1H and 2H NMR studies of benzene confined in porous solids: melting point depression and pore size distribution.

The pore size distributions of four controlled pore glasses and three silica gels with nominal diameters in the range 4-24 nm were determined by measuring the 1H and 2H NMR signals from the non-frozen fraction of confined benzene and perdeuterated benzene as a function of temperature, in steps of ca. 0.1-1 K. The liquid and solid components of the adsorbate were distinguished, on the basis of the spin-spin relaxation time T2, by employing a spin-echo sequence. The experimental intensity curves of the liquid component are well represented by a sum of two error functions. The mean melting point depression of benzene and perdeuterated benzene confined in the four controlled pore glasses, with pore radius R, follows the simplified Gibbs-Thompson equation DeltaT=kp/R with a kp value of 44 K nm. As expected, the kp value mainly determines the position of the pore size distribution curve, i.e., the mean pore radius, while the transition width determines the shape of the pore size distribution curve. The excellent agreement between the results from the 1H and 2H measurements shows that the effect of the background absorption from protons in physisorbed water and silanol groups is negligible under the experimental conditions used. The overall pore size distributions determined by NMR are in reasonable agreement with the results specified by the manufacturer, or measured by us using the N2 sorption technique. The NMR method, which is complementary to the conventional gas sorption method, is particularly appropriate for studying pore sizes in the mesoporous range.

Diffusion processes in confined materials.

The diffusion coefficient for cyclohexane confined within pores of diameter 40 to 500 A has been measured as a function of temperature between 296 and 180 K, and is compared to values obtained for the bulk material. A substantial liquid-like signal is observed in the region of the depressed freezing points and a diffusion coefficient is measurable in all samples to well below these temperatures. The diffusion data appear to be continuous over the freezing region. These observations suggest persisting molten layers at interfaces which exchange with crystals forming within the silica pores. The diffusion coefficient of the molecules in the surface layer is three orders of magnitude larger than in the plastic phase of bulk cyclohexane.

Nuclear magnetic resonance studies of thyrotropin-releasing hormone (TRH) and analogues incorporating D-histidine and 4-hydroxy-L-proline.

NMR studies have been used to examine conformational effects in thyrotropin-releasing hormone (TRH), the epimer incorporating D-His, and their analogues where trans- and cis-4-hydroxy-L-proline replace L-proline (Pro). In all six compounds the observed overall conformation of the major conformer around the Pro-His amide bond, and the observed increase of the cis/trans ratio between the conformers when L-His is replaced by D-His, can be accommodated by assuming that a ten-membered ring is formed by hydrogen bonding between the N-H of the Pro carboxamide function and the N pi-atom of the His imidazole nucleus.

Synthesis of a new kainic acid based selective ligand as a potential photoaffinity label of non-NMDA excitatory amino acid receptors in chicken brain.

The synthesis of two analogues of kainic acid (KA) incorporating photo-activatible moieties attached either on the gamma-carboxy function (gamma-amide 1) or the isopropenyl side-chain (amide 2) is described. The synthesis of the former amide involves coupling of N-(tert-butoxycarbonyl)-protected alpha-diphenylmethyl kainate with 2-(4-azidobenzamido)ethylamine (5) followed by trifluoroacetic acid mediated complete deprotection. Amide 2 was synthesized by palladium-mediated allylic amination, with 4,4'-dimethoxybenzhydrylamine (DMBA), of N-(9-fluorenylmethoxycarbonyl)-protected dimethyl kainate, followed by splitting the DMB-group with formic acid, coupling with N-hydroxysuccinimidoyl 4-azidobenzoate and finally complete deprotection by saponification. Preliminary pharmacological studies in chicken brain membranes showed that amide 2 is a stronger inhibitor of [3H]KA binding on chicken cerebellar membranes than is amide 1 and that amide 2 has specificity only for the cerebellar, as opposed to the telencephalon, type of non-NMDA binding sites.

Solid-phase synthesis and spectroscopic studies of TRH analogues incorporating cis- and trans-4-hydroxy-L-proline.

An efficient solid-phase synthesis of the TRH analogue Glp-His(Nim-Trt)-Hyp-OH is described. Na-Fmoc protected amino acids and DCC/HOBt activation were employed. The bulky and mild-acid-sensitive 2-chlorotrityl resin, utilised as the solid support, completely suppressed dioxopiperazine formation. The tripeptide is a key intermediate in the synthesis of TRH analogues incorporating cis- and trans-4-hydroxy-L-proline. The tripeptide was converted, with inversion of configuration at C-4 of the Hyp residue, to Glp-His(Nim-Trt)-cHyp lactone in the presence of triphenylphosphine-diethyl azodicarboxylate (TPP-DEAD). One-pot MeOH-TPP-DEAD transesterification of the lactone, followed by Nim-detritylation, provided Glp-His-cHyp-OMe. This ester gave the corresponding amide and acid on ammonolysis and saponification, respectively. A high-field 1H NMR investigation of Glp-His-cHyp-OH and its diastereomer Glp-His-Hyp-OH, obtained by Nim-detritylation of the key tripeptide, showed that the configuration at C-4 of the prolyl residues is critical for the determination of the preferred three-dimensional structure of the molecules.

Cyanidin 3-[6-(p-coumaroyl)-2-(xylosyl)-glucoside]-5-glucoside and other anthocyanins from fruits of Sambucus canadensis.

From the fruits of Sambucus canadensis four anthocyanin glycosides have been isolated by successive application of an ion-exchange resin, droplet-counter chromatography and gel filtration. The structure of the novel, major (69.8%) pigment, cyanidin 3-O-[6-O-(E-p-coumaroyl-2-O-(beta-D-xylopyranosyl)-beta-D- glucopyranoside]-5-O-beta-D-glucopyranoside, was determined by means of chemical degradation, chromatography and spectroscopy, especially homo- and heteronuclear two-dimensional NMR techniques. The other anthocyanins were identified as cyanidin 3-sambubioside-5-glucoside (22.7%), cyanidin 3-sambubioside (2.3%) and cyanidin 3-glucoside (2.1%).

Natural abundance carbon-13 and deuterium NMR studies on the liquid and solid phases of tert-butyl iodide.

Carbon-13, deuterium and proton NMR line shapes of polycrystalline tert-butyl iodide (1) have been studied between 200 K and the melting point (239 K). Carbon-13 and deuterium spin-lattice relaxation times (T1 ) were measured between 313 and 200 K in the liquid and solid phases of 1. The NMR line shape data indicate the occurrence of two disordered phases of 1 between the melting point and 222 K. An analysis of the 13 C and 2 H T1 relaxation times is reported. The 13 C and 2 H T1 relaxation is governed by overall molecular tumbling in the liquid and disordered phases of 1, whereas the 13 C T1 relaxation in the ordered solid is governed by uniaxial molecular reorientation of the tert-butyl group. Rotational correlation times, activation energies and pre-exponential factors were obtained from the T1 data by using the Arrhenius equation. Significantly different activation parameters were obtained for the two disordered solids. The effective correlation time at the melting point of 1 (ca. 5 ps) is 2-3 times longer than for other globular tert-butyl compounds.