Enantiomers difference

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

Discrimination between the enantiomers of a racemic mixture is a complex task in analytical sciences. Because enantiomers differ only in their structural orientation, and not in their physico-chemical properties, separation can only be achieved within an environment which is unichiral. Unichiral means that a counterpart of the race-mate to be separated consists of a pure enantiomeric form, or shows at least enrichment in one isomeric form. Discrimination or separation can be performed by a wide variety of adsorption techniques, e.g. chromatography in different modes and electrophoresis. As explained above, the enantioseparation of a racemate requires a non-racemic counterpart, and this can be presented in three different ways ... 

On the other hand, because enantiomers differ in their three-dimensional structure, they often interact with biochemical molecules in different ways. As a result, they may show quite different physiological properties. Consider, for example, amphetamine, often used illicitly as an upper or pep pill. Amphetamine consists of two enantiomers ... 

A chiral complex is one that is not identical to its mirror image. Thus, all optical isomers are chiral. The cis isomers of [CoCl2(en)2 + are chiral, and a chiral complex and its mirror image form a pair of enantiomers. The trans isomer is superimposable on its mirror image complexes with this property are called achiral. Enantiomers differ in one physical property chiral molecules display... 

Enantiomers differ in one physical property chiral molecules display optical activity, the ability to rotate the plane of polarization of light (Section 16.7 and Box 16.2). If a chiral molecule rotates the plane of polarization clockwise, then its mirror-image partner rotates it through the same angle in the opposite direction. 

Enantiomers have structures of exactly the same kind and yet are different. Their structures correspond to mirror images. In their physical properties they differ only with respect to phenomena that are polar, i.e. that have some kind of a preferred direction. This especially includes polarized light, the polarization plane of which experiences a rotation when it passes through a solution of the substance. For this reason enantiomers have also been called optical isomers. In their chemical properties enantiomers differ only when they react with a compound that is an enantiomer itself. 

Adenine as an isolated molecule has no symmetry elements and therefore might mathematically be considered chiral however, as in the case of glycine (Section 1.2.1), this description is not useful in chemistry since the enantiomers differ only by inversion through the weakly pyramidal nitrogen atom of the amine functionality, the main body of the molecule being planar. The inversion corresponds to a low-frequency vibration and a low-energy barrier such that single enantiomers... 

Enantiomers have identical chemical and physical properties in the absence of an external chiral influence. This means that 2 and 3 have the same melting point, solubility, chromatographic retention time, infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) spectra. However, there is one property in which chiral compounds differ from achiral compounds and in which enantiomers differ from each other. This property is the direction in which they rotate plane-polarized light, and this is called optical activity or optical rotation. Optical rotation can be interpreted as the outcome of interaction between an enantiomeric compound and polarized light. Thus, enantiomer 3, which rotates plane-polarized light in a clockwise direction, is described as (+)-lactic acid, while enantiomer 2, which has an equal and opposite rotation under the same conditions, is described as (—)-lactic acid. 

The calorimetric binding isotherms of the carbamoylated quinine and quinidine selectors clearly reveal that the heats released upon binding are strongly different for 5- and R-enantiomers of DNB-Leu, which is commensurate with the remarkable enantioselective molecular recognition capability of these selectors (Figure 1.14a,b). As can be seen from Table 1.4, the binding constants for R- and 5-enantiomers differ by about one order of magnitude in case of the carbamate-type selectors. Furthermore,... 

Bishydroxycoumarin (dicoumarol) is a natural occurring anticoagulant found in sweet clover. A number of coumarin derivatives have been synthesized as anticoagulants, warfarin, phenprocoumon and acenocoumarol being most frequently used. The nonpolar carbon substituent at the 3 position required for activity is asymmetrical. The enantiomers differ in both pharmacokinetic and pharmacodynamic properties. The coumarins are marketed as racemic mixtures. 

The first generation (G = 1) of the dendrimer series 5 was obtained without any difficulty using the described synthetic approach above. This open-shell compound exists in two interconvertible pairs of enantiomers differing in the helicity of the three propeller-like conformations adopted by each diphenylmethyl group. 

With molecules more complex than the gaseous anaesthetics, it is often the case that enantiomers differ not only in configuration, but also in conformation. The effect can be profound when the chiral centre is in a vinylic relationship as depicted by 48 or the aromatic equivalent 49. 

Determination of the odor character and intensity of enantiomers relies heavily on complete separation of the components of the sample where there is no coelution and baseline separation of enantiomers is seen (see Fig. Gl.4.4). If these ideal conditions are not met, considerable errors will be incurred in making odor measurements, particularly in cases where both enantiomers have similar odors, or where one is odorless. Traces of odorants coeluting with analytes under investigation, tailing of peaks, and low resolution all seriously affect chromatographic odor data. If the retention times of two enantiomers differ by <1 min, quantitative odor data may be inaccurate. 

If qualitative data are required, and the enantiomers differ significantly in their odorqual-ity, then acceptable results may be obtained. If odor intensity measurements (OAVs or OSVs) or threshold values are required, then the conditions described above must be obtained if the data is to be of value. Bernreuther et al. (1997) and Koppenhoefer et al. (1994) have published the enantiospecific sensory data for a variety of chiral odorants. 

The products of these transformations are pseudo enantiomers differing in absolute configuration and in mass, integration of the MS peaks and data processing affording the ee or E values. Any type of ionization can be employed, but electrospray ionization (ESI) is used most commonly [20,33-35]. An internal standard is advisable if it is necessary to determine percent conversion. The uncertainty in the ee value is less than 5%. In the original version about 1000 ee values could be measured per day [20a], but this has recently been increased to about 10 000 sam-... 

Pasteur showed that optical activity was related to molecular right- or left-handedness (chirality). Later, van t Hoff and LeBel proposed that the four valences of carbon are directed toward the corners of a tetrahedron. If the four attached groups are different, two arrangements are possible and are related as an object and its nonsuperimposable mirror image. Enantiomers differ only in chiral (or handed) properties, such as the direction of rotation of plane-polarized light. They have identical achiral properties, such as melting and boiling points. 

Plots of selectivity factor (calculated using Equation 2 and the data from Table I) for mephenytoin and hexobarbital enantiomers versus CD concentration are shown in Figure 3 a,b (22) The profiles of relation oC vs [(3-CD] for these two compounds are different because two different factors determine resolution of their enantiomers difference in K- values for hexobarbital and difference in kl t ftnn values for mephenytoin. The latter case represents 5nuinteresting example the resolution of its enantiomers arises from the great differentiation in the adsorption of diastereoisomeric (3-CD complexes. The calculated selectivity factor for these complexes is ca 3 (see Table I). In this particular case selectivities of the two processes adsorption and com-plexation in the bulk mobile phase solution are opposite to each other enantioselectivity arising from selective adsorption dominating over differentiation in the solution. Unfortunately the stabilities of diastereoisomeric -CD mephenytoin complexes are relatively small and solubility of -CD in the mobile phase solution is rather limited. Therefore one cannot shift the comple-xation equilibrium... 

Chirality is the origin of the spectroscopic property optical activity. The interaction of light and matter is characterized by the refractive index and the absorption coefficient. For chiral molecules, both the refractive index and the absorbance coefficient of one enantiomer differ for right and left circularly polarized light (r-cpl and 1-cpl). 

CE enantioseparations are commonly performed in the direct additive mode. The chiral selector is added to the background electrolyte (BGE) and undergoes stereoselec-tively complexation with the charged SA enantiomers. Different equilibrium constants of (/ )- and (S)-enantiomers and different mobilities of free and complexed solute species under the influence of the electric field are the basis for the differences in the observed migration times of the enantiomers. The indirect approach has only a little practical significance in this context. 

The method correlated well with both a high-performance liquid chromatography and an RIA procedure, with a slope approximating 1 in each case. The HPLC procedure at least measures both enantiomers. The most probable explanation of this result is that the enantiomers differ little in concentration in human plasma under the conditions of the experiment. Since racemic propranolol was used for generating the standard displacement curve, inability to detect the d isomer would be compensated for. 

As a result of an a.symmctrically substituted benzylic carbon. most of the aminoalkyl ethers are optically active. Moil studies indicate that the individual enantiomers differ signili-cuntly in antihistaminic activity, with activity residing predominantly in the S enantiomer. ... 

Ketamine, a dissociative anaesthetic, is administered as a racemic mixture (present in the parenteral preparation) and is initially metabolized by the liver to AT-desmethylketamine (metabolite I), which in part is converted by oxidation to the cyclohexene (metabolite II) (Fig. 1.5). The major metabolites found in urine are glucuronide conjugates that are formed subsequent to hydroxylation of the cyclohexanone ring. As the enantiomers differ in anaesthetic potency and the enantioselectively formed (metabolite I has approximately 10% activity of the parent drug) interpretation of the relationship between the anaesthetic effect and disposition of ketamine is complicated. On a pharmacodynamic basis, the S(+) enantiomer is three times as potent as the R(-) enantiomer (Marietta et al., 1977 Deleforge et al., 1991), while the enantiomer that undergoes N-demethylation (hepatic microsomal reaction) differs between species (Delatour et al, 1991). Based on the observed minimum anaesthetic... 

Table 4.6 Racemic drugs for which enantiomers differ in pharmacodynamic activity.

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