Chiral Pharmaceuticals

• Type: Another Publication in an International Scientific Journal
• Date: 2016

Authors

Carla Fernandes (Author) FFUP; Madalena Pinto (Author) FFUP; Maria Elisabeth Tiritan (Author) FFUP; Rita Lado (Author) FEUP

Other information

Authenticus ID: P-00S-91B

DOI: 10.1002/0471238961.1608011823092009.a01.pub2

Abstract (EN): The word chirality originates from Greek “cheir,” meaning hand, which is a geometric property of any object that “cannot be brought to coincidence” with its mirror image. Chiral compounds are three-dimensional molecules with asymmetry in their structures. Thus, a chiral compound is one whose structure cannot be superimposed on its mirror image and both are entitled as enantiomers (Fig. 1) (1). The structure asymmetry is often originated by a stereocenter or stereogenic center (∗ ). The most common type of chirality is the tetrahedron carbon with four different groups of substituents or other atoms such as sulfur, phosphorous, and silicon (Figs. 2 and 3), which generate a stereogenic center (2). However, beyond central chirality, other elements of chirality are described such as planar, axial, and helical, found in structures without stereogenic centers (Fig. 4) (3,4). Enantiomers have identical thermodynamic and spectrometry properties, making the methodology to accurately quantify and identify them a challenge. Polarimetry through rotation of plane polarized light is the easiest and most conventional mode to differentiate enantiomers. They can be identified by rotation of the polarized light: for the right (clockwise) they are called dextrorotatory, (d) or (+), and for the left (counter-clockwise) they are denominated levorotatory, (l) or (
). Concerning their relative chemical configuration to the spatial orientation of the substituents of the stereogenic center, enantiomers can be (R), from the Latin rectus, or (S) from the Latin sinister. The equimolar mixture of both enantiomers is denominated racemate or racemic mixture and does not rotate the polarized light (5,6). Despite the similar thermodynamic properties in achiral context, enantiomers normally have different behavior when they face a chiral environment, such as biological systems or reactions in the presence of chiral catalysis. Biological systems are structurally chiral, as their essential subunits such as amino acids and carbohydrates, which form proteins, glycoproteins, and nucleic acids, have the so-called intrinsic chirality (7,8). Therefore, molecules that are the basis of biological processes in the living organisms, such as enzymes, receptors, or other binding molecules, can recognize enantiomers as different entities, leading to different biological responses (9). The molecular mechanism by which a chiral molecule, such as a macromolecule in a biological system or a chiral small molecule (in any process) can discriminate enantiomers by selective interactions is called chiral recognition. Enantiomers can have different pharmacokinetics and pharmacodynamics properties. Pharmacokinetics comprises absorption, distribution, and metabolism as well as excretion, while pharmacodynamics corresponds to the drug–receptor interaction resulting in bioactivity or toxicity. These phenomena can be different for two enantiomers (enantioselectivity) due to the chiral nature of membrane proteins, enzymes, and other chiral molecules, as a consequence of the different dissociation constants from the binding sites. Thus, enantioselective effects can often occur with enantiomers of chiral pharmaceuticals in pharmacokinetics events, in bioactivity, and/or in toxicity (9–12).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 28