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2-[4-(1,1-Dimethylethyl)phenyl]thiophene 12 was carboxylated using butyllithium and carbon dioxide to give 5-[4-(1,1-dimethylethyl)phenyl]thiophene-2-carboxylic acid 13. Conversion of the acid 13 using diphenyl phosphazidate and triethylamine gave 5-[4-(1,1-dimethylethyl)phenyl]thiophene-2-carbonyl azide 14, which was rearranged in toluene at 110 °C with loss of nitrogen to give the isocyanate 15; this in turn was treated with sodium 1-cyanoprop-1-ene 2-oxide 16 in tetrahydrofuran to give 2-cyano-N-{5-[4-(1,1-dimethylethyl)phenyl]thiophen-2-yl}-3-hydroxybut-2-enamide 17. Analogous chemistry has been utilised to synthesize both phenylheteroarylbutenamides and phenylbutenamides which display immunosuppressive activity towards proliferating concanavalin A-stimulated T-lymphocytes.

Measurements are reported on the non-linear electric field effect of the relative permittivity of aqueous systems at fields up to 107 V m–1. Over the range 273–293 K the Piekara factor (ΔIµ/E2) for water has the Langevin anticipated negative values but shows a distinct pattern with a minimum near 277 K. H2O and D2O liquids give indistinguishable values.Whilst acetone and pyridine show an essentially smooth variation of (ΔIµ/E2) over their complete concentration ranges in water, dioxan and tetrahydrofuran show similar marked variations with a distinctive positive effect near the hemihydrate compositions. The influence of temperature on the sharp positive maxima with these two solutes is reported. t-Butyl alcohol, well known to give positive (ΔIµ/E2) values in the pure liquid, does so at all concentrations above mole fraction 0.25. In many cases it is clear that the Piekara factor shows far more detail than the Iµ0 against concentration plots as the measurements are sensitive to very small changes in permittivity due to the high fields.The observations are discussed with the aim of identifying the principal factors contributing to the newly observed effects.

Dielectric dispersion and absorption curves of m-cresol solutions of poly-γ-benzyl-L-glutamate (PBLG) are measured by means of a pseudo-random noise dielectric spectrometer (PN-dielectric spectrometer) recently developed in our laboratory. This device senses the response of a sample solution to pseudo-random noise applied in the time domain. The Fourier transform of the response gives the transfer function in the frequency domain, from which the complex permittivity is obtained. In order to control the whole system and for successive calculations, a minicomputer is used. This PN-dielectric spectrometer covers 10 Hz ∼ 250 kHz and needs

Short duration, high field intensity pulses have been applied to the alcohols, butanol, propanol, ethanol and methanol. Using a frequency counter technique the non linear dielectric behaviour of these alcohols has been studied, and the results obtained compared with those of other workers. Solutions of ethanol in benzene demonstrate qualitatively the same behaviour as the higher alcohols in similar non-interacting solvents. Whilst previously the observed behaviour has been ascribed to a proton shift mechanism, an alternative is suggested involving the opening up of cyclic non-polar multimers in the electric field to form more polar species.

Conductivity, permittivity and non-linear dielectric measurements have been made for mixtures of t-butyl and benzyl alcohol with the proton acceptors, anisole, dimethylaniline and triethylamine. The results suggest that more than one mechanism may be producing the observed positive non-linear dielectric effect. Earlier work which suggests that the O—H—N hydrogen bond is stronger than the O—H—O is substantiated by the results, which suggest that the bonding between dimethyl-aniline or triethylamine and the alcohols is stronger than the intermolecular bonding between the alcohols themselves. The large increase in conductivity observed on addition of small concentrations of these amines to the alcohols is attributed to a proton transfer mechanism along chains of hydrogen bonded alcohols.

High field dielectric measurements of the “Piekara factor” have been carried out for pure water at 293 K. The measurements have been made possible by the development of a new technique capable of measuring permittivity changes ΔIµ/Iµ as low as 10–5 in samples with conductivities as high as 10–2Ω–1 m–1. Reproducible results with water having conductivities in the range 1 to 4 × 10–5Ω–1 m–1 gave ΔIµ/E2=–(1.00 ± 0.15)× 10–15 m2 V–2. The results are interpreted in terms of the low field dipole polarization factor Rp and the non-linear field effect correlation factor RS. The behaviour is that of the “classical” non-linear effect of a negative ΔIµ due to permanent dipoles.

The dynamic rotational and translational processes associated with the acetylcholine ion are of interest in view of its role as a neurochemical transmitter; the diffusion process is of particular interest as this is involved in the movement of the ion across the synaptic cleft.Proton n.m.r. measurements of diffusion and relaxation together with high resolution studies have been carried out on solutions of acetylcholine chloride in D2O. Diffusion data cover the range 20–80°C while the relaxation data cover the range –60 to +90°C. The diffusion coefficient of acetylcholine at 20°C is 12.2 × 10–10 m2 s–1 and the activation energy of the diffusion process 23 kJ mol–1. The relaxation data give activation energies of 47 kJ mol–1 and 13 kJ mol–1 below and above room temperature respectively. The 47 kJ mol–1 activation energy is thought to be due to rotation about the partial double bond between the ester oxygen and carboxyl carbon of the acetylcholine molecule. The 13 kJ mol–1 activation energy is likely to be due to rotation of the acetylcholine molecule as a whole.

High electric field pulse measurements have been made on dilute solutions of poly-γ-benzyl-L-glutamate (PBLG) in trans-1,2-dichlorethylene(I) and dioxan(II). One millisecond pulses of field amplitude up to 60 kV/cm have been used and the resulting changes in permittivity measured at 6 MHz. The measurements, which are analogous to Kerr effect birefringence work, yield values of the dipole moment and anisotropy of polarizability for PBLG. The values of the apparent dipole moment are 1930 D for (I) and 1410 D for (II), while the effective molecular anisotropy (α∥–α⊥) is 8.3 × 10–21cm3 for (I) and 10.5 × 10–21 cm3 for (II). Dispersion measurements on solution (I) led to a dipole moment of 1780 D.

Spin-lattice relaxation times in the rotating frame (T1ρ) have been measured at temperatures between –210 and 170°C for 1,2-dipalmitoyl-L-phosphatidylcholine. 1H2O. T1ρ minima corresponding to correlation frequencies of 68kHz are found, and assigned to motions of the terminal aliphatic methyl groups (–190°C), the N+(CH3)3 methyl groups (–100°C) and to low amplitude oscillatory motions of the methylene groups of the fatty acid residues (–23°C). Measurements on a per-deuterated analogue reveal a further T1ρ minimum at 61°C which is not observed in the fully protonated sample, although there is some difference of the transition temperatures. This minimum is assigned to a further 34 kHz reorientation prior to a transition from crystal to liquid crystal. Spin diffusion processes are thought to be responsible for the absence of an analogous minimum for the protonated sample. The pre-transitional minimum is revealed by the addition of 19 % water, and is assigned to a new low frequency motion of the N+(CH3)3 protons of the head group. In the lamellar liquid crystalline phase, one T1ρ is observed and may be dominated by motions of the head group protons. The absence of any change of T1ρ is the lamellar-viscous isotropic phase transition confirms that the low frequency motions of the polar head groups protons remain unchanged, in spite of a change of symmetry. A hydrophilic-continuous model of the cubic phase structure is therefore preferred. The head group conformation in both the crystalline and liquid crystalline states is such that, except for the transition region, spin diffusion occurs between the hydrophilic and hydrophobic moieties. Efficient coupling may be achieved by a gauche conformation of the phosphatidylcholine residue in the presence of water.

Measurements of the change in relative permittivity (ΔIµ) have been made as a function of applied electric field (E) at 22°C for the non-dipolar liquids n-pentane, n-hexane, n-heptane, n-octane, n-nonane, n-decane, cyclohexane, benzene, carbon tetrachloride and carbon disulphide. The measurements were made at fields of up to 2 × 107 V m–1, the ΔIµ being detected via the change in frequency of an oscillator as measured using a computing counter. The range of ΔIµ/E2 values obtained were from about 10 to 30 × 10–20m2V–2. The values were generally larger than could be attributed to the anisotropy of polarizability, particularly for the nearly spherical carbon tetrachloride molecule and much larger than the expected contributions due to electrostriction and the electrocaloric effect. The measured values are undoubtedly made up from a number of effects, including the Kielich local fluctuating intermolecular effects.

The n.m.r. parameters T1 and T1ρ, the spin-lattice relaxation times in the laboratory- and rotating-frames, respectively, have been utilized to study the molecular motions that occur in polycrystalline samples of cytosine and cytosine hydrate in the range 130–293 K. The deuterated analogues have also been studied. It is concluded that, in the monohydrate, the water molecule, but not the cytosine itself, may rotate (at a frequency of ca. 30 kHz at 200 K), the activation energy of rotation being 17.8±2.8 kJ mol–1. There is also evidence for the rotation of the amino group. Dehydration of cytosine hydrate commences around 328 K, and the enthalpy of dehydration is estimated to be 50 kJ mol–1.

A technique is described for measuring non-linear dielectric effects (NDE) in conducting media using a frequency sampling technique. The medium under investigation is contained in a dielectric cell which is part of the tuned circuit of an oscillator. The change in frequency of the oscillator on application of a square pulse of electric field is measured using a commercial computing counter. The averaging facility of the counter allows up to 104 determinations in one sequence. The measured effect is shown to be the sum of the NDE plus a Joule heating effect due to the conductance of the liquid. The true NDE is determined by extrapolation of the data to zero pulse width while the rate of change of the total effect plus a residual effect after the pulse gives information on the heating. It is shown that the heating of the liquid between the electrodes is an adiabatic process, the time of diffusion of the heat to the rest of the cell being large compared with the time of the experiment. Illustrative results are given for acetone, hexanol and dodecanol. In addition the precise measurements of the heating effect can be used for the determination of high field conductivities and thermometric, calorimetric etc. measurements in suitable cases.