Towards a green synthesis of isoquinoline: Beckmann rearrangement of E,-cinnamaldoxime over H-zeolites

Isoquinoline was prepared through the Beckmann rearrangement of cinnamaldoxime over different H-zeolites, K-10 montmorillonite clay, amorphous SiO2–Al2O3 and γ-alumina under well-optimized conditions of temperature, weight hourly space velocity and catalyst loading. Cinnamaldoxime under ambient reaction conditions over the catalysts underwent migration of the anti-styryl moiety to electron deficient nitrogen (Beckmann rearrangement) followed by an intramolecular cyclization to yield isoquinoline. Cinnamo-nitrile (dehydration product) and cinnamaldehyde were formed as by-products. Isoquinoline formation was high on zeolite catalysts (ca. >86.5%) and mordenite (ca. 92.3%) was the most efficient in the series. Catalysts were susceptible for deactivation and the decrease in the percentage conversion of oxime with time is associated with a corresponding increase in the acid hydrolysis producing salicylaldehyde at later stages of the reaction. However, these catalysts retain activity considerably and can be recycled without loss of activity and change of product distribution.

Evolution of domain combinations in protein kinases and its implications for functional diversity

Protein kinases phosphorylating Ser/Thr/Tyr residues in several cellular proteins exert tight control over their biological functions. They constitute the largest protein family in most eukaryotic species. Protein kinases classified based on sequence similarity in their catalytic domains, cluster into subfamilies, which share gross functional properties. Many protein kinases are associated or tethered covalently to domains that serve as adapter or regulatory modules,naiding substrate recruitment, specificity, and also serve as scaffolds. Hence the modular organisation of the protein kinases serves as guidelines to their functional and molecular properties. Analysis of genomic repertoires of protein kinases in eukaryotes have revealed wide spectrum of domain organisation across various subfamilies of kinases. Occurrence of organism-specific novel domain combinations suggests functional diversity achieved by protein kinases in order to regulate variety of biological processes. In addition, domain architecture of protein kinases revealed existence of hybrid protein kinase subfamilies and their emerging roles in the signaling of eukaryotic organisms. In this review we discuss the repertoire of non-kinase domains tethered to multi-domain kinases in the metazoans. Similarities and differences in the domain architectures of protein kinases in these organisms indicate conserved and unique features that are critical to functional specialization. (C) 2009 Elsevier Ltd. All rights reserved.

Peptide mimics for structural features in proteins. Crystal structures of three heptapeptide helices with a C-terminal 6-->1 hydrogen bond.

The crystal structure determination of three heptapeptides containing alpha-aminoisobutyryl (Aib) residues as a means of helix stabilization provides a high-resolution characterization of 6-->1 hydrogen-bonded conformations, reminiscent of helix-terminating structural features in proteins. The crystal parameters for the three peptides, Boc-Val-Aib-X-Aib-Ala-Aib-Y-OMe, where X and Y are Phe, Leu (I), Leu, Phe (II) and Leu, Leu (III) are: (I) space group P1, Z = 1, a = 9.903 A, b = 10.709 A, c = 11.969 A, alpha = 102.94 degrees, beta = 103.41 degrees, gamma = 92.72 degrees, R = 4.55%; (II) space group P21, Z = 2, a = 10.052 A, b = 17.653 A, c = 13.510 A, beta = 108.45 degrees, R = 4.49%; (III) space group P1, Z = 2 (two independent molecules IIIa and IIIb in the asymmetric unit), a = 10.833 A, b = 13.850 A, c = 16.928 A, alpha = 99.77 degrees, beta = 105.90 degrees, gamma = 90.64 degrees, R = 8.54%. In all cases the helices form 3(10)/alpha-helical (or 3(10)helical) structures, with helical columns formed by head-to-tail hydrogen bonding. The helices assemble in an all-parallel motif in crystals I and III and in an antiparallel motif in II. In the four crystallographically characterized molecules, I, II, IIIa and IIIb, Aib(6) adopts a left-handed helical (hL) conformation with positive phi, psi values, resulting in 6-->1 hydrogen-bond formation between Aib(2) CO and Leu(7)/Phe(7) NH groups. In addition a 4-->1 hydrogen bond is seen between Aib(3) CO and Aib(6) NH groups. This pattern of hydrogen bonding is often observed at the C-terminus of helices proteins, with the terminal pi-type turn being formed by four residues adopting the hRhRhRhL conformation.

Crystal structures of a nonapeptide helix containing alpha,alpha-di-n-butylglycine (Dbg), Boc-Gly-Dbg-Ala-Val-Ala-Leu-Aib-Val-Leu-OMe

Two crystals structures of a nonapeptide (anhydrous and hydrated) containing the amino acid residue alpha, alpha-di-n-butylglycyl, reveal a mixed 3(10)/alpha-helical conformation. Residues 1-7 adopt phi, psi values in the helical region, with Val(8) being appreciably distorted. The Dbg residue has phi, psi values of -40, -37 degrees and -46, -40 degrees in two crystals with the two butyl side chains mostly extended in each. Peptide molecules in the crystals pack into helical columns. The crystal parameters are C50H91N9O12, space group P2(1), with a = 9.789(1) Angstrom, b = 20.240(2) Angstrom, c = 15.998(3) Angstrom, beta = 103.27(1); Z = 2, R = 10.3% for 1945 data observed >3 sigma(F) and C50H91N9O12. 3H(2)O, space group P2(1), with a = 9.747(3) Angstrom, b = 21.002(8) Angstrom, c = 15.885(6) Angstrom, beta = 102.22(3)degrees, Z = 2, R = 13.6% for 2535 data observed >3 sigma(F). The observation of a helical conformation at Dbg suggests that the higher homologs in the alpha, alpha-dialkylated glycine series also have a tendency to stabilize peptide helices. (C) Munksgaard 1996.

Stochastic simulations of the origins and implications of long-tailed distributions in gene expression

Gene expression noise results in protein number distributions ranging from long-tailed to Gaussian. We show how long-tailed distributions arise from a stochastic model of the constituent chemical reactions and suggest that, in conjunction with cooperative switches, they lead to more sensitive selection of a subpopulation of cells with high protein number than is possible with Gaussian distributions. Single-cell-tracking experiments are presented to validate some of the assumptions of the stochastic simulations. We also examine the effect of DNA looping on the shape of protein distributions. We further show that when switches are incorporated in the regulation of a gene via a feedback loop, the distributions can become bimodal. This might explain the bimodal distribution of certain morphogens during early embryogenesis.

Correlation of thermodynamic properties of chloromethanes

A correlation for entropy and enthalpy based on the two-parameter law of corresponding states and the reference substance concept has been obtained. For 199 points tested, the over-all average absolute deviation and the maximum deviations in the calculated values of entropy with the available data are 0.74 and 7.20%. The corresponding deviations of enthalpy are 1.86 and 15.0%, respectively. A compressibility chart for chloromethanes has been made and shown to be superior to existing charts. For 102 points tested, the average absolute and maximum deviations in the compressibilities were 1.80 and 19.5%, respectively.

High levels of catalytic antibodies correlate with favorable outcome in sepsis

Sepsis is the leading cause of death in intensive care units and results from a deleterious systemic host response to infection. Although initially perceived as potentially deleterious, catalytic antibodies have been proposed to participate in removal of metabolic wastes and protection against infection. Here we show that the presence in plasma of IgG endowed with serine protease-like hydrolytic activity strongly correlates with survival from sepsis. Variances of catalytic rates of IgG were greater in the case of patients with severe sepsis than healthy donors (P < 0.001), indicating that sepsis is associated with alterations in plasma levels of hydrolytic IgG. The catalytic rates of IgG from patients who survived were significantly greater than those of IgG from deceased patients (P < 0.05). The cumulative rate of survival was higher among patients exhibiting high rates of IgG-mediated hydrolysis as compared with patients with low hydrolytic rates (P < 0.05). An inverse correlation was also observed between the markers of severity of disseminated intravascular coagulation and rates of hydrolysis of patients' IgG. Furthermore, IgG from three surviving patients hydrolyzed factor VIII, one of which also hydrolyzed factor IX, suggesting that, in some patients, catalytic IgG may participate in the control of disseminated microvascular thrombosis. Our observations provide the first evidence that hydrolytic antibodies might play a role in recovery from a disease.

Determination of the orthotropic plate parameters of stiffened plates and grillages in free vibration

It is well known that the analysis of vibration of orthogonally stiffened rectangular plates and grillages may be simplified by replacing the actual structure by an orthotropic plate. This needs a suitable determination of the four elastic rigidity constants Dx, Dy, Dxy, D1 and the mass {Mathematical expression} of the orthotropic plate. A method is developed here for determining these parameters in terms of the sectional properties of the original plate-stiffener combination or the system of interconnected beams. Results of experimental work conducted on aluminium plates agree well with the results of the theory developed here.

The Raman spectrum of cyclohexanol

The Raman spectrum of cyclohexanol has been studied in detail in the liquid state at 30° C. and at about 68° C. and in the solid state at about 13° C. The O-H stretching frequency of cyclohexanol has been found to extend from 3106-3571 cm.-1 in the liquid state at 30° C. and from 3204-3652 cm.-1 at 68° C. The 38 lines recorded in the present investigation have been following frequency shifts: 342, 408, 458, 478, 555, 653, 789, 834, 843, 863, 887, 920, 966, 978, 1024, 1047, 1070, 1139, 1173, 1184, 1210, 1235, 1252, 1301, 1329, 1346, 1362, 1438, 1448, 1464, 2660, 2684, 2710, 2854, 2896, 2925, 2940, 3106 to 3511 (band). Those lines which are italicized are the additional lines observed for the first time. The Raman lines at 966 cm.-1 and 1070 cm.-1 have been assigned to C-OH stretching vibrations of the axial and equatorial isomers. The ratio of the integrated intensity of the 1070 cm.-1 line to the 966 cm.-1 gave the equilibrium constant K as 2·896 at 30° C. and as 2·66 at 68° C. Knowing K, the free energy different Δ F was calculated and it was found to be 0·64 Kcal./mole at 30° C. and 0·66 Kcal./mole at about 68° C. Reasonable assignment has been made for most of the observed Raman lines.

A preliminary survey of dermatomycoses in Bangalore

Clinical and mycological investigations were made on 225 cases of suspected dermatomycoses. Of these, 102 were microscopically positive. But only 63 were culturally positive, and these are analysed here with regard to clinical patterns and aetiological species, age, sex and occupational incidence and susceptibility to griseofulvin in vitro. As in most other parts of India, Trichophyton rubrum was the dominant species. A high proportion of Epidermophyton floccosum was an unusual feature seen. Of the clinical types, tinea cruris was the most common. The isolates were sensitive to griseofulvin at low concentrations of 1 to 5 μg per ml of agar medium, E. floccosum being the most sensitive.

Genetic characterization of Indian type O FMD virus 3A region in context with host cell preference

The 3A region of foot-and-mouth disease virus has been implicated in host range and virulence. For example, amino acid deletions in the porcinophilic strain (O/TAW/97) at 93-102 aa of the 153 codons long 3A protein have been recognized as the determinant of species specificity. In the present study, 18 type 0 FMDV isolates from India were adapted in different cell culture systems and the 3A sequence was analyzed. These isolates had complete 3A coding sequence (153 aa) and did not exhibit growth restriction in cells based on species of origin. The 3A region was found to be highly conserved at N-terminal half (1-75 aa) but exhibited variability or substitutions towards C-terminal region (80-153). Moreover the amino acid substitutions were more frequent in recent Indian buffalo isolates but none of the Indian isolates showed deletion in 3A protein, which may be the reason for the absence of host specificity in vitro. Further inclusive analysis of 3A region will reveal interesting facts about the variability of FMD virus 3A region in an endemic environment. (C) 2010 Elsevier B.V. All rights reserved.

A new method of producing local enhancement of buoyancy in liquid flows

We describe here a novel method of generating large volumetric heating in a liquid. The method uses the principle of ohmic heating of the liquid, rendered electrically conducting by suitable additives if necessary. Electrolysis is prevented by the use of high frequency alternating voltage and chemically treated electrodes. The technique is demonstrated by producing substantial heating in an initially neutral jet of water. Simple flow visualisation studies, made by adding dye to the jet, show marked changes in the growth and development of the jet with heat addition.