Measurement of optical rotation

For any measurement of optical rotation, the wavelength of the light used and the temperature must both be specified. In this case, D refers to the d line of sodium at 589 nm and 25 refers to a measurement temperature of 25°C. Calculate the concentration of a solution of L-arginine that rotates the incident light by 0.35° in an optical path length of 1 dm (decimeter). 

Figure 5.12 The principal working parts of a polarimeter and the measurement of optical rotation.

If an enantiomer is chemically pure it is possible to determine its degree of enantiomeric purity by measuring its optical rotation relative to a standard value, e.g if an enantiomeric mixture contains 1% of enantiomer A and 99% of enantiomer B [a] will be reduced by 2% compared to the value for optically pure B. Examples of the measurement of optical rotation as a quality control check are found in the BP monographs for Timolol maleate, Tobramycin and Phenylephrine Hydrochloride. 

Optical. - This adjective exclusively refers to measurements of optical rotation. It must not be used other than in the combinations optical rotation and optical purity. In particular, the terms optical resolution (better separation of enantiomers) and optical yield must be avoided. 

Optical Purity (op) - This measure of the composition of a mixture of enantiomers must not be applied, unless the composition was determined via measurement of optical rotation (see Section 1.2.2.2.) see Enantiomeric Purity. 

Optical activity is an associated phenomenon of chirality and has long been used to monitor the behavior of chiral compounds. Brief mention of this was made earlier (Section 5- 1C), but now the origin and measurement of optical rotation will be examined in more detail. 

Optical rotations usually are measured at just one wavelength, namely 589.3 nm, simply because sodium-vapor lamps provide an especially convenient source of monochromatic light. Measurements at other wavelengths are less easily made without specialized instruments, with which relatively few laboratories are currently equipped. Nevertheless, much information has been obtained about structure, conformation, and configuration of organic compounds from measurements of optical rotation as a function of wavelength (i.e., optical rotatory dispersion). 

Most of the research on optical rotatory dispersion to date has been with optically active ketones because the carbonyl chromophore conveniently has a weak absorption band in the 300 nm region. Compounds with chromophores that absorb light strongly in the ultraviolet usually are unsatisfactory for rotatory dispersion measurements because insufficient incident light is transmitted to permit measurement of optical rotation. Weak absorption bands below about 210 nm have not been exploited because of experimental difficulties in making the necessary measurements. 

Nuclease-(1-126) is inactive and appears to be disordered as judged by measurements of optical rotation, circular dichroism, and intrinsic viscosity 80). Nuclease-(127-149) is also inactive and does not bind to nuclease-(1-126) (80). Thus, the cleavage of the peptide bond between residues 126 and 127 destroys the functional structure of nuclease in contrast to the cleavage of bonds in the region of residues 48-50, which leaves the structure of nuclease essentially unchanged. 

Automatic spectropolarimeters are available for the measurement of optical rotation as a function of wavelength (in the region 180-700 nm), enabling optical rotatory dispersion (ORD) curves to be recorded. Models are also available (e.g. Japan Spectroscopic Co. Ltd) for the measurement of circular dichroism (CD) curves in the wavelength region of 180-1000 nm, and 700-2000 nm. Authoritative accounts of the value of ORD and CD data in studies on the structure... 

From the initial measurements of optical rotation through the present, a major goal has been the development of useful relationships between chiral-selective spectroscopic measurements and absolute structure. The most extensive early theoretical model of optical rotation was that of Kuhn and Bein in the 1930s.5 6 This strictly classical model was used to predict the sign of the optical rotation at the sodium-D line for the absolute structures of tris-bidentate chelated structures such as tris(ethylenediamine)cobalt(III) ion (Figure 5.2). Just as was the case for chiral... 

Determination.—Analytical methods for determination of D-glucuronic acid have been discussed recently by Artz and Osman.6 Decarboxylation is the most accurate method, and is generally used for determination of D-glucuronic acid from plant sources. Some modifications have been introduced recently for small quantities.26 Other methods, such as reduction, measurement of optical rotation, and an array of color tests,27 are of limited value. Levvy28 has applied a cerimetric method using a Conway burette. 

Chiroptical methods are widely used in the elucidation of the structure of steroid molecules [1-9]. Quantitative determination and control of the optical purity of drugs can also be solved by chiroptical methods, but they are rarely applied in pharmaceutical analysis. In pharmacopoeias, the only experimental measurements that are reported are optical rotations at the sodium D-line. These figures provide no specificity and relatively low analytical sensitivities. Nevertheless several papers have appeared in the literature where steroid determinations are based on the measurement of optical rotation [1,10-17]. The purpose of this chapter is to describe the applications of circular dichroism (CD) spectral measurements to the analysis of steroid molecules with particular emphasis to pharmaceutical preparations and drug forms. 

Tris-chelate complexes exist in enantiomeric configuration A and D about the metal atom, and when the chelating ligand is unsymmetrical, there are also geometrical isomers, cis and trans. Each geometrical isomer exists in enantiomeric forms thus there are four different molecules. In the case of tris complexes with symmetrical ligands, the process of inversion (interconversion of enantiomers) is important. When the metal ions are of the inert type, it is often possible to resolve the complex then the process of racemisation can be followed by measurement of optical rotation as a function of time. Possible pathways for racemisation fall into two broad classes those without bond rupture and those with bond rupture. 

Measurement of optical rotation is an important aid to detecting adulteration, as added compounds that might have been produced in bulk chemical synthesis will have chemicals with different optical activity from that of the natural oil. 

Concentration 0.4 in CHC13. Reference 11. Concentration 0.5 in CHC13. Reference 12. Solutions were too colored for accurate measurement of optical rotation. 

Consider now the application of this hydrogenation method to 2-[3-3H]ethyl 2-acetoxyacrylate, 160, with the introduction of two 2H atoms by the [Rh(/ )-prophos]+ catalyst. Since there is considerable evidence that these catalytic hydrogenations proceed in a syn fashion, there is a direct relationship between the newly developed configurations at both C-2 and the C-3 methyl group in 161. Moreover, if the absolute configuration at C-2 is known (and this follows from measurement of optical rotation) the absolute configuration of the chiral methyl group also follows. 

There is no special crystallization technique required to prepare chiral crystals from achiral organic compounds. Ordinary crystallization techniques can be employed i.e., a hot saturated solution of a compound in a suitable solvent is slowly cooled, or a saturated solution is slowly evaporated to obtain crystals. Whether the molecule is chiral can be easily differentiated by the measurement of optical rotation in solution using a polarimeter. However, there are great difficulties in measuring the optical rotation of crystalline substances due to the large birefringence [33]. Solid-state circular dichroism (CD) spectral measurements of... 

Several physicochemical methods of investigation, such as measurement of optical rotation (including optical rotation dispersion and circular dichroism) rheological methods, and X-ray analysis of fibers and films, have played a very important role for determination of conformations of galactan molecules and characterization of their supramolecular structures.8,19 As mentioned in Section I, only physicochemical methods used for determination of primary structures of polysaccharides are considered in this chapter. 

Polymer molecules in solution can be found in many different geometric conformations, and there exist a variety of experimental methods (e.g., viscosity, light scattering, optical rotation) for obtaining information about these conformations. In this experiment, the measurement of optical rotation will be used to study a special type of conformational change that occurs in many polypeptides. 

Chirality is most frequently studied by chiroptical methods. This term covers (1) measurement of optical rotation at a single wavelength, (2) measurement of optical rotation as a function... 

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