PhD Research Blog documenting PhD research

The backbone structure of the tambjamines is as follows:

It is expected that in the center of the molecule it would have a flat core due to the cyclic rings present and the delocalisation of the electrons. 

The prescence of an extra ring (which is conjugated) would be expected to extend the flat core.

3D structure of anisole (single ring) From PubChem

3D structure of prodigiosine (3 rings - including third NH in a ring) also has a flat core across the rings. (From Pubchem)

3D structure of tambjamine 33 - as calculated through Marvinsketch. Shows some distortion of the expected flat bicyclic core. 

This may be due to incorrect structure prediction from the drawing programs. Unfortunately most of the existing tambjamines (A, B, C, E, F, K, I do not have as many rings as many of the tambjamines in the new dataset).

Binding to Cl- ions appears to be on a 1 to 1 ratio with Hydrogen bonding between the 3 N-H groups present on the tambjamine and the Cl- ion. 

2 of the N-H groups come from the rings (in the protonated form) and the 3rd comes from the amine group or a 3rd ring (R2 position)

Image of proposed binding for tambjamines - source: page 163, Anion Recognition in Supramolecular Chemistry, Volume 24 of Topics in Heterocyclic Chemistry, ISBN 9783642154430

The binding of the chloride ion to the compound would be less likely to be affected by the sterics (unless the strained the planarity of the molecule), but would be more likely to be affected by electronic effects. 

The steric bulk of the molecule may affect its movement through the membrane though. A measurement of how wide the molecule is, or a ratio of maximum height to width could be plotted against the EC50 descriptor to look for a correlation.