What is the molecular weight limiting of molecules that can across lipid bilayer membrane??
Hi Mohammad,
that highly depends on the kind of molecule.
In general, Lipinski’s “Rule of 5” is one of the most influential frameworks correlating the physicochemical properties of a given compound with its membrane permeability and bioavailability in the context of small-molecules. It postulates that poor absorption or permeation is more likely when: (1) the calculated lipophilicity (clogP) is over 5; (2) the molecular weight is over 500; (3) there are more than five hydrogen bond donors (well represented by the sum of OH and NH bonds); and (4) there are more than ten hydrogen bond acceptors (represented roughly, by the sum of Ns and Os).
See: Article Getting Across the Cell Membrane: An Overview for Small Mole...
Hi,
I completely agree with Dominik. There is a famous review by Prof. Lipinski et al.
Article Experimental and computational approaches to estimate solubi...
which nicely describes this phenomenon and proposes the "Rule of 5" and afterwards it has been modified by many researchers. Mainly, some extra constraints have been added to the rules. The below paper desribes them all.Article The Rule of Five for Non-Oral Routes of Drug Delivery: Ophth...
Thanks Mr. Funken and Mr. Giri for your detailed and valuable answers as well as for recommending these interesting publications.
The famous rule of five is applicable for passive permeation. Did that include passive diffusion through protein transporters?? or it just describes the simple passive diffusion through the lipid bilayer ??
It regulates the permeation through the lipid membrane, not through the protein transporters. In case of protein channels and staffs like that several other factors come into play and some of the rules from so called "Rule of 5" are not applicable at all.
Do you have any idea how uncharged molecule like tetrakis(4-carboxyphenyl)porphyrin with high molecular weight (791>>>500) diffuse through plasma membrane?
- I exclude endocytosis because it normally occurs for charged molecules.
- Moreover, this molecule does not have plasma membrane specific transporter.
Any idea??
(See attached pic.)
Sorry, I do not have any idea. Please refer to the below articles:
http://pubs.rsc.org/-/content/articlehtml/2015/cc/c4cc09042j#cit4
Article Spectral- and time-resolved phosphorescence of photosensitiz...
https://www.nature.com/articles/nchem.120
Article DNA Damage and Apoptosis Induced by Photosensitization of 5,...
Article Singlet Oxygen in a Cell: Spatially Dependent Lifetimes and ...
Of course you will get the molecular specification from here: http://www.chemspider.com/Chemical-Structure.19980405.html
Beside Lipinski’s “Rule of 5, there are different areas in body where permeability is different for different molecules depending on type of pathway (protein channels "either leaky or gated"; carrier proteins 'either for passive or active transport'), molecular weight & size of molecule, number of receptors for the molecule and charge on molecules etc. That is why this rule is not fully defining the permeability in body, e.g. in kidney (glomerulus), molecules less than 9nm size can pass but when they are charged than smaller sized charged albumin (with a weight of 65,000 Daltons) molecule (which is negatively charged) is unable to pass completely.
Watch out if the uptake involves phase separation. Most transport studies in all cells and organelles magically transform during centrifugation nad a variety of energy fields due to changes in entropy. See our paper in PNAS, 1981. and many more after that.
The general rule is below 500 (MW), please look at the Lipinski rule and further publication by Riley and Barton ( A new paradigm for navigating compound property related drug attrition)
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