An efficient preparation of isosteric phosphonate analogues of sphingolipids by opening of oxirane and cyclic sulfamidate intermediates with alpha-lithiated alkylphosphonic esters

D-erythro-(2S,3R,4E)-Sphingosine-1-phosphonate (1), the isosteric phosphonate analogue of naturally occurring sphingosine 1-phosphate (1a), and D-ribo-phytosphingosine 1-phosphonate (2), the isosteric phosphonate analogue of D-ribo-phytosphingosine-1-phosphate (2a), were synthesized starting with methyl 2,3-O-isopropylidene-d-glycerate (4) and D-ribo-phytosphingosine (3), respectively. Oxirane 12 was formed in eight steps from 4, and cyclic sulfamidate 22 was formed in five steps from 3. The phosphonate group was introduced via regioselective ring-opening reactions of oxirane 12 and cyclic sulfamidate 22 with lithium dialkyl methylphosphonate, affording 13 and 23, respectively. The synthesis of 1 was completed by S(N)2 displacement of chloromesylate intermediate 14b with azide ion, followed by conversion of the resulting azido group to a NHBoc group and deprotection. The synthesis of 2 was completed by cleavage of the acetal, N-benzyl, and alkyl phosphonate ester groups.     

Calculation of the 1J(PP) angular dependence in P2H4

Using the results obtained from an MO SCF ab initio calculation on P₂H₄ in four different conformations, the ¹J(PP) NMR coupling constants have been calculated. The ¹J(PP) values are highly dependent upon the rotational angle φ (?238.0 Hz in the eclipsed conformation, 10.9 Hz in the staggered one). The shape of the theoretical ¹J(PP) plot seems to be in good agreement with experimentally measured ¹J(PP) values.     

Characterization of dynamic and steady-state protein phosphorylation using a fluorescent phosphoprotein gel stain and mass spectrometry

Protein phosphorylation plays a vital role in the regulation of most aspects of cellular activity, being key to propagating messages within signal transduction pathways and to modulating protein function. Pro-Q Diamond phosphoprotein gel stain is suitable for the fluorescence detection of phosphoserine-, phosphothreonine-, and phosphotyrosine-containing proteins directly in sodium dodecyl sulfate (SDS)-polyacrylamide gels. The technology is especially appropriate for profiling steady-state and dynamic phosphorylation on a proteome-wide scale, as demonstrated through detection of the native phosphorylation of cardiac mitochondrial phosphoproteins and changes in this profile arising from the activity of a protein kinase. For example, Pro-Q Diamond phosphoprotein gel stain was employed to demonstrate that among the 46 subunits of the mitochondrial respiratory chain complex, NADH:ubiquinone oxidoreductase (complex I), a 42 kDa subunit is phosphorylated in the steady-state. However, exposure of mitochondria to cAMP-dependent protein kinase increases phosphorylation of this 42 kDa subunit and results in de novo phosphorylation of an 18 kDa subunit as well. Since Pro-Q Diamond dye binds to phosphorylated residues noncovalently, the staining technology is fully compatible with modern microchemical analysis procedures, such as peptide mass profiling by matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and post-source decay analysis of peptide phosphorylation.     

Conformational changes accompanying electronic excitation of CD3 NO

Analysis of the 675 nm absorption of CD₃NO shows that the conformation changes from eclipsed in the ground state to staggered in the à ¹A″(ne*) excited state. The internal-rotation barrier V₃ increases from 383 to 475± 50 cm^?1.     

Bistable ferroelectric liquid crystal photoswitch triggered by a dithienylethene dopant

The spontaneous polarization (PS) of a ferroelectric liquid crystal is modulated reversibly by photocyclization of the dopant 1,2-bis[5'-(4' '-heptyloxyphenyl)-2'-methylthien-3'-yl]perfluorocyclopentene. The magnitude of PS photomodulation increases with dopant concentration up to 3 mol %, and the resulting photoswitch is fatigue resistant and bistable. To the best of our knowledge, this is the first example of a bistable ferroelectric liquid crystal photoswitch to be reported in the literature.     

Diverse redox-active molecules bearing O-, S-, or Se-terminated tethers for attachment to silicon in studies of molecular information storage

A molecular approach to information storage employs redox-active molecules tethered to an electroactive surface. Attachment of the molecules to electroactive surfaces requires control over the nature of the tether (linker and surface attachment group). We have synthesized a collection of redox-active molecules bearing different linkers and surface anchor groups in free or protected form (hydroxy, mercapto, S-acetylthio, and Se-acetylseleno) for attachment to surfaces such as silicon, germanium, and gold. The molecules exhibit a number of cationic oxidation states, including one (ferrocene), two [zinc(II)porphyrin], three [cobalt(II)porphyrin], or four (lanthanide triple-decker sandwich compound). Electrochemical studies of monolayers of a variety of the redox-active molecules attached to Si(100) electrodes indicate that molecules exhibit a regular mode of attachment (via a Si-X bond, X = O, S, or Se), relatively homogeneous surface organization, and robust reversible electrochemical behavior. The acetyl protecting group undergoes cleavage during the surface deposition process, enabling attachment to silicon via thio or seleno groups without handling free thiols or selenols.     

A rapid access to chiral alkylidene cyclopentenone prostaglandins involving ring-closing metathesis reaction

A synthesis of the alkylidene cyclopentenone prostaglandin TEI 9826 has been realized. The synthesis involved the preparation of the chiral 1,5-diene 8 using a stereoselective Claisen rearrangement from the allylic alcohol 6 giving the ester 7 after vinylation. Then a key RCM reaction allowed the preparation of the cyclopentenol 9 which, after oxidation, gave the cyclopentenone 10, precursor of the prostaglandin.     

Unsymmetrical selenides from selenocyanates and methyl grignard

The addition of methyl Grignard to diethyl acetamido(cyanoselenobenzyl)malonates 3 and 4 at ?78° followed by hydrolysis yields the 3-(4-and 3-methylselenophenyl)alanines 1 and 2.     

Potentiometric response of graphite electrodes coated with modified polymer films

Graphite electrodes coated with chemically-modified polymer films are described. Several different polymers were used, including poly(acrylic acid), poly[triethyl(vinylbenzyl)ammonium chloride], poly[trihexyl(vinylbenzyl)ammonium chloride], and poly[trihexyl(vinylbenzyl)ammonium thiocyanate]. A cation-responsive electrode can be prepared from poly(acrylic acid)-coated graphite. Anion-responsive electrodes can be prepared from graphite coated with polymeric quaternary amines. In these electrodes, the ion-sensing species is irreversibly attached to the polymer (rather than physically entrapped within a polymer matrix); this factor eliminates leaching of the active component, and the addition of a plasticizer is unnecessary. A selective sensor for thiocyanate is described; it yields a Nernstian response over the concentration range 1 × 10^?1–1 × 10^?5 M sodium thiocyanate.     

Application of parallel processing techniques to improving the efficiency of MM2 molecular mechanics calculations

The application of parallel processing techniques to molecular mechanics calculations is evaluated. Using the standard molecular mechanics package, MM2, four different parallel versions of the program are implemented in a four-processor computing environment. A set of 529 test structures is used to compare the efficiency of the parallel versions of MM2 to a standard serial version of the program. Statistics describing execution times and program execution cycles are gathered and analyzed. The effects of parallel processing overhead and computer system load are explored, and the practical utility of parallel processing in molecular mechanics is estimated. The results of these parallelization experiments indicate that for geometry optimizations requiring significant amounts of computing time an improvement in program execution speed approaching 50% is realizable. © 1993 John Wiley & Sons, Inc.