Specific Optical Rotation | Specific Rotation (SOR) is an important property of chemical substances. A polarimeter instrument is required to determine the Optical Rotation and Specific Rotation. Select a suitable Analytical Method to determine the OR / SOR. Hence, the Analytical Method Development procedure is provided for reference purposes.
Specific Optical Rotation (SOR) Principle
Specific Optical Rotation (SOR) is a measure of the optical activity of a chiral compound. It is defined as the angle of rotation, in degrees, of plane-polarized light passing through a solution of the compound with a known concentration and path length. The specific optical rotation is expressed as degrees per unit length and concentration, typically in degrees per centimeter per gram per milliliter.
The specific optical rotation of a compound is a physical constant and is dependent on the molecular structure of the compound, the wavelength of the light used, and the temperature at which the measurement is made.
The specific optical rotation is useful in identifying and characterizing chiral compounds, particularly in the pharmaceutical industry. It can also be used to determine the purity of a sample, as the specific optical rotation of a pure compound is constant, while impurities or other stereoisomers may have different specific rotations.
The specific optical rotation is calculated using the following formula:
[α] = α / (l * c)where [α] is the specific optical rotation, α is the observed angle of rotation, l is the path length in decimeters, and c is the concentration of the compound in grams per milliliter.
Optical Rotation
Optical rotation is the phenomenon in which the plane of polarized light is rotated when it passes through a chiral compound. A chiral compound is one that has a non-superimposable mirror image, meaning that it exists in two different forms that are not identical.
The degree of rotation of the plane of polarized light depends on the concentration of the compound, the path length of the sample, the wavelength of light used, and the temperature. The rotation can be measured using a polarimeter, which consists of a light source, a polarizer, a sample tube, and an analyzer.
When plane-polarized light passes through a sample of a chiral compound, the electric field of the light wave causes the chiral molecules to rotate in a particular direction. As a result, the plane of polarized light is also rotated in the same direction. The amount of rotation is proportional to the concentration of the chiral compound in the sample.
The direction of rotation of the plane of polarized light depends on the configuration of the chiral molecule. If the molecule rotates the plane of polarized light to the right, it is said to have a positive rotation, designated as (+). If it rotates the plane of polarized light to the left, it is said to have a negative rotation, designated as (-).
Optical rotation is an important tool in chemistry and biochemistry for identifying and characterizing chiral compounds, determining their purity, and studying their behavior in solution and during chemical reactions. It is also used in the pharmaceutical industry to ensure the quality and consistency of chiral drugs.
Specific Rotation
Specific rotation is a measure of the extent to which a chiral compound rotates the plane of polarized light, per unit length of the sample cell and per unit concentration of the compound. It is expressed in degrees per unit length (usually decimeters) and per unit concentration (usually grams per milliliter) of the sample.
Specific rotation is a useful parameter in the characterization and identification of chiral compounds, as it is a physical property that is dependent on the molecular structure of the compound and the wavelength of the light used in the measurement. It is also useful for determining the enantiomeric purity of a sample, as enantiomers have the same magnitude of specific rotation but opposite signs of rotation.
The specific rotation of a chiral compound is calculated by measuring the angle of rotation of the plane of polarized light passing through a sample of known concentration and path length, using a polarimeter. The specific rotation is then calculated using the formula:
[α] = α / (l * c)where [α] is the specific rotation in degrees per unit length and concentration, α is the observed angle of rotation in degrees, l is the path length in decimeters, and c is the concentration of the compound in grams per milliliter.
The specific rotation of a chiral compound is a physical constant for a given compound, temperature, and wavelength of light, and can be used to identify and quantify the presence of chiral impurities in a sample. It is widely used in the pharmaceutical industry to ensure the purity and consistency of chiral drugs.
Difference between Optical Rotation and Specific Rotation
Optical rotation (OR) is the rotation of ‘plane-polarized’ light by a chemical substance. The rotation can be either clockwise (+) or counterclockwise (-). The measurement of the “Optical rotation” of a specific compound is called “Specific Rotation (SOR)”.
SOR instrument (Polarimeter)
The Optical rotation is measured with an instrument called a polarimeter.
Specific Rotation (SOR) Method Development
The minimum prerequisites for proceeding with Method development are Literature, Chemical Structure, Synthetic schemes, and Compound solubility.
Literature
Search for literature (USP, EP, JP, IP Chromatography Journals, patents, etc.,) for the same molecule or for similar molecules having similar structures. Check the availability of the solubility data (Physicians Desk Reference, www. Rxlist.com, etc.,).
Chemical structure
Based on the chemical structure and the Chiral center and the chiral plane ensure the optical rotation activity of the component.
Sample solubility
Check the solubility of the test sample in the solutions of common solvents like Methanol, Ethanol, and Acetonitrile, nonpolar solvents like Chloroform, Dichloromethane, a mixture of organic mineral acids like methanol HCl, Ethanol HCl, water-organic mixtures, etc. Ensure that the solution is stable for every hour.
Wavelength selection
Dissolve the compounds in the solvents at the concentration level of 0.1%, 0.5%, 1.0%, and 2.0% and measure the optical rotation at the Sodium lamp at the wavelength of 589 nm. If required check the optical rotation at the lower wavelength of 405 nm. Check the method precision by separately preparing the compound solution six times. Calculate the %RSD of the method precision. Check the solution stability by analyzing every 15 mins for the optical rotation. Check the linearity with varied test concentrations (at least 3-point linearity). Based on the precision, solution stability, linearity, and wavelength finalize the method.
Note: Lower wavelength is higher energy. So select the wavelength so as to get the comfortable reading about not less than 2° angle of rotation with the available sample concentration.
Specific Optical Rotation, [α] formula (or) SOR Calculation
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Note: Specific optical rotation depends on parameters like wavelength, medium, and sample temperature.
Specific optical rotation is independent of test concentration.
As per the existing method, if any turbidity is observed while preparing of sample solution, filter it and record the reading. While sending the report, mention the filtration details.
Calculate the SOR on an anhydrous (or) dried basis.
Selection of wavelength for Specific Rotation
In general the lower the wavelength, the higher the energy. Hence, the polarized light rotation will increase at the lower wavelengths. Hence experiment with lower test concentrations with lower wavelengths, so as to get the increased angle of rotation. So the precision of the results will observe a comfortable way.
Measuring of SOR for liquid samples: Measure the optical rotation against the air as blank or water and the same procedure shall capture in the Specification and Method of Analysis.
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Pharmacopeia Reference for Specific Rotation
The reference guide is available for Optical Rotation and/ (or) Specific Optical rotation. The details are as follows.
The USP General Chapters and Assays: Optical Rotation < 781>
Temperature requirements for SOR (or) OR, as per USP is 25°C
The European Pharmacopoeia: Physical and physicochemical methods <2.2.7>
Temperature requirements for SOR (or) OR, as per EP/ Ph.Eur. is 20°C
Refer to Jerry March, Organic Reaction Mechanism.