The polar surface area (PSA) or topological polar surface area (TPSA) of a

molecule A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

is defined as the surface sum over all

polar Polar may refer to: Geography * Geographical pole, either of the two points on Earth where its axis of rotation intersects its surface ** Polar climate, the climate common in polar regions ** Polar regions of Earth, locations within the polar circ ...

atoms or molecules, primarily

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

and

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

, also including their attached hydrogen atoms. PSA is a commonly used

medicinal chemistry Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with drug design, designing and developing pharmaceutical medication, drugs. Medicinal chemistry involves the identification, ...

metric for the optimization of a drug's ability to permeate cells. Molecules with a polar surface area of greater than 140

angstrom The angstrom (; ) is a unit of length equal to m; that is, one ten-billionth of a metre, a hundred-millionth of a centimetre, 0.1 nanometre, or 100 picometres. The unit is named after the Swedish physicist Anders Jonas Ångström (1814–18 ...

s squared (Å²) tend to be poor at permeating cell membranes. For molecules to penetrate the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

(and thus act on receptors in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

), a PSA less than 90 Å² is usually needed. TPSA is a valuable tool in drug discovery and development. By analyzing a drug candidate's TPSA, scientists can predict its potential for oral bioavailability and ability to reach target sites within the body. This prediction hinges on a drug's ability to permeate biological barriers. Permeating these barriers, such as the Blood-Brain Barrier (BBB), the Placental Barrier (PB), and the Blood-Mammary Barrier (BM), is crucial for many drugs to reach their intended targets. The BBB, for example, protects the brain from harmful substances. Drugs with a lower TPSA (generally below 90 Å²) tend to permeate the BBB more easily, allowing them to reach the brain and exert their therapeutic effects (Shityakov et al., 2013). Similarly, for drugs intended to treat the fetus, a lower TPSA (below 60 Å²) is preferred to ensure they can pass through the placenta (Augustiño-Roubina et al., 2019). Breastfeeding mothers also need consideration. Here, an optimal TPSA for a drug is around 60-80 Å² to allow it to reach the breast tissue for milk production, while drugs exceeding 90 Å² are less likely to permeate the Blood-Mammary Barrier.

References

Literature

* * * * * Ertl, P
Polar Surface Area
in ''Molecular Drug Properties'', R. Mannhold (ed), Wiley-VCH, pp. 111–126, 2007 *

External links

Interactive Polar Surface Area calculator

Free, Programmable TPSA Calculator
Cheminformatics Medicinal chemistry {{compsci-stub

See also

References

Literature

External links