Chiral inversion

2-Arylpropionic acid nonsteroidal anti-inflammatory drugs (NSAIDs) provide one of the best pharmaceutical examples of chiral inversion.

[5] When this happens, the configuration of the chiral molecule may rapidly change reversibly or irreversibly depending on the conditions.

It is well documented that (R)-enantiomers of profens in the presence of coenzyme A (CoA), adenosine triphosphate (ATP) and Mg+2 are converted to active (S)-forms.

[14][25] The pathway consists mainly of three steps: Because the acyl-CoA thioester (profenyl-CoA) changes the structure of triglycerides and phospholipids, metabolic chiral inversion may cause toxic effects.

[10] Chiral drugs with stereo-labile configuration are likely to undergo interconversion of the enantiomers that may be enzymatic (biological) or non-enzymatic.

The primary determinants of inter-individual variability in drug metabolism in humans are thought to include genetic polymorphism and a variety of other variables, including age, gender, biological conditions, pregnancy, illnesses, stress, nutrition, and drugs.

For instance, Reichel et al.[26] reported that a 2-arylpropionyl-coenzyme-A epimerase was molecularly cloned and expressed as a crucial enzyme in the inversion metabolism of ibuprofen.

[27] The liver, gastrointestinal tract (GIT), lungs, kidney, and brain are among the tissues that participate in the chiral inversion of medicines.

Because this process can change how chiral drugs work in the body and can cause side effects that can be serious or even fatal.

Traditionally, chiral inversions have been studied with NMR spectroscopy at different temperatures and chiroptical methods like polarimetry.

But strong, complementary methods based on dynamic chromatography (GC, HPLC, SFC, CEC, and MEKC) and electrophoresis have been made and used to figure out how the enantiomeric composition of stereo-labile chiral compounds changes over time.

This makes it useful for figuring out how pH, temperature, and solvents affect chiral inversion, which can happen on the stationary phase, in the injector, or in the detector.

Which instrument is used to analyze a chiral compound depends on its physical and chemical properties (i.e., the solubility, vapor pressure, thermal and solvent stability, and detection).

[29] For example, capillary electrophoresis or liquid chromatography could be used if the analyte can be ionized and has a high vapor pressure, but it is also soluble in polar solvents.

[31] On the other hand, gas chromatography is the best way to test a substance that is stable at high temperatures but has a low vapor pressure.