Stereochemistry in medicine fields
Stereochemistry in medicine fields
Assist. Professor Dr. Muhammad H. J. Alajeely
Clinical Biochemistry Department
College of Medicine, Anbar University, Iraq
Louis Pasteur first identified optically active molecules in 1843 while separating tartaric acid crystallized sediments that had collected in wine vats. He found that the crystallized sediments were mirror images of one another, but had the same forms and chemical characteristics.
The same amount of rotation of light, albeit in the opposite direction, was also seen for the active molecules. One kind (laevorotatory) rotated polarized light to the left, whereas the other did so to the right (dextrorotatory). The "handedness" of tartaric acids was determined by X-ray crystallographic research in 1951, as well as the absolute configuration of each.
Handedness: Hand model, both mirror image of the other
Stereochemistry, sometimes known as the "chemistry of space," is the study of how atoms and groups are arranged spatially within molecules. It is crucial for drug activity since a drug's form affects how it interacts with the different biological molecules (enzymes, receptors, etc., its spatial configuration must be opposite for contact to complete reaction) that it comes into contact with in the body. Biochemists are particularly interested in stereochemistry because it affects how reactive and poisonous chemicals are. The majority of bodily reactions are stereospecific, which means that only molecules with particular atomic configurations will bind to receptor sites on cells.
The most frequent primary cause of stereoselectivity in pharmacokinetics is stereoselective metabolism of medicines. Enantioselectivity is the tendency of metabolizing enzymes to favor one enantiomer of a chiral drug over the other.
Groups of molecules with the same chemical formula but differing chemical structures are referred to as isomeric. Because distinct isomers may have various enzymatic and receptor affinities, changing their pharmacokinetic and pharmacodynamic properties, isomerism is important.
When a carbon atom has four different substituents, it is said to be an asymmetrical carbon atom and is symbolized as a center of asymmetry.
The molecules that are created when a chiral carbon splits into two mirror images are known as enantiomers. One of a drug's two enantiomers may have an intended positive impact while the other may have negative side effects, occasionally even positive but completely different effects. For instance:
While D-amino acids are not employed in the production of proteins, L-amino acids are
Usually, in case of macromolecules, such as polypeptides, proteins, DNA, etc., the whole molecule presents a conformational asymmetry; in this case, one can talk about intrinsic or helicoidal chirality. We can say that even the human body, if it were regarded as one molecule, has intrinsic chirality, on the inside and also on the outside, as we are not perfectly symmetrical.
A molecule's enantiomers are shown as the item and its mirror counterpart. In relation to glyceraldehyde, the stereochemistry of the D- and L- enantiomers is established. The chiral compounds are compared to glyceraldehyde as the reference standard since chemical modification has no effect on its configuration and because it has been used in the past for this purpose.
As only the L or D isomer of a given chemical exists, chiral versions of that molecule have distinct physiological effects, making D and L isomers significant in pharmacology. The isomers can now be created selectively as a result. This makes it possible to distribute chiral-molecule-containing medications in a way that is safer, more effective, and more focused.
Since there are two stereoisomers, they can also be referred to as enantiomers, which comes from the Greek words enántios, which means "opposite," and meros, which means "part." Optical activity is the term used to describe these molecules' capacity to rotate plane-polarized light by a same magnitude in opposing directions. A stereocenter is the location in a molecule that acts as the anchor for other groups of atoms to arrange themselves in space in such a way that any two groups' positions can be swapped.
Enantiomeric compounds, which have optical activity, are those that are biologically active. One such instance of an optically active molecule is a protein, with each of its two enantiomers being referred to as either L- or D-. When depicting the molecule in two dimensions, the identifier L- or D- is used.
Pharmacodynamics describes the physiological effects of a certain medication. First off, stereoisomerism affects how potent a medicine is. For instance, the l-form of propranolol has the required beta-blocking effect while d-propranolol is inactive. Second, stereoisomerism influences the pharmacological effects; methorphan is a good example of this.
The D- form reduces coughing, whereas the L form is a potent opioid analgesic. Thirdly, the therapeutic potential and negative consequences of stereoisomers vary. For instance, L ethambutol results in blindness but D ethambutol is used to cure tuberculosis. Finally, the efficacy of the stereoisomers can vary depending on how successfully the desired effect is generated.
These pharmacologic and pharmacokinetic consequences show that, often, one chiral form has the desired effect in the body whereas the other may have unfavorable or dangerous side effects or an entirely other impact.
As a result, medications created in a pharmacological setting must be enantiomerically pure, which means they must have the desired L or D enantiomer. One enantiomer products have the following advantages:
1. More specialized pharmaceutical items
2. A higher therapeutic index, which compares the dose of a medicine used for therapeutic purposes that has the intended effect to the dose at which it becomes toxic.
3. Less chance of drug interactions with other substances in the body
The discovery of new drug candidates is made possible by stereoisomerism, which also helps to improve the efficacy, safety, and potential of currently available medications. Enantiomerically pure medications have taken the place of several racemic mixes (combinations comprising both enantiomers), improving efficacy and lowering toxicity.
Ketamine, thiopentone, isoflurane, enflurane, desflurane, atracurium, mepivacaine, bupivacaine, tramadol, atropine, isoproterenol, and dobutamine are a few examples of chiral medicines used in anesthesia.
Currently, understanding isomerism has aided us in developing safer and more effective pharmacological substitutes for both newer and older medications. Many currently available medications have undergone a chiral transition, or a change from a racemic mixture to one of its isomers.