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13 C hyperfine features have been detected by electron paramagnetic resonance (EPR) spectroscopy from a range of bridgehead radicals following γ-irradiation of the corresponding bromides at 77 K. For cubyl and its 4-methoxycarbonyl derivative, both parallel and perpendicular components of the 13C tensor were resolved, but only the parallel components could be detected for the 4-bromo derivative. The full 13C tensors were also obtained for bicyclo[2.2.1]heptyl and tricyclo[3.1.1.03,6]heptyl radicals, but for bicyclo[2.2.1]hexyl, bicyclo[2.2.2]octyl and bicyclo[1.1.1]pentyl radicals only the parallel components were apparent, the perpendicular regions being obscured by other signals.A linear correlation is found between A∥ and the one-bond C–H (1JC–H) coupling in the nuclear magnetic resonance (NMR) spectra of the parent bridgehead alkanes and is used in the estimation of isotropic coupling constants for the bridgehead radicals, even in those cases where A⊥ is unknown.

The EPR spectra of 7-tert-1-butyl-1-naphthylmethyl and 6-tert-butyl-2-naphthylmethyl radicals, prepared by photolysis of the hydrocarbon with tert-butyl peroxide at –40 °C, have been analysed by correlation methods: average α(C–H) coupling constants are 15.0 and 15.25 G respectively, in line with the expected relative stabilities of the two radicals and the recently reported stabilization energy for 1-naphthylmethyl.

The title radicals have been observed in the NaX zeolite using the transverse-field muon spin rotation (TF-µSR) technique and are found to be strongly associated with the zeolite surface.

Cyclohexadienyl radicals have been observed in Na-X zeolite at ambient temperature by means of the muon spin rotation technique.

Results for azoethane, 1,1′-azopropane, 2,2′-azopropane, 1,1′-azoadamantane, 2,3-diazabicyclo-[2.2.2]oct-2-ene (DBO), 1,4-dimethyl-2,3-diazabicyclo[2.2.2]oct-2-ene (Me2DBO) and cis and trans-azobenzene radical cations are presented, as formed in solid freon matrices at low temperatures. The azoalkane radical cations are all formed in σ-states, corresponding to ionisation of the ag orbital (out-of-phase lone-pair combination), while for the trans-azobenzene radical cation the assignment to the π-state cannot be definitely excluded, although experimental evidence would appear to suggest the σ-state: the cis-azobenzene radical cation isomerises to the trans-isomer. Semi-empirical calculations were also performed on selected examples of the above species, the conclusions from which are discussed.

Following the adsorption of (Z)- or (E)-piperylene (penta-1,3-diene), penta-1,4-diene or hexa-1,5-diene onto H-mordenite, EPR signals characteristic of 9-octalin radical cations 1/6 were recorded. Comparative studies of these dienes were made in solid freon matrices which indicate that a dominant mechanism involving Bronsted acid catalysis is required to explain the main molecular transformations, prior to radical cation formation.

A series of sulfamides has been synthesised and their primary radical cations studied by EPR spectroscopy following γ-radiolysis in low-temperature freon matrices. These species are readily bleached by visible light (>570 nm), to give secondary radicals, the nature of which varies with the sulfamide used. The 14N hyperfine data show that the SOMO comprises both nitrogen centres and furthermore that the 14N tensors are parallel. This implies that a distortion of the sulfamide system occurs on ionisation, since the neutral species (at least for sulfamide and its tetramethyl derivative) adopt bisected structures with an appreciable angle between the nitrogen 2p orbitals. MO calculations indicate that the obvious possibility of a twisting of the N-centres through 90° to form regular ‘allylic ’structures is disfavoured energetically over the retention of the basic bisected geometry, and we suggest therefore that it is a ‘bent-bonding ’distortion that operates to render the N-orbital axes parallel, in accord with the EPR data. Additionally, we have studied radicals formed by radiolysis of the pure sulfamides at 77 K, and conclude that much of the radiation chemistry in these pure systems is driven by electron capture events: these are not possible in the freon media which are themselves efficient electron capture materials, and thus remove them from the reaction system.

EPR spectroscopy shows that the radical cation of cyclooctatetraene (1), as formed by γ-radiolysis in solid freon matrices at 77 K, is converted by visible (blue) light (400–600 nm) to the isomeric bicyclo[3.3.0]octa-2,6-diene-4,8-diyl isomer (2). On subsequently irradiating with red light (>570 nm), 2 is converted to a third isomer with couplings (a= 13.5 G) to two protons which are α- to the SOMO, as may be judged from the g and A anisotropy. Restricted HF AM1 calculations establish the structure 11 for this isomer and provide a rationale for the conversion of 2 to 11 in the clear correlation that is found between the two highest occupied orbitals of excited 2* and 11. Other local minima are located by extensive exploration of the C8H8+˙ potential energy surface, and possible conversions between selected examples of these are calculated to compare with published experimental results.

EPR spectroscopy has been used to study radical cations derived from organosilicon and organotin compounds, as isolated in solid trichlorofluoromethane matrices at low temperatures. For the organotin radical cations depletion of electron density occurs from a unique C–Sn bond, and leads to dissociation on annealing for allyl- and benzyl-tin species, yielding allyl and benzyl radicals, respectively: remarkably, the dissociation is reversible for p-MeOC6H4CH2SnBu3˙+ radical cations. No such fragmentation is observed for the corresponding organosilicon species, even on annealing to the melting point of the matrix (ca. 160 K) despite evidence that the C–Si bonds are similarly depleted on ionisation. The Me2N(CH2)3SnBu3˙+ radical cation is unstable at 77 K, and fragments to form butyl radicals as the only detectable paramagnetic species.

Following γ-radiolysis of dilute solutions of imines in trichlorofluoromethane at 77 K, EPR spectra of the corresponding radical cations were recorded. For PhCHNEt and PhCHNCHMe2 the primary 2A′ cations were formed, but in each case as a mixture of cations with different conformations of the alkyl group. The complex spectra were assigned with the aid of those for the deuteriated analogues PhCDNEt and PhCDNCHMe2. For Ph2CNEt, two cations differing by the confomation of the ethyl group were observed; for Ph2CNCHMe2, only a single conformer was evident. In an attempt to induce a σ/π‘crossover’, the compounds p-Cl–C6H4CHNBut and p-MeO–C6H4CHNBut were studied: the latter did indeed form a π-cation, while the former gave the normal 2A′ cation. The neopentyl derivatives PhCHNCH2But and Ph2CNCH2But gave only the distonic radical cations PhCH[graphic omitted]H–CH2C(Me2)CH2˙ and Ph2C[graphic omitted]H–CH2C(Me2)CH2˙, formed by an intramolecular hydrogen atom transfer. By studying the series of deuteriated compounds, PhCDNCH2CH2CH2CH3, PhCDNCD2CH2CH2CH3 and PhCHNCD2CH2CH2CH3, it is shown that, on radiolytically-induced single electron oxidation, PhCHNBu gives the distonic radical cation PhCH[graphic omitted]HCH2CH2ĊHCH3.

Addition of muonium takes place at the terminus of the conjugated diacetylene unit in MeCC–CCMe to give MeC(Mu)Ċ–CCMe radicals, but to the adjacent position in Me3SiCC–CCSiMe3 to give Me3SiĊC(Mu)–CCSiMe3 radicals.

Muon avoided level crossing spectroscopy (ALC) shows that in muonium atom addition to fulvenes, radicals are formed exclusively by addition to the 1 and 2 positions.

Radical cations of dibenzylmercury and its p-X derivatives (X = Me, MeS, MeO, Cl) and of diphenylmercury and its p-X derivatives (X = Cl, Et, Me, MeO) have been generated by γ-radiolysis of dilute solutions of the parent compounds in CFCl3 matrices at 77 K. The EPR results for the dibenzylmercury series show all members to be σu-radical cations with singly occupied molecular orbitals approximating to the form (I). The parallel and perpendicular |+½> components of the 199Hg spectrum are almost coincident, giving an intense low-field isotropic line: this shows a substructure typical of an anisotropic doublet coupling, and arises from a single solvent fluorine atom, but is unprecedentedly large for radical-cation superhyperfine couplings in freon matrices. These additional couplings were absent when the experiments were repeated using a CCl4 matrix which confirms the 19F assignment.The diphenylmercury radical cation is also of the σu-type, along with its dimethyl and diethyl derivatives, although the spin density on mercury is reduced to ca. 50% of that in the dibenzyl series. In contrast, the dimethoxy and dichloro derivatives are formed in π-states with apparently negligible spin density on the mercury atom. Thus the σu- and π-levels must be very close in energy, so that an electronic crossover can be induced by appropriate substitution.MNDO calculations were also performed on these radicals. While there is an overall accord with the experimental results, there are important differences: for instance, F-σ* complexes are not predicted to be stable ‘gas-phase’ energy minima. However, constraints placed on the geometry such that the R2Hg˙+ radical cation must be within ca. 2–4 Ă of a CFCl3 molecule, as would be the case in the solid matrix, can be modelled, and under these conditions appreciable 19F couplings are predicted.

Following adsorption of cyclopentene onto H-mordenite at low temperatures an EPR spectrum was recorded at 77 K which can be unequivocally assigned to the radical cation of 1,2,3,4,5,6,7,8-octahydronaphthalene (9-octalin), since it is identical with the spectrum recorded from an authentic sample of 9-octalin following γ-irradiation in a CFCl3 matrix. This radical shows an interesting dynamic behaviour in terms of a concerted inversion of both rings that modulates the pseudoaxial and pseudoequatorial coupling. On initial adsorption at 195 K the activation energy associated with this process is 14.4 kJ mol–1(actually less than that measured in solution by ODMR) but which surprisingly increases to 28.3 kJ mol–1 on warming the sample to 295 K. This is interpreted in terms of radicals located at differing adsorption sites.A similar adsorption study of dimethylacetylene on this zeolite led, at 150 K, to the detection of a spectrum with an odd number of broadish lines and a spacing of ca. 10 G which we attribute to the formation of the tetramethylcyclobutadiene radical cation. On heating to 350 K, the spectrum of the hexamethylbenzene radical cation was observed.A comparative study of these compounds in freon matrices at varying concentrations was also made in order to probe the chemical properties of their radical cations by an authentic and independent method.

Following adsorption of cyclopentene onto H-mordenite, the ESR spectrum of the ‘dimeric’ 1,2,3,4,5,6,7,8-octahydronaphthalene radical cation was observed.

Exposure of 1-methylimidazole to spin-polarised positive muons leads to the radical VI in contrast with the alternative structure I that was observed following X-irradiation of a single crystal of imidazole. [graphic omitted]

ESR spectroscopy shows that the radical cation of trans-azobenzene exists as the (n–)σ-state, with negligible delocalisation of spin density onto the phenyl groups.

Following γ-irradiation of cyclo-octatetraene in Freon solvents at 77 K, a single central feature was observed by ESR spectroscopy, from the parent radical cation; after bleaching with visible light, this changed to a triplet (36.4 G) of quintets (7.8 G) pattern, assigned to the rearranged cation (IV).

A series of imine radical cations has been studied by EPR spectroscopy, generated in low-temperature halogenocarbon matrices by γ-radiolysis. Radicals of the type ArCHNR˙+[Ar = Ph or p-Me-C6H–4] tend to be formed in the 2A′ state, corresponding to ionisation of the in-plane (mainly the nitrogen lone-pair) a′ orbital (I). These are isostructural with the corresponding vinyl radicals and show angular geometries at the radical centres and large couplings (ca. 85 G) to the proton trans to the nominally nitrogen-localised SOMO (I). When R = But, a 12 G long-range coupling is observed to a single proton from the But group, arising via the W-configuration (II). This coupling was found to persist in the CFCl3 matrix up to its melting point (ca. 160 K), but was lost reversibly in the higher melting CCl4 matrix at ca. 200 K.When R = phenyl, the radical centre is rendered linear, because of the partial π-bonding between the aromatic ring and the nitrogen atom due to delocalisation of the unpaired electron, as shown by a fall in the parallel (14N) coupling with a concomitant increase in the nitrogen 2p/2s ratio, and by the observation of couplings to the ortho and para phenyl protons.For imines derived from benzophenone (Ph2CNR) the tendency is for ionisation to occur from the π-orbital (III) which has large spin densities on the para carbon atoms.Benzophenone imine (Ph2CNH), in addition to forming the π-state (III), was found to deprotonate, giving rise to the Ph2CN˙ radical. Similar behaviour was shown by benzophenone oxime, which gave only the corresponding iminoxyl radical (Ph2CN—O˙), and we propose that this is due to the dissolution of the latter two materials in the form of hydrogen-bonded molecular clusters in the non-polar freon solvent, thus facilitating deprotonation of the primary cations.

Implantation of positive muons into samples of PhCCPh and PhCCMe at 298 K led to the formation of the radicals PhĊC(Mu)Ph and PhĊC(Mu)Me; in the case of the latter compound, the alternative MeĊC(Mu)Ph radical was not detected. Additionally, cyclohexadienyl radicals formed by muonium atom addition to the aromatic rings were observed, in lower yield, allowing spin-delocalisation parameters (Δx) to be determined for the –CCR substituents. During irradiation of Me3SiCCMe, the Me3SiĊC(Mu)Me radical was observed.

ESR spectroscopy shows that the SOMO in 1-alkylimidazole radical cations corresponds to the π3 orbital, as is the case for pyrrole, furan, and thiophene cations, but there is a nodal shift in the wavefunction which distributes most of the spin density unsymmetrically between the two nitrogen atoms.

The aim of this work has been to study various muonium containing radicals not previously studied by the μSR technique with a view to determining the effect of a bound muonium atom on the radical structures as compared with their hydrogen analogues. In the first group, muonium addition to the aromatic rings of styrene, phenylacetylene and allylbenzene are compared with the more important addition to the substituent double or triple bonds. In the second group, β-muonium substituted cyclopentyl and cycloheptyl radicals are compared with their protiated versions. In the third group, radicals obtained following muonium addition to trimethylsilylethene, tri (methoxysilyl)-ethene, and 1-chloro-2, 2-dimethylethene are discussed with respect to the competition between the β-muonium atom, and β-silicon or β-chlorine substituents for control of the conformation of the radical.

A good linear correlation exists between the 29Si coupling constant of a silicon-centred radical and J(29SiH) for the corresponding silane. Deviations from this line for chlorine and silicon substituents are interpreted in terms of delocalization in the radicals.

ESR data for the bis(trimethylsilyl)silyl radical are reported. Comparison of the hyperfine coupling constants of this radical with those for other silyl radicals indicates that the configuration is more pyramidal than expected.

Following γ-irradiation of dilute solutions of dibenzylmercury and di(p-t-butylbenzyl)mercury in Freon solvents at 77 K, 199Hg and 201Hg features were observed in their ESR spectra which are consistent with the formation of the parent radical cations, upon annealing at 150 K, unimolecular fragmentation occurs, with formation of benzyl radicals.

On the basis of the muon hyperfine coupling constants, it is concluded that the pairs of substituents in cyclohexadienyl radicals operate on the spin-density distribution in a “capto-dative” manner, as they do in benzyl radicals, when direct conjugation with the radical centre is possible; however, for other arrangements of the substituents, opposing effects are found.

ESR spectroscopy shows that for the radical cations of phenylsilanes, PhSiR3+·, the unpaired electron occupies the ψA (a2) orbital when R3 Cl3, PhCl2, MeCl2 or Ph2Cl, but occupies the ψs orbital (b1 when R3  PhHCl.

A representative series is studies of organic radicals formed by the effective addition of muonium to the carbonyl oxygen atom of aldehydes, ketones, esters and amides. Low values of the muonelectron hyperfine coupling are measured which are particularly sensitive to radical structure and dynamics. The systematics of these values are discussed in terms of the opposing contributions of conjugation and hyperconjugation.

Based on analysis of ESR spectra, it is suggested that the initial species formed by electron loss from oxirane ( 13 C) in CFCl 3 at 77 K is the ring-closed o( n ) radical, rather than the ring-opened “allylic” radical.

The radical cations of the trimethylsilyl esters of acetic and trifluoroacetic acids have been observed by ESR spectroscopy following the γ-irradiation of dilute frozen solutions of the respective esters in CFCl3 at 77 K. The results show that the unpaired electron is largely confined to the Me3Si group in both cations. On annealing to the matrix softening point, intramolecular proton transfer occurs, to give the rearranged cations RC(= O + H)OSiMe2CAH2.

Glucose-stimulated (pro)insulin biosynthesis is markedly inhibited is mouse pancreatic islets incubated with micromolar concentrations of 2-5A ‘core’, (A2'p5'A2'p5'A). Total protein synthesis was also reduced, but to a lesser extent, while insulin release and total insulin content of the islets was untouched by 2-5A ‘core’. Evidence is given for the presence of a 2-5A-dependent endoribonuclease which mediates these effects.

The effects of glucose on insulin biosynthesis were studied by measuring the incorporation of radiolabelled amino acids into proinsulin/insulin in isolated rat islets. The islets were pulse labelled for 15 min with [3H]leucine (present in rat insulin I and II) or [35S]methionine (unique to rat insulin II) and then incubated for a 165 min post-label (chase) period during which the majority of labelled proinsulin was converted to insulin but under conditions whereby greater than 95% of radiolabelled proinsulin or insulin was retained in the islets. The newly synthesized, labelled, insulin was analyzed by high performance liquid chromatography. Rat I and II insulin biosynthesis was stimulated by 16.7 mM glucose to the same extent.

SummaryThe lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these LHA LepRb neurons innervate the VTA, and leptin action on these neurons restores VTA expression of the rate-limiting enzyme in DA production along with mesolimbic DA content in leptin-deficient animals. Thus, these findings reveal that LHA LepRb neurons link anorexic leptin action to the mesolimbic DA system.

The activation energy for cis⇌trans isomerisation of the 1-(2-pyridyl)ethyl radical has been measured by the muon spin rotation technique.

Exposure of 1,1-dimethylallene to a beam of spin-polarised, positive muons resulted in the effective addition of muonium atoms to the central carbon atom, giving the muonated 1,1-dimethylallyl radical, Me 2 CCMu-⋯H 2 , and to the methylene carbon atom, giving the vinyl radical, Me 2 C⋯CH 2 Mu. The muon—electron hyperfine coupling constants in these radicals, and their temperature dependences, are compared with ESR data for related protic radicals.

The radical cation, Ph2PCH2PPh2+˙ has a SOMO which is localised on one phosphorus centre; however, one form of the Ph2PCH2CH2PPh2+˙ cation has two equivalent phosphorus nuclei, the unusual form of the e.s.r. spectrum suggesting that the directions of the s–p hybrid orbitals on each phosphorus atom subtend an angle of about 90°.

The anisotropic 14N couplings (2B) in silyl-aminium radical cations indicate appreciable delocation of spin-density onto the silicon substituents.

The pancreatic B cell has been used as a model to compare the release of newly synthesized prohormone/hormone with that of stored hormone. Secretion of newly synthesized proinsulin/insulin (labeled with [3H]leucine during a 5-min pulse) and stored total immunoreactive insulin was monitored from isolated rat pancreatic islets at basal and stimulatory glucose concentrations over 180 min. By 180 min, 15% of the islet content of stored insulin was released at 16.7 mM glucose compared with 2% at 2.8 mM glucose. After a 30-min lag period, release of newly synthesized (labeled) proinsulin and insulin was detected; from 60 min onwards this release was stimulated up to 11-fold by 16.7 mM glucose. At 180 min, 60% of the initial islet content of labeled proinsulin was released at 16.7 mM glucose and 6% at 2.8 mM glucose. Specific radioactivity of the released newly synthesized hormone relative to that of material in islets indicated its preferential release. A similar degree of isotopic enrichment of released, labeled products was observed at both glucose concentrations. Quantitative HPLC analysis of labeled products indicated that glucose had no effect on intracellular proinsulin to insulin conversion; release of both newly synthesized proinsulin and insulin was sensitive to glucose stimulation; 90% of the newly synthesized hormone was released as insulin; and only 0.5% of proinsulin was rapidly released (between 30 and 60 min) in a glucose-independent fashion. It is thus concluded that the major portion of released hormone, whether old or new, processed or unprocessed, is directed through the regulated pathway, and therefore the small (less than 1%) amount released via a constitutive pathway cannot explain the preferential release of newly formed products from the B cell.

Islets of Langerhans isolated from adult rats were maintained in tissue culture for 3 days in the continued presence of [3H]leucine. Labelled proinsulin, C-peptide and insulin were measured by quantitative h.p.l.c., a method which also allowed for resolution of C-peptide I and II, and of insulin I and II (the products of the two rat insulin genes). The results showed that: (1) at early times, proinsulin was the major radiolabelled product; with progressive time in culture, intra-islet levels of [3H]proinsulin decreased, despite continuous labelling with [3H]leucine, indicating that the combined rates of proinsulin conversion into insulin and of proinsulin release, exceeded the rate of synthesis; (2) insulin I levels were always greater than those of insulin II, both in the islets and for products released to the medium; (3) the molar ratio of [3H]insulin I and II to their respective 3H-labelled C-peptides increased with time for products retained within islets, reaching a value close to 3:1 by 3 days; by contrast, for products released to the medium during the culture period, the ratio was always close to unity; (4) when islets were incubated with [3H]leucine for 2 days, and then left for a further 1 day without label (chase period), the intra-islet [3H]insulin/[3H]C-peptide ratios rose to values as high as 9:1. Again, for material released to the medium, the values were close to 1:1; (5) it is concluded that C-peptide is degraded more rapidly than insulin within islet cells, thereby accounting for the elevated insulin/C-peptide ratios. The difference between the ratios observed in the islets and those for material released to the medium is taken to indicate that degradation occurs in a discrete cellular compartment and not in the secretory granule itself.

Isolated rat pancreatic islets were pulse-labeled for 5 min with [3H]leucine then chased for 25 min, during which time endogenously labeled [3H]proinsulin becomes predominantly compartmented in immature secretory granules. The islets were then homogenized in isotonic sucrose (pH 7.4) and a beta-granule preparation obtained by differential centrifugation and discontinuous sucrose gradient ultracentrifugation. This preparation was enriched 8-fold in beta-granules. Aside from contamination with mitochondria and a limited number of lysosomes, the beta-granule preparation was essentially free of any other organelles involved in proinsulin synthesis and packaging (i.e. microsomal elements and, more particularly, Golgi complex). Conversion of endogenously labeled [3H]proinsulin was followed in this beta-granule fraction for up to 2 h at 37 degrees C in a buffer (pH 7.3) that mimicked the cationic constituents of B-cell cytosol, during which time 92% of the beta-granules remained intact. Proinsulin conversion was analyzed by high performance liquid chromatography. The rate of proinsulin conversion to insulin was stimulated by 2.2 +/- 0.1-fold (n = 6) (at a 60-min incubation) in the presence of ATP (2 mM) and an ATP regenerating system compared to beta-granule preparations incubated without ATP. This ATP stimulation was abolished in the presence of beta-granule proton pump ATPase inhibitors (tributyltin, 2.5 microM, or 1,3-dicyclohexylcarbodiimide, 50 microM). Inhibitors of mitochondrial proton pump ATPases (sodium azide, 20 mM, or oligomycin, 10 micrograms/ml) had no effect on the ATP stimulation of proinsulin conversion. When granules were incubated in a more acidic buffer (pH 5.5), proinsulin conversion was increased relative to that at pH 7.3. At pH 5.5, ATP no longer stimulated conversion, and tributyltin and 1,3-dicyclohexylcarbodiimide had no effect. Disrupted granules only converted proinsulin to a limited extent, and neither ATP nor the inhibitors affected conversion. It is therefore suggested that ATP stimulation of proinsulin conversion in isolated, intact, beta-granules is secondary to intragranular acidification by an ATP-dependent proton pump (reflecting the low pH optimum for proinsulin conversion), rather than ATP dependence of converting activity per se.

Recent advances in molecular and cell biology may allow for the development of novel strategies for the treatment and cure of type 1 diabetes. In particular, it is now possible to envisage restoration of insulin secretion by gene or cell-replacement therapy. The β-cell is, however, remarkably sophisticated, and many of the features of this highly differentiated secretory cell will have to be faithfully mimicked in surrogate cells. In particular, insulin is normally secreted in a well-regulated fashion in rapid response to the metabolic needs of the individual and most specifically (but not exclusively) to changes in circulating levels of glucose. Such regulated secretion will be indispensable in order to avoid both hyper- and hypoglycemic episodes and depends on the ability of cells to store insulin in secretory granules before exocytosis in response to physiological stimuli. Furthermore, any newly created insulin-secreting cell will have to be able to adapt to alterations in insulin requirements that accompany changes with exercise, body weight, and aging. Fine tuning of insulin secretion over the longer term will also be important to avoid “clinical shifting” that could be caused by over-insulinization, including increased adiposity and cardiovascular disease. Finally, it will be necessary to ensure that newly created or implanted (surrogate) β-cells are protected in some way from recognition by the immune system and in particular from autoimmune destruction.

Sulphur centred radicals of the type R2C(Mu)–S˙ have been observed by the µSR technique, during the irradiation of a number of thiocarbonyl compounds with positive muons; such thiyl radicals, RS˙, have never been detected by e.s.r. spectroscopy in the liquid phase.

A linear correlation is found between CA π-bond energies in compounds of the type H2CARn(or HCARn–1) and β-proton hyperfine coupling constants for the corresponding radicals H3C–ȦRn(or H2CARn-1): an empirical method is therefore available for either estimating π-bond energies from e.s.r. data or predicting hyperfine coupling constants from bond energy data.