Phytol-based novel adjuvants in vaccine formulation: 2. assessment of efficacy in the induction of protective immune responses to lethal bacterial infections in mice

Background  

Adjuvants are known to significantly enhance vaccine efficacy. However, commercial adjuvants often have limited use because of toxicity in humans. The objective of this study was to determine the comparative effectiveness of a diterpene alcohol, phyto l and its hydrogenated derivative PHIS-01, relative to incomplete Freund's adjuvant (IFA), a commonly used adjuvant in augmenting protective immunity in mice against E. coli and S. aureus, and in terms of inflammatory cytokines.     

Stochastic Games with Average Payoff Criterion

We study two-person stochastic games on a Polish state and compact action spaces and with average payoff criterion under a certain ergodicity condition. For the zero-sum game we establish the existence of a value and stationary optimal strategies for both players. For the nonzero-sum case the existence of Nash equilibrium in stationary strategies is established under certain separability conditions. Accepted 9 January 1997     

Mutual-diffusion of some transition metal halides

The diffusion of some zinc and cobalt salts in water have been measured using an improved version of the capillary technique. In this technique, diffusion proceeds in the absence of stirring in the bulk solution. The amount of diffusing substance which remains in the capillary is analyzed after a chosen time. Nanis' solution for three-dimensional diffusion from a capillary has been used to calculate the experimental values. The values of diffusion coefficient of zinc iodide, cobalt bromide and cobalt iodide have been obtained with a diffusion run time of four hours. A comparison has been made between the experimental and theoretical values obtained from Onsager-Fuoss theory. An attempt has also been made to explain the deviation between the experimental and theoretical values over the concentration range studied.     

An experimental investigation on impact response of laminated composite beams

Experiments based on a new technique were carried out to study the response of glass/epoxy laminated composite beams subjected to impact loading. A number of glass/epoxy composite beams with different fiber orientations, spans, thicknesses, and support conditions were impacted with an instrumented impact hammer and the responses were picked up using an accelerometer in conjunction with a spectrum analyzer. Free vibration test for some sample beams were also carried out to determine their fundamental frequencies.     

Attachment of 4-methoxy benzyl units to a tripodal fluoroionophore shows reversal of output functionality with Cu(II) input

Syntheses of three tris-(2-aminoethyl)amine, tren based tripodal fluoroionophores (L₂, L₃, and L₅), are reported. These fluoroionophores are designed based on the fluorophore–spacer–receptor format (choice of fluorophore in all three cases is anthryl unit). In L₂, three anthracene moieties are attached to the three arms of tren via –CH₂-spacer whereas L₃ and L₅ have p-nitro benzyl and p-methoxy benzyl substitutions, respectively, on L₂, which are in close proximity to the photoinduced electron transfer (PET) center. All three fluoroionophores show appreciably lower fluorescence compared to anthracene due to effective PET process in these systems but the quantum yield varies depending upon the nature of substitution at the PET center. In the cases of L₂ and L₅ different amounts of fluorescence recovery are observed in the presence of different cation inputs whereas L₃ is almost inactive toward cation sensing. Detailed fluorescence emission studies on L₂ and L₅ in the presence of different cation inputs showed that L₅ having N4 donor sets bearing three p-methoxy benzyl units attached to the three nitrogen centers involving photoinduced electron transfer process is a viable candidate for enhancement of fluorescence with Cu(II) input. In the absence of p-methoxy benzyl units at the nitrogen centers' resulting system, L₂ shows quenching of fluorescence with the Cu(II) under same experimental conditions.     

Ultrafast intermolecular hydrogen bond dynamics in the excited state of fluorenone

Steady-state fluorescence and time-resolved absorption measurements in pico- and femtosecond time domain have been used to investigate the dynamics of hydrogen bond in the excited singlet (S(1)) state of fluorenone in alcoholic solvents. A comparison of the features of the steady-state fluorescence spectra of fluorenone in various kinds of media demonstrates that two spectroscopically distinct forms of fluorenone in the S(1) state, namely the non-hydrogen-bonded (or free) molecule as well as the hydrogen-bonded complex, are responsible for the dual-fluorescence behavior of fluorenone in solutions of normal alcoholic solvents at room temperature (298 K). However, in 2,2,2-trifluoroethanol (TFE), a strong hydrogen bond donating solvent, emission from only the hydrogen-bonded complex is observed. Significant differences have also been observed in the temporal evolution of the absorption spectroscopic properties of the S(1) state of fluorenone in protic and aprotic solvents following photoexcitation using 400 nm laser pulses. An ultrafast component representing the solvent-induced vibrational energy relaxation (VER) process has been associated with the dynamics of the S(1) state of fluorenone in all kinds of solvents. However, in protic solvents, in addition to the VER process, further evolution of the spectroscopic and dynamical properties of the S(1) state have been observed because of repositioning of the hydrogen bonds around the carbonyl group. In normal alcohols, two different kinds of hydrogen-bonded complex of the fluorenone-alcohol system with different orientations of the hydrogen bond with respect to the carbonyl group and the molecular plane of fluorenone have been predicted. On the other hand, in TFE, formation of only one kind of hydrogen-bonded complex has been observed. These observations have been supported by theoretical calculations of the geometries of the hydrogen-bonded complexes in the ground and the excited states of fluorenone. Linear correlation between the lifetimes of the equilibration process occurring because of repositioning of the hydrogen bonds and Debye or longitudinal relaxation times of the normal alcoholic solvents establish the fact that, in weakly hydrogen bond donating solvents, the hydrogen bond dynamics can be described as merely a solvation process. Whereas, in TFE, hydrogen bond dynamics is better described by a process of conversion between two distinct excited states, namely, the non-hydrogen-bonded form and the hydrogen-bonded complex.     

Intermolecular electron transfer between coumarin dyes and aromatic amines in Triton-X-100 micellar solutions: evidence for Marcus inverted region

Photoinduced electron transfer (ET) between coumarin dyes and aromatic amines has been investigated in Triton-X-100 micellar solutions and the results have been compared with those observed earlier in homogeneous medium. Significant static quenching of the coumarin fluorescence due to the presence of high concentration of amines around the coumarin fluorophore in the micelles has been observed in steady-state fluorescence studies. Time-resolved studies with nanosecond resolutions mostly show the dynamic part of the quenching for the excited coumarin dyes by the amine quenchers. A correlation of the quenching rate constants, estimated from the time-resolved measurements, with the free energy changes (DeltaG0) of the ET reactions shows the typical bell shaped curve as predicted by Marcus outer-sphere ET theory. The inversion in the ET rates for the present systems occurs at an exergonicity (-DeltaG0) of approximately 0.7-0.8 eV, which is unusually low considering the polarity of the Palisade layer of the micelles where the reactants reside. Present results have been rationalized on the basis of the two dimensional ET model assuming that the solvent relaxation in micellar media is much slower than the rate of the ET process. Detailed analysis of the experimental data shows that the diffusional model of the bimolecular quenching kinetics is not applicable for the ET reactions in the micellar solutions. In the present systems, the reactions can be better visualized as equivalent to intramolecular electron transfer processes, with statistical distribution of the donors and acceptors in the micelles. A low electron coupling (Vel) parameter is estimated from the correlation of the experimentally observed and the theoretically calculated ET rates, which indicates that the average donor--acceptor separation in the micellar ET reactions is substantially larger than for the donor--acceptor contact distance. Comparison of the Vel values in the micellar solution and in the donor--acceptor close contact suggests that there is an intervention of a surfactant chain between the interacting donor and acceptor in the micellar ET reaction.     

An efficient strategy for N-alkylation of benzimidazoles/imidazoles in SDS-aqueous basic medium and N-alkylation induced ring opening of benzimidazoles

A sustainable route for the N-1 alkylation of imidazole and benzimidazole derivatives has been developed under volatile organic solvent free condition in alkaline water-SDS system. Incorporation of SDS in the reaction medium enhances the reaction rate by suppressing the solubility issue that arises for different substrates. This method provides high yield of the alkylated product in a shorter reaction time. For reactive alkyl halides reaction proceeds at ambient temperature whereas in the cases of less reactive alkyl halides require 55–60?°C to complete alkylation process. N-alkylation induced ring opening of the heterocyclic ring in benzimidazole derivatives to multifunctional aromatic compounds were noticed at 60?°C when more than two equivalents of alkyl halide was used.     

Influence of <Emphasis Type="Italic">gauche</Emphasis> effect on uncharged oxime reactivators for the reactivation of tabun-inhibited AChE: quantum chemical and steered molecular dynamics studies

The neutral oxime reactivator RS194B with a seven-membered ring has shown better efficacy towards the tabun-inhibited AChE than that of RS69N with a six-membered ring and RS41A with a five-membered ring. The difference in the efficacy of these reactivators has remained unexplored. We report here the origin of the difference of efficacy of these reactivators based on the conformational analysis, quantum chemical calculations and steered molecular dynamics (SMD) simulations. The conformational analysis using B3LYP/6-31G(d) level of theory revealed that RS41A and RS194B are more stable in gauche conformation due to the gauche effect (–N–C–C–N– bonds) whereas RS69N prefers anti-conformation. The SMD simulations show that RS194B retains in more stable gauche conformation inside the active gorge of AChE during different time intervals that experiences more hydrogen bonding, hydrophobic interactions with the catalytic anionic site (CAS) residues and weaker interactions with the peripheral anionic site (PAS) residues compared to RS41A and RS69N. In an effort to design an even superior reactivator, RS194B-S has been chosen with a subtle change in the geometry of RS194B by replacing the carbonyl oxygen with the sulfur atom. The newly designed reactivator RS194B-S can also be a promising candidate to reactivate tabun-inhibited AChE.