A new nonpeptide tachykinin NK1 receptor antagonist isolated from the plants of Compositae

To find new tachykinin NK1 receptor antagonists from natural sources, we examined the tachykinin antagonist activity in the extracts of approximately 200 species of plants by the use of isolated guinea pig ileum. As a result, we discovered a novel and potent NK1 receptor antagonist in the extract of dried flowers of Matricaria chamomilla L. (chamomile). The structure of the antagonist was established as N1,N5,N10,N14-tetrakis[3-(4-hydroxyphenyl)-2-propenoyl]-1,5,10,14-tetraazatetradecane (tetracoumaroyl spermine, 1a). The Ki values of 1a, estimated from the inhibitory action on the substance P (SP)-induced contraction of the guinea pig ileum and the inhibition of the binding of [3H][Sar9, Met(O2)11]SP to human NK1 receptors, were 21.9 nM and 3.3 nM, respectively. 1a is the first potent NK1 receptor antagonist from natural sources and it has a unique structure of a polyacylated spermine. 1a was concentrated in pollen of Matricaria chamomilla L. and was also found in the extracts of flowers of other four species of Compositae. In addition, we found N1,N5,N10-tris[3-(4-hydroxyphenyl)-2-propenoyl]-1,5,10,14-tetraazatetradecane (2) as a new compound in the extract of flowers of Matricaria chamomilla L., which did not exhibit any tachykinin antagonist activity. A number of related compounds were synthesized, and the structure-activity relationship was studied.     

Two New Regulatory Properties Arising from the Transient Phase Kinetics of Monocyclic Enzyme Cascades

Taking as starting point a previous contribution about the kinetics of the transient phase and steady-state of monocyclic enzyme cascades, this paper suggest the definition and use of new regulatory modification properties involving the time elapses from the onset of the reaction to the attainment of the steady-state for a monocyclic enzyme cascade. A minimal set of simplifying assumptions allowing to derive analytical expressions for these properties has been used. From these general expressions we derive, as particular cases, other simpler expressions by using additional assumptions which have, therefore, a smaller range of validity. A discussion of the relationships between the kinetic parameters and concentrations needed to the additional assumption is observed is carried out. The goodness of our analysis has been tested by using numerical integration of the set of differential equation describing the kinetic behaviour of the cascade. The results obtained for a type of cascade are extrapolable to other different schemes of monocyclic enzyme cascades. Finally, a kinetic data analysis and an experimental design are suggested     

Understanding the Reactivity of Planar Polycyclic Aromatic Hydrocarbons: Towards the Graphene Limit

The Diels–Alder reactivity of maleic anhydride towards the bay regions of planar polycyclic aromatic hydrocarbons was explored computationally in the DFT framework. The process becomes more and more exothermic and the associated activation barriers become lower and lower when the size of the system increases. This enhanced reactivity follows an exponential behavior that reaches its maximum for systems having 18–20 benzenoid rings in their structures. This peculiar behavior was analyzed in detail by using the activation strain model of reactivity in combination with energy decomposition analysis. The influence of the change in the aromaticity of the polycyclic compound during the process on the respective activation barriers was also studied.     

Reactivity and Selectivity of Bowl‐Shaped Polycyclic Aromatic Hydrocarbons: Relationship to C60

The Diels–Alder reactivity of different bowl‐shaped polycyclic aromatic hydrocarbons (namely, corannulene, cyclopentacorannulene, diindenochrysene, hemifullerene, and circumtrindene) has been explored computationally within the DFT framework. To this end, both the increase in reactivity with the size of the buckybowl and complete [6,6]‐regioselectivity in the process have been analyzed in detail by using the activation strain model of reactivity in combination with the energy decomposition analysis method. These results have been compared with the parent C₆₀ fullerene, which also produces the corresponding [6,6]‐cycloadduct exclusively. The behavior of the buckybowls considered herein resembles, in general, that of C₆₀. Whereas the interaction energy between the deformed reactants along the reaction coordinate mainly controls the regioselectivity of the process, it is the interplay between the activation strain energy and the transition‐state interaction that governs the reactivity of the system.     

Efficient production of reference materials of hazardous organics using smart calibration by nuclear magnetic resonance

The accurate quantification of pesticide residues in food is an important factor in assuring the quality of life of our citizens. In general, chromatographic methods are used, which require certified reference materials (CRMs) for each analyte of interest for accurate quantitative analysis. Recently, regulation of pesticides in food, limiting the positive maximum residue (positive list system) has been brought into effect in Japan. Furthermore, ISO/IEC 17025 requires calibration and testing laboratories to program calibrations and measurements traceable to the International System of Units (SI). Accordingly, these laboratories need a suite of CRMs that are traceable to the SI. In order to address these requirements for every analyte of interest in an efficient manner, a new approach to producing SI traceable CRMs is required. Nuclear magnetic resonance (NMR) has been used widely in chemical analysis. One of the well known characteristics of NMR is the proportional relationship between peak area and the number of nuclei contributing to the peak. If accurate relative intensities of peak areas are obtained, this provides an attractive quantitative tool for organic compounds. The area of a signal from an analyte can be measured with respect to another signal originating from a comparator that has been added to the sample solution. The chosen comparator should not react with the analyte or resonate at any chemical shift similar to that of the analyte. This enables us to produce SI traceable CRMs more effectively. In this paper, we demonstrate a new approach for producing CRMs for pesticides using quantitative NMR??an SI traceable quantitative technique.     

Synthesis of functionalized α-amino-phosphine oxides and -phosphonates by addition of amines and aminoesters to 4-phosphinyl- and 4-phosphonyl-1,2-diaza-1,3-butadienes

1,2-Diaza-1,3-butadienes derived from phosphine oxides and phosphonates and with optically active substituents on N-1 and C-3 are obtained by 1,4-elimination from chlorohydrazonoalkyl-phosphine oxides and -phosphonates in the presence of bases. Michael addition (1,4-addition) of ammonia, aliphatic and aromatic amines and aminoesters to these azo-alkenes gives functionalized α-amino-phosphine oxides and -phosphonates.     

Self-trapping limited exciton diffusion in a monomeric perylene crystal as revealed by femtosecond transient absorption microscopy

Self-trapping and singlet-singlet annihilation of the free excitons in a monomeric (beta) perylene crystal were studied by using femtosecond transient absorption microscopy. The free exciton generated by the photo-excitation of the beta-perylene crystal relaxed to the self-trapped exciton with a rate constant of 7 x 10(10) s(-1). The singlet-singlet annihilation of the free exciton observed under the high excitation density conditions was competed with the self-trapping of the free exciton; we estimated the annihilation rate constant for the free exciton to be 1 x 10(-8) cm(3) s(-1) from the excitation density dependence of the free exciton decay. After self-trapping of the free exciton, no annihilation was observed in the 100 ps time range, suggesting that the diffusion coefficient was reduced drastically by self-trapping. The results show that the major factor limiting the exciton diffusion in the beta-perylene crystal is a relaxation of the free exciton to the self-trapped exciton, and not the lifetime of the exciton. Though the singlet-singlet annihilation rate constants and fluorescence lifetime of the beta-perylene crystal are similar to those of the anthracene crystal, the estimated exciton diffusion length (2 nm) in the beta-perylene crystal is much smaller than that (100 nm) in the anthracene crystal as a result of the exciton self-trapping.     

Pulsed electron nuclear double resonance studies of the photoexcited triplet state of pentacene in p-terphenyl crystals at room temperature

Pulsed electron nuclear double resonance (ENDOR) using a modified Davies-type [Phys. Lett. 47A, 1 (1974)] sequence is employed to study the hyperfine (HF) structure of the photoexcited triplet state of pentacene dispersed in protonated and deuterated p-terphenyl single crystals. The strong electron spin polarization and long phase memory time of triplet pentacene enable us to perform the ENDOR measurements on the S=1 spin system at room temperature. Proton HF tensor elements and spin density values of triplet pentacene are extracted from a detailed angular-dependent study in which the orientation of the magnetic field is varied systematically in two different pentacene planes. Analysis reveals that the pentacene molecule is no longer planar in the p-terphenyl host lattice. The distortion is more pronounced in the deuterated crystal where the unit cell dimensions are slightly smaller than those of the protonated crystal.     

Modified Markó’s aerobic oxidation of alcohols under atmospheric pressure with air or molecular oxygen at room temperature

A modified version of Markó’s aerobic oxidation procedure, using highly pure (99.995+%) CuCl with 4,7-diphenyl-1,10-phenanthroline (dpPhen), DBAD, and Cs₂CO₃ (98% purity) successfully oxidized primary and secondary alcohols to the corresponding aldehydes and ketones in excellent yield at room temperature with either air or molecular oxygen under atmospheric pressure.     

Addition of amine derivatives to phosphorylated 1,2-diaza-1,3-butadienes. Synthesis of α-aminophosphonates

Achiral and chiral 1,2-diaza-1,3-butadienes derived from phosphine oxides and phosphonates are obtained from hydrazonoalkyl-phosphine oxides and -phosphonates. Michael addition (1,4-addition) of ammonia, aminoesters and aminoalcohols to these azo-alkenes gives functionalized α-amino-phosphine oxides and -phosphonates.