View source for Polar surface area

{{more footnotes needed|date=December 2017}}[[Image:Paracetamol Electron Map.png|thumb|Electrical potential surface of [[paracetamol]] showing polar areas in red and blue]]

The '''polar surface area''' ('''PSA''') or '''topological polar surface area''' ('''TPSA''') of a [[molecule]] is defined as the surface sum over all [[chemical polarity|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 [[angstrom]]s squared (Å<sup>2</sup>) tend to be poor at permeating cell membranes.<ref name="Pajouhesh_2005">{{cite journal | vauthors = Pajouhesh H, Lenz GR | title = Medicinal Chemical Properties of Successful Central Nervous System Drugs. | journal = NeuroRx | volume = 2 | issue = 4 | pages = 541–553 |date=Oct 2005 | doi = 10.1602/neurorx.2.4.541 | pmid=16489364 | pmc=1201314}}</ref>  For molecules to penetrate the [[blood–brain barrier]] (and thus act on receptors in the [[central nervous system]]), a PSA less than 90 Å<sup>2</sup> is usually needed.<ref name="Hitchcock_2006">{{cite journal | vauthors = Hitchcock SA, Pennington LD | title = Structure - Brain Exposure Relationships | journal = J. Med. Chem. | volume = 49 | issue = 26 | pages = 7559–7583 |date=May 2006 | doi = 10.1021/jm060642i | pmid = 17181137 }}</ref>

'''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<ref>{{Cite journal |last=Shityakov |first=Sergey |last2=Neuhaus |first2=Winfried |last3=Dandekar |first3=Thomas |last4=Förster |first4=Carola |date=2013 |title=Analysing molecular polar surface descriptors to predict blood-brain barrier permeation |url=https://pubmed.ncbi.nlm.nih.gov/23428480/ |journal=International Journal of Computational Biology and Drug Design |volume=6 |issue=1-2 |pages=146–156 |doi=10.1504/IJCBDD.2013.052195 |issn=1756-0756 |pmid=23428480}}</ref>., 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<ref>{{Cite journal |last=Hester |first=Gabrielle |last2=Lang |first2=Tom |last3=Madsen |first3=Laura |last4=Tambyraja |first4=Rabindra |last5=Zenker |first5=Paul |date=January 2019 |title=Timely Data for Targeted Quality Improvement Interventions: Use of a Visual Analytics Dashboard for Bronchiolitis |url=https://pubmed.ncbi.nlm.nih.gov/30841007/ |journal=Applied Clinical Informatics |volume=10 |issue=1 |pages=168–174 |doi=10.1055/s-0039-1679868 |issn=1869-0327 |pmc=6402943 |pmid=30841007}}</ref> 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.<ref>{{Cite web |title=Δραστική: PARACETAMOL |url=https://farmako.net/el/drastikes/drastiki?SearchTerm=PARACETAMOL |access-date=2024-04-10 |website=farmako.net |language=en}}</ref>

==See also==
* [[Biopharmaceutics Classification System]]
* [[Cheminformatics]]
** [[Chemistry Development Kit]]
** [[JOELib]]
* [[Implicit solvation]]
* [[Lipinski's rule of five]]

==References==
{{Reflist}}

== Literature ==
* {{cite journal | doi = 10.1602/neurorx.2.4.541| pmid = 16489364| title = Medicinal chemical properties of successful central nervous system drugs| journal = NeuroRx| volume = 2| issue = 4| pages = 541–553| year = 2005| last1 = Pajouhesh| first1 = Hassan| last2 = Lenz| first2 = George R| pmc=1201314}} 
* {{cite journal | doi = 10.1021/js9804011| pmid = 10430547| title = Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption| journal = Journal of Pharmaceutical Sciences| volume = 88| issue = 8| pages = 807–14| year = 1999| last1 = Clark| first1 = David E}}
* {{cite journal | doi = 10.1023/A:1012188625088| pmid = 9165525| year = 1997| last1 = Palm| first1 = Katrin| title = Polar molecular surface properties predict the intestinal absorption of drugs in humans| journal = Pharmaceutical Research| volume = 14| issue = 5| pages = 568–71| last2 = Stenberg| first2 = Patric| last3 = Luthman| first3 = Kristina| last4 = Artursson1| first4 = Per| s2cid = 7178582}}
* {{cite journal | doi = 10.1021/jm000942e| pmid = 11020286| title = Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport Properties| journal = Journal of Medicinal Chemistry| volume = 43| issue = 20| pages = 3714–3717| year = 2000| last1 = Ertl| first1 = Peter| last2 = Rohde| first2 = Bernhard| last3 = Selzer| first3 = Paul}}
* Ertl, P. [https://books.google.com/books?id=wEsxCtyUJUEC&pg=PA111 Polar Surface Area], in ''Molecular Drug Properties'', R. Mannhold (ed), Wiley-VCH, pp.&nbsp;111–126, '''2007'''
* {{cite journal | doi = 10.1504/IJCBDD.2013.052195| pmid = 23428480| title = Analysing molecular polar surface descriptors to predict blood-brain barrier permeation| journal = International Journal of Computational Biology and Drug Design| volume = 6| issue = 1–2| pages = 146–56| year = 2013| last1 = Shityakov| first1 = Sergey| last2 = Neuhaus| first2 = Winfried| last3 = Dandekar| first3 = Thomas| last4 = Förster| first4 = Carola}}

==External links==
* [http://www.molinspiration.com/cgi-bin/properties Interactive Polar Surface Area calculator]
* [http://depth-first.com/articles/2007/09/19/easily-calculate-tpsa-descriptors-from-smiles-strings-using-ruby-cdk/ Free, Programmable TPSA Calculator]

[[Category:Cheminformatics]]
[[Category:Medicinal chemistry]]


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