Questioning the wisdom of complexing NBOMe's with HPβCD

[Anon0631]

So I read here that β-cyclodextrin has a cavity diameter of 6-6.5 angstrom while λ-cyclodextrin has a cavity diameter of 7.5-8.3 angstrom.

I counted up the lengths of carbon-carbon, carbon-hydrogen and carbon-oxygen bonds across the widest part of the 25c-NBOMe molecule, applying Pythagoras calculations where necessary to account for angles and got a rough figure of 8 angstrom. This suggests that gamma-cyclodextrin might be a better candidate for complexing than beta-cyclodextrin.

Any thoughts?

 

[endotropic]

So I read here that β-cyclodextrin has a cavity diameter of 6-6.5 angstrom while λ-cyclodextrin has a cavity diameter of 7.5-8.3 angstrom.

I counted up the lengths of carbon-carbon, carbon-hydrogen and carbon-oxygen bonds across the widest part of the 25c-NBOMe molecule, applying Pythagoras calculations where necessary to account for angles and got a rough figure of 8 angstrom. This suggests that gamma-cyclodextrin might be a better candidate for complexing than beta-cyclodextrin.

Any thoughts?

Keep in mind the molecule probably doesn't exist in a fully extended conformation, but likely folds back at some point. Regardless, the widest part of the molecule doesn't have to fit through the cavity, it can slip in lengthwise. That link you gave also says, "β-cyclodextrin will complex aromatics and heterocyclic molecules" (e.g. 25C) while gamma is more appropriate for small peptides.

Theory aside, if the drug "works better" with β-cyclodextrin complexing, then there's not much point worrying about cavity diameters.

 

[Anon0631]

I assume it slips in 4-halogen-first seeing as that's the hydrophobic part of the molecule.