Enantiomer ratio/fraction

Figure 42 Kuhn dissymmetry ratio for the series of co-polymers 112 as function of (P)- or (S)-enantiomer mole fraction.323 Reprinted with permission of the author from Fujiki, M. Polym. Prepr. (Am. Chem. Soc. Div. Polym. Chem.) 1996, 37, 454-455.

Because ee and op values are not suited for mathematical formulae, it is much simpler and clearer if enantiomer ratios are used, Up to around 1980 it was the custom, as assessed from older textbooks and reviews, to define enantiomeric and optical purity by fractions and use terms enantiomeric and optical yield for the percentage values as described earlier. 

Sublimation. Such effects can also be seen in solid-gas interphase. Scheme 30 shows the consequences of fractional sublimation of partially resolved L-mandelic acid (47). The optical purity could be enhanced or reduced, depending on the optical purity of the starting material. Since the eutectic point of mandelic acid is obtained with about a 75 25 enantiomer ratio, such a mixture is more readily sublimed than the racemate or conglomerate. Scheme 30 gives other examples of optical enrichment by sublimation. Phenyl 1-phenyl-1-propyl sulfide in 6% ee affords the sublimed compound in 74% ee, but the residue is... 

More recently, enantiomer ratios have been used as evidence of adulteration in natural foods and essential oils. If the enantiomer distribution of achiral component of a natural food does not agree with that of a questionable sample, then adulteration can be suspected. Chiral GC analysis alone may not provide adequate evidence of adulteration, so it is often used in conjunction with other instrumental methods to completely authenticate the source of a natural food. These methods include isotope ratio mass spectrometry (IRMS), which determines an overall 13C/12C ratio (Mosandl, 1995), and site-specific natural isotope fractionation measured by nuclear magnetic resonance spectroscopy (SNIF-NMR), which determines a 2H/ H ratio at different sites in a molecule (Martin et al 1993), which have largely replaced more traditional analytical methods using GC, GC-MS, and HPLC. 

Two principal metrics are used for reporting enantiomer compositions of chiral POPs the enantiomer ratio (ER) and the enantiomer fraction (EF). Most earlier studies used ER, the ratio of the (+)-enantiomer concentration over that of the (—)-enantiomer. Chromatographic parameters for calculating concentrations, such as peak area or height, can also be used. If the elution order is unknown, then the ER is reported as the ratio of the first-eluted enantiomer (El) to the second-eluted one (E2) on a specific column and conditions ... 

Hamer, T. Wiberg, K. Norstrom, R., Enantiomer fractions are preferred to enantiomer ratios for describing chiral signatures in environmental analysis Environ. Set Technol. 2000,34,218-220. 

When dealing with reactions leading to stereoisomeric products we have the additional complication that descriptors such as enantiomeric (diastereomeric) excess and enantiomeric (diastereomeric) ratio are used to describe product purities. The evaluation of RME for a specific stereoisomer, say the R enantiomer, is exactly as above using the connecting relationships for the fraction of each product shown below. 

Now, GC-IRMS can be used to measure the nitrogen isotopic composition of individual compounds [657]. Measurement of nitrogen isotope ratios was described by Merritt and Hayes [639], who modified a GC-C-IRMS system by including a reduction reactor (Cu wire) between the combustion furnace and the IRMS, for reduction of nitrogen oxides and removal of oxygen. Preston and Slater [658] have described a less complex approach which provides useful data at lower precision. Similar approaches have been described by Brand et al. [657] and Metges et al. [659]. More recently Macko et al. [660] have described a procedure, which permits GC-IRMS determination of 15N/14N ratios in nanomole quantities of amino acid enantiomers with precision of 0.3-0.4%o. A key step was optimization of the acylation step with minimal nitrogen isotope fractionation [660]. 

Just as in the case of nucleosides, the older results were re-investigated with novel methods also for tritylation of pyranosides. All the monotrityl ethers of methyl p-D-xylopyranoside and methyl oc-D-xylopyranoside have been isolated recently [311] to complement the pioneering work by Hockett and Hudson [312], The monotrityl fraction obtained [313] from methyl a-L-fucopyranoside was now found [314] to consist of 2-0- and 3-0-trityl derivatives in the ratio of 3 2 (D-enantiomer has been actually studied). 

When enantiomers are mixed together in equal concentrations, the resulting mixture is called a racemic mixture. Since the mirror image of all orientations of each molecule exist in a racemic mixture with equal probability, racemic mixtures do not rotate plane-polarized light. Unequal concentrations of enantiomers rotate plane-polarized light. In unequal concentrations, the light is rotated in the same direction as a pure sample of the excess enantiomer would rotate it but only to a fraction of the degree, the same fraction that exists as excess enantiomer. The ratio of actual... 

The quality of enantioselective reactions is numerically expressed as the so-called enantiomeric excess (ee). It is equal to the yield of the major enantiomer minus the yield of the minor enantiomer in the product whose total yield is normalized to 100%. For example, in the Sharpless epoxidation of allyl alcohol (see Figure 3.7). S - and R-glycidol are formed in a ratio of 19 1. For a total glycidol yield standardized to 100%, the S-glycidol fraction (95% yield) thus exceeds the /f-glycidol fraction (5% yield) by 90%. Consequently, S-glycidol is produced with an ee of 90%. 

Ulrich, E.M. Helsel, D.R. Eoreman, W.T., Complications with using ratios for environmental data Comparing enantiomeric ratios (ERs) and enantiomer fractions (EEs) Chemosphere 2003, 53, 531-538. 

Conglomerates and racemates can be easily distinguished from each other on the basis of their melting point phase diagrams [25]. A conglomerate system will exhibit a single eutectic minimum in its phase diagram at the mole fraction of 0.5, since at this enantiomeric ratio the system will consist of an equimolar mixture of two crystalline enantiomers that melts as if it were a pure system. Qn the other hand, a racemate system will exhibit two eutectics on either side of the mole fraction of 0.5 since both enantiomers will be foimd in the unit cells of the crystallized solid. 

To illustrate the opportunity to pre-determine different types of ring structures by the deliberate choice of substitution patterns within an cycloolefinic precursor, racemic cis-3,4-dihydroxycyclopentene 21 [96,98] was subjected to the routine reaction sequence (ozonolysis, aldolization, dephosphorylation). A bisadduct fraction was obtained in 25% for which NMR analysis showed the presence of two components in a 4 1 ratio [56]. After chromatographic separation, the main component was established to have the mixed furanoid-pyranoid structure 22 with trans-all equatorial ring junction that indeed was to be expected for the thermodynamically more favorable product derived from the (2R,3R) enantiomer of the dialdehyde. The minor product 23 arising from the (2S,3S) enantiomer, however, did not contain the presumed trans-diaxial substitution at C-3/4 of the pyranose substructure which would be forced upon by... 

At the other extreme of the absorption rate spectrum, when the absorption rate is high and portal vein concentrations are high, the presentation rates of the enantiomers to the liver exceed the maximum velocities (V ) of their metabolic pathways. This scenario results in saturation of the metabolic enzymes and large, and approximately equal, fractions of both enantiomers will pass through the liver unchanged, and the R S bioavailability ratio will approach 1 1. Given the difference in the enantiomer volumes of distribution, this will produce an R S plasma concentration ratio of approximately 2 1, just as is observed following intravenous administration. 

Brunner and Miiller (84). Various drugs have been found to bind enantio-selectively to AGP. The laevorotatory enantiomer of propranolol (Fig. 3B) is preferentially bound to AGP (42,85), the ratio of the free fractions (- +) being 0.79. This enantioselectivity is apparent over a range of AGP concentrations (85,86). Interestingly, the enantioselectivity in binding of propranolol to HSA is inverted, compared to that of AGP (42). The significant difference in the tissue distribution of the enantiomers of... 

The concentration of AGP in the plasma of healthy volunteers correlated significantly with the binding ratio (bound/free) of the enantiomers, as well as the racemic form, of methadone. The average free fractions for +)- and (—)-methadone in plasma were 0.100 and 0.142, respectively (97). Two variants of AGP, orosomucoids 2A and FI, were also found to play important determining roles in the binding of methadone enantiomers (97). The authors of the study point out that the levels of AGP variants should be considered in protein binding studies. 

For enantiomeric drugs with low organ clearance, differences in renal or hepatic clearance between stereoisomers may reflect their free fraction in the plasma and not real stereoselectivity of the ability of the organ to remove the free enantiomers (intrinsic clearance) from the plasma. Clearance differences between stereoisomers of verapamil and disopyramide may be a function of plasma protein binding differences. In addition, volumes of distribution as well as concentration ratios of stereoisomers in body fluids to total plasma and blood are influenced by plasma protein binding. For example, the larger volume of distribution and greater total body clearance of R-disopyramide compared to the S isomer may be explained by the lower... 

Enantiomeric excess or % ee (or % optical purity) = [observed specific rotation] divided by [specific rotation of pure enantiomer] X 100. Note that there are examples where the linear relationship between enantiomeric excess and optical rotation fails. A percent enantiomeric excess (% ee) of less than 100% indicates that the compound is contaminated with the other enantiomer. The ratio of enantiomers in a sample of known (measured) optical purity may be calculated as follows fraction of the major isomer = [(% ee) + 0.5 (100 - % ee)]. Thus,... 

Warfarin enantiomers are extensively metabolized by liver, possess a low hepatic extraction ratio, and are extensively bound (> 99%) to plasma proteins (Table 3). Therefore any change in the protein binding of warfarin enantiomers may alter the clearance and plasma concentrations of R- and S-warfarin [54]. Yacobi and Levy [54] studied the plasma protein binding of racemic and individual enantiomers of warfarin in human blood. The free fraction of R-warfarin was significantly (32%) larger than that of S-warfarin (Table 3). The authors concluded that the difference in the potency of warfarin enantiomers could not be solely explained by the observed differences in the protein binding of the individual enantiomers but rather by the intrinsic ability of R- and S-warfarin for interactions with extravascular receptors. 

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