Session: Posters:

There is evidence supporting the potential use of catechol-flavones for the treatment of neurological diseases such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and amyotropic lateral sclerosis. The compound 7,8-dihydroxyflavone has shown efficacy in laboratory models for each of these conditions. The catechol group is known to confer free radical scavenging activity, binding to divalent cations, and may be important for binding to certain proteins. For treatment of brain disorders, these compounds must be efficiently absorbed into the blood stream and translocated across the blood-brain barrier. The logarithm of the 1-octanol/water partition coefficient (LogP) is the most commonly used descriptor for predicting absorption, delivery, metabolism and excretion (ADME) properties. LogP for flavonoids can be calculated from the Abraham general solvation equation (AGSE) if certain measured parameters, such as the summation solute hydrogen bonding acidity (A), are known. The values of A for the mono-hydroxyflavones and mono-hydroxyisoflavones have previously been reported by this research group. For catechol (ortho-dihydroxy) groups, there is reciprocal intramolecular hydrogen bonding (IMHB) that diminishes the value of A for each hydroxyl group. For flavonoids, there is another complication due to IMHB between a hydroxyl group and the position 4 carbonyl group or the position 1 oxygen atom. The value of A for catechol has been determined from partition coefficients to be 0.88 but this parameter can also be estimated by measuring the ¹H-NMR chemical shift difference for the hydroxyl groups in DMSO-d₆ versus CDCl₃. The compound 5,6-dihydroxyflavone was sufficiently soluble in both solvents to determine the overall value of A as 0.56, which is lower than for catechol. All other catechol-flavones were insoluble in CDCl₃. An alternative approach using flavonoids with a methoxy group ortho to a hydroxyl group was used to estimate the values of A for the other catechol flavones. These values of A were then used to calculate LogP values by the AGSE.

Sara Tuck

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