PMC:6194691 / 52946-54472
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6194691","sourcedb":"PMC","sourceid":"6194691","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6194691","text":"There is, however, a danger in adopting this approach to the prediction of permeability. The use of linear free energy relations reveals correlations between the descriptors and the rate of transport, but unless used carefully it can obscure important features of the mechanism. For instance in the correlations reported for log(PS) [166, 167], the strongest correlation was a positive correlation between molecular volume and permeability, i.e. this approach seems to say that increases in molecular size result in increased permeability [160, 167]. However, the idea that bigger objects will be more permeable because they are bigger is completely counter-intuitive. The likely explanation for this paradox is simple. For the molecules considered in the correlations, increases in molecular volume were associated with large increases in lipophilicity as measured by Kn-octanol/water and it is plausible that it was the increase in lipophilicity that increased the permeability. Indeed as shown in Appendix C Abraham’s descriptor approach predicts for the compounds tested [166] that log[PS/Kn-octanol/water] varies much less than log[PS] and furthermore that it decreases when molecular volume is increased. In terms of Fig. 8, because large values of Kn-octanol/water are associated with large molecules, slopes less than 1 are expected if increasing molecular size has some effect that decreases permeability in addition to its effect that increases permeability by virtue of increasing Kn-octanol/water (see Appendix C).","tracks":[{"project":"MyTest","denotations":[{"id":"30340614-9466345-30706084","span":{"begin":334,"end":337},"obj":"9466345"},{"id":"30340614-15051171-30706085","span":{"begin":339,"end":342},"obj":"15051171"},{"id":"30340614-10696512-30706086","span":{"begin":540,"end":543},"obj":"10696512"},{"id":"30340614-15051171-30706087","span":{"begin":545,"end":548},"obj":"15051171"},{"id":"30340614-9466345-30706088","span":{"begin":1076,"end":1079},"obj":"9466345"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"30340614-9466345-30706084","pred":"source","obj":"MyTest"},{"subj":"30340614-15051171-30706085","pred":"source","obj":"MyTest"},{"subj":"30340614-10696512-30706086","pred":"source","obj":"MyTest"},{"subj":"30340614-15051171-30706087","pred":"source","obj":"MyTest"},{"subj":"30340614-9466345-30706088","pred":"source","obj":"MyTest"}]},{"project":"2_test","denotations":[{"id":"30340614-9466345-30706084","span":{"begin":334,"end":337},"obj":"9466345"},{"id":"30340614-15051171-30706085","span":{"begin":339,"end":342},"obj":"15051171"},{"id":"30340614-10696512-30706086","span":{"begin":540,"end":543},"obj":"10696512"},{"id":"30340614-15051171-30706087","span":{"begin":545,"end":548},"obj":"15051171"},{"id":"30340614-9466345-30706088","span":{"begin":1076,"end":1079},"obj":"9466345"}],"attributes":[{"subj":"30340614-9466345-30706084","pred":"source","obj":"2_test"},{"subj":"30340614-15051171-30706085","pred":"source","obj":"2_test"},{"subj":"30340614-10696512-30706086","pred":"source","obj":"2_test"},{"subj":"30340614-15051171-30706087","pred":"source","obj":"2_test"},{"subj":"30340614-9466345-30706088","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"MyTest","color":"#d593ec","default":true},{"id":"2_test","color":"#93ecbb"}]}]}}