Aqueous shift reagents

M.S. Albert, W. Huang, J.H. Lee, J.A. Balschi and C.S. Springer, Aqueous shift reagents for high-resolution cation NMR, VI, Titration curves for in vivo 23Na and HiO MRS obtained from rat blood, NMR Biomed. 6 (1993) 7. 

The aquo-complexes of the lanthanides are often used as aqueous shift reagents. Their application, however, is restricted to the acidic side of neutral pH due to the precipitation of hydroxides at higher pH values. The use of the R(EDTA) chelates at higher pH has been suggested and a characterization study has been carried out in this laboratory, (Elgavish and Reuben, 1976). With carboxylates as substrates the useful pH range is between 6 and 10, confined on the acidic side by the formation of carboxylic acid and on the basic side by the formation of hydroxo complexes of the chelates. The reagent-substrate stoichiometry is practically 1 1. 

Most biochemically relevant high-spin systems have such short 7j-relaxation times that their EPR is broadened beyond detection at ambient temperatures. An exception is the class of S = 5/2 Mn" systems with D hx. Also, S = 7/2 Gd"1-based MRI shift reagents exhibit readily detectable room-temperature EPR spectra. Otherwise, aqueous-solution transition ion bioEPR is limited to complexes of S = 1/2 metals, in particular Cu", and to a lesser extent VIV02+, NiIn, Ni1, Mov, and Wv. Cupric is the stable oxidation state of biological copper under aerobic conditions, however, the other metals are stable as Vv, Ni", MoVI, and WVI, and, therefore, the other oxidation states associated with S = 1/2 paramagnetism may exhibit oxidative or reductive reactivity and may thus require specific experimental precautions such as strict anaerobicity over the course of the EPR experiment. 

Granot and Reuben report an example of an aqueous chiral shift reagent. In water, several proton resonances of norepinephrine exhibit nonequivalence in the presence of cobaltous adenosine-5 -triphosphate (101). 

The determination of ee with chiral lanthanide shift reagents is normally performed in organic solvents. However, the development of chiral reagents capable of inducing shift nonequivalence in water, which is the appropriate solvent for many natural products, is of great importance. The europium(III) (R)-propylenediaminetetraacetate ion (Table 1) has been proposed as a chiral reagent suitable for use in aqueous solution90. 

Cation flux rates were assessed for 10 directly in phospholipid vesicles using a dynamic 23Na NMR method. In this procedure, addition of a Dy3+ shift reagent to an aqueous vesicle solution prepared in the presence of Na+ results in an external Na+ signal shifted with respect to internal Na+. With the incorporation of a channel former, the line width broadens, reflecting dynamic exchange between internal and external Na+ through the membrane channel. Consequently, the linewidth varies directly with cation flux and a plot of [channel] versus linewidth permits determi-... 

Although quite new on the scientific scene, the lanthanide complexes of the texaphyrins are considered to be of particular interest. This derives in larger measure from their documented stability in aqueous solution and the relative ease with which the basic core structure can be subjected to variations in substituents and functionality. With the increasing use of lanthanide-based shift reagents in medical diagnosis, the continued study of these new systems could prove to be of considerable interest... 

Lanthanide chlorides (473) and nitrates (474,475) have been used as aqueous LSR for investigating the structures of a number of carbohydrates. Shifts induced by Ln " ions in the proton spectrum of methoxyacetate have been discussed. (476) The water-soluble Eu complexes of pyridoxalideneaspartic acid and o-vanillideneaspartic acid have been suggested as suitable shift reagents. They have been tested with aqueous solutions of amino-acids and peptides. (477)... 

The complex formed by extraction of uranium(IV) from an acidic aqueous solution by benzoyltrifluoroacetone in carbon tetrachloride is also reported to be a useful shift reagent, the shifts induced being to lower frequency. (4) Adducts with complexes formed from uranium(IV) and other fluorinated diketones are also mentioned, but no details of shifts are given. 

In the nineteen-eighties stoichiometric amounts of conventional Lewis acids such as TiCl4, AICI3, SnCU, BFs-Olt,., Mgl r, and ZnCU were frequently used for HDA reactions of siloxy-substituted dienes with heterodienophiles [286, 287]. Danishefsky et al., however, found that a lanthanide shift reagent such as Eu(fod)3 can promote the cycloaddition catalytically [294]. Several Bronsted and Lewis acids have recently been shown to have high catalytic activity in the DA reaction of siloxy-substituted dienes in non-aqueous or aqueous media, and elaboration of Lewis acids has achieved unique chemo- and regioselectivity. 

Intractable n.m.r. spectra can sometimes be resolved by the addition of paramagnetic ions if the compound forms a complex with the ions. Eu and Pr " are particularly usefUl they shift the signals in opposite directions. The method can be us in aqueous solution, where shift reagents are not applicable. With the wide availability of high-field n.m.r. instruments, this method has become less useful than it was some ten years ago but, if two... 

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