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.     

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.     

QUENCHING OF METHYLCYCLOHEXANE FLUORESCENCE BY METHANOL*

We measured the fluorescence emission spectrum and intensity decays of methylcyclohexane (MCH) when excited by simultaneous absorption of two photons at 298 nm. The steady-state intensities and lifetimes were both decreased by methanol, which was found to be an efficient quencher of MCH fluorescence. Methanol quenching of MCH is clearly dynamic, but the exact mechanism of quenching is unclear. Dynamic quenching of MCH was also observed by water and n-propanol. These results suggest that alkane fluorescence from biopolymers, if observable, will only occur from regions of the macromolecules that are not exposed to water.     

Separation of Trp-Arg and Arg-Trp using G-quartet-forming DNA oligonucleotides in open-tubular capillary electrochromatography

DNA oligonucleotides that form intramolecular G-quartet structures were investigated as stationary phase reagents for separation of mixtures of the isomeric dipeptides Trp-Arg and Arg-Trp in open-tubular capillary electrochromatography (OTCEC). The oligonucleotides included a thrombin-binding aptamer that forms a biplanar G-quartet structure and an oligonucleotide that forms a 4-plane G-quartet structure. Fluorescence, circular dichroism and UV-visible absorbance spectroscopies were used in batch solution studies to indicate interactions between the dipeptides and the biplanar G-quartet structure. Results for OTCEC separations were compared with results obtained for capillary zone electrophoresis separations on a bare capillary. Temperature studies suggest that resolution is improved when the G-quartet structure is partially destabilized, but control experiments in which potassium chloride was not included in the mobile phase indicate that the G-quartet structure nevertheless plays a role in the separations.     

The oscillation frequency of a quartz resonator in contact with liquid

A simple relationship is derived which expresses the change in oscillation frequency of a quartz crystal in contact with a fluid in terms of material parameters of the fluid and the quartz. The relationship is Δf = ?f^{$\text{3}\text{2}$}₀(η_L?_L/πμ_Q?_Q)^{$\text{1}\text{2}$}, where f₀ is the oscillation frequency of the free (dry) crystal, η_L and ?_L are the absolute viscosity and density of the liquid, respectively, and μ_Q and ?_Q are the elastic modulus and density of the quartz. This relation is obtained from a simple physical model which couples the shear wave in the quartz to a damped shear wave in the fluid. Quantitative comparisons with two test cases, aqueous solutions of glucose and ethanol at various concentrations, demonstrate the accuracy of this model.