H4S)Mo(PMe3)3 and the eta5-butadiene-thiolate complex (eta5-C4H5S)Mo(PMe3)2(eta2-CH2PMe2), which are the first examples of (i) eta5-thiophene coordination and (ii) C-S cleavage and hydrogenation by a molybdenum compound. Deuterium labeling studies suggest that the hydrogenation of thiophene may involve an alkylidene intermediate, an observation that has ramifications for the mechanisms of hydrodesulfurization.     

Calculating similarities between biological activities in the MDL Drug Data Report database

There are a number of licensed databases that assign biological activities to druglike compounds. The MDL Drug Data Report (MDDR), compiled from the patent literature, is a popular example. It contains several hundred distinct activities, some of which are therapeutic areas (e.g., Antihypertensive) and some of which are related to specific enzymes or receptors (e.g., ACE inhibitor). There are several data mining applications where it would be useful to calculate a similarity between any two activities. Two distinct activity labels can have a significant similarity for a number of reasons: two activities can be nearly synonymous (e.g., CCK B antagonist vs Gastrin antagonist), one activity may be a subset of another (e.g., Dopamine (D2) agonist vs Dopamine agonist), or an activity can be the mechanism by which another activity works (e.g., ACE inhibitor vs Antihypertensive), etc. In an ideal world, similarities for two activities could be calculated simply by comparing the compounds they have in common, but in hand-curated databases such as the MDDR the assignment of activities to compounds are inevitably inconsistent and incomplete. We propose a number of methods of calculating activity-activity similarities that hopefully compensate for errors in hand-curation. Two of these, TIMI and trend vector, show promise. Soft clustering of the activities using a union of similarity methods shows a reasonable association of therapeutic areas with their mechanisms.