Polar surface area
Image:Paracetamol Electron Map.png|thumb|Electrical potential surface of paracetamol showing polar areas in red and blue
The polar surface area or topological polar surface area of a molecule is defined as the surface sum over all polar atoms or molecules, primarily oxygen and nitrogen, also including their attached hydrogen atoms.
PSA is a commonly used medicinal chemistry metric for the optimization of a drug's ability to permeate cells. Molecules with a polar surface area of greater than 140 angstroms squared tend to be poor at permeating cell membranes. For molecules to penetrate the blood–brain barrier, 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, the Placental Barrier, and the Blood-Mammary Barrier, 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 tend to permeate the BBB more easily, allowing them to reach the brain and exert their therapeutic effects.
Similarly, for drugs intended to treat the fetus, a lower TPSA is preferred to ensure they can pass through the placenta.
Breastfeeding mothers also need consideration. Here, an optimal TPSA for a drug is around 60-80 Ų to allow it to reach the breast tissue for milk production, while drugs exceeding 90 Ų are less likely to permeate the Blood-Mammary Barrier.
Literature
- Ertl, P., in Molecular Drug Properties, R. Mannhold, Wiley-VCH, pp. 111–126, 2007