Current Organic Chemistry - Volume 4, Issue 1, 2000

Cells utilize myo-inositol for osmoregulation and phosphatidylinositol signaling. Mass spectrometric and in vivo magnetic resonance spectroscopic techniques have been complementarily used in our laboratories to investigate brain myo-inositol metabolism. Mass spectrometric quantitation methods are surveyed focusing primarily on derivatization reactions, gas chromatographic separation and detection of ions. Monitoring of the m/z 373 fragment ion generated from acetate derivative provides precise quantitation of myo-inositol in biological matrices. The technique and its clinical applications are discussed. Measurement of myo-inositol transport using a stable isotope technique is illustrated for cultured neurons. In addition, the possible use of the technique in probing phosphatidylinositol turnover is discussed. An in vivo 1H magnetic resonance spectroscopic technique is described for measuring the absolute concentration of myo-inositol in human brain. Magnetic resonance spectroscopy with short echo-time enables detection of the resonance peak of myo-inositol (3.56 ppm) when the water resonance peak is suppressed by narrow band radio-frequency pulses. The review focuses on an external reference method involving collection of data from the human subject and the phantom containing aqueous myo-inositol standard solution in the same scanning session. The method takes into account differences in longitudinal and transverse relaxation time constants of myo-inositol between brain tissue and aqueous solution. Application of the technique is illustrated by measuring brain myo-inositol in Down syndrome adults and Alzheimer disease patients. Advantages and limitations of this noninvasive technique in monitoring metabolic processes are discussed.

Isotope effects on chemical shifts of intramolecularly hydrogen bonded systems are reviewed. The effects are conveniently divided into localized (intrinsic) and equilibrium isotope effects. The review covers both primary and secondary isotope effects on chemical shifts. For the localized one it is very important to distinguish between RAHB and non-RAHB types. For the RAHB systems the OH group is shown to form a stronger hydrogen bond than the OD group, whereas the opposite is true for non-RAHB. Theoretical calculations at the ab initio level (DFT) can be used to provide reliable structures, chemical shifts and isotope effects. Large intrinsic secondary isotope effects can to a good degree be related to the change in the OH(D) bond length upon deuteriation. 2ΔC(XD) isotope effects are shown to be good measures of hydrogen bond strength. So far no evidence for heavy atom movement has been convincingly advanced for RAHB systems. A number of isotope effect types have now been studied in depth, nΔC(XD), X= O, S or N, 1DN(D), 1ΔO(D), 5ΔO(D), nΔH(OD), nΔF(D). It is concluded that the possible over determination of isotope effects in hydrogen bonded systems provide a very powerful tool in studies of structure of hydrogen bonded systems. Isotope effects are studied in detail in sterically hindered systems and parameters are available to distinguish between twist of e.g. RCO groups and steric compression. Furthermore, twist of phenyl rings may also be monitored. Proton transfer reactions such as tautomerism have been studied extensively. Equilibrium isotope effects on chemical shifts have been reported in a large number of cases. The magnitude of the equilibrium isotope effects depends on the equilibrium constant. A series of parameters have been suggested as a good way to establish tautomerism in a number of difficult cases. Both deuterium and tritium primary isotope effects have now been reported in a large number of systems. Large intrinsic primary isotope effects is a good proof of double potential wells. Primary isotope effects are also studied in tautomeric systems and at different temperatures and can under such circumstances be both positive and negative.

Electron Spin Resonance (ESR) spectroscopy is the technique sine qua non for establishing the geometric and electronic structures of the free radicals participating in many organic reactions and syntheses. It also allows the mechanisms of the complex network of elementary reactions constituting the overall chemical change to be determined and the rate parameters of these reactions to be measured. Radicals can be classified into two main types - and π-radicals. -radicals, exemplified by phenyl, have their free electron orbital projecting out from a non-planar radical centre. They are usually more reactive than -radicals, exemplified by alkyl radicals in which the free electron resides in a carbon 2pz orbital perpendicular to the planar radical centre. Fluorine substitution results in a progressive change from a planer -methyl radical to a tetrahedral -trifluoromethyl radical. The regioselectivity and stereoselectivity of intermolecular and intramolecular free atom and radical additions to unsaturated systems are discussed in terms of optimal orbital overlap, steric and free valence effects as are group transfers and SH 1 and SH 2 homolytic substitution reactions. The unusual reactions of aluminium and gallium atoms with alkenes, alkynes 1,2 and 1,3 dienes and benzene are considered. Recent controversies concerning the Fenton reaction and the free radical mode of action of the new antimalarial drug Artemisinin are reviewed. The potential for applications of ESR in conjuction with spin traps in heterogeneous catalysis is outlined.

Nuclear Magnetic Resonance (NMR) spectroscopy of molecules aligned in liquid crystalline media provides information on molecular structure and order parameters. The partial alignment of the molecules in the anisotropic phase of the liquid crystals gives rise to residual intramolecular dipolar couplings which are dependent on the internuclear distances and therefore yield information on the geometry of molecules. The spectra of these aligned molecules become rapidly complex with the increase in the number of interacting spins and with decrease in the symmetry of the molecules. The spectra of these molecules are generally strongly coupled and are complex. Thus the first order analysis of the spectra as applicable to liquid state is generally not applicable and one should resort to numerical analysis using computers. In this report problems associated with the analyses of such complex spectra, methods developed to aid such analyses and the precision of the structural parameters derived are discussed. Use of mixed liquid crystals of opposite diamagnetic susceptibility anisotropies to extract information which is otherwise not possible to derive using single liquid crystals is highlighted. Current developments in the field with special emphasis on the discovery of a novel liquid crystal with low order parameter and the use of natural abundance deuterium NMR spectra of the probe molecules for the analyses of complex spectra are discussed.