[GeauxTessa]

Hello all.  I'm having some trouble understanding how tertiary amines are able to cross lipid barriers such as the BBB and placenta when everything I read about tertiary amines relates that they're water soluble.  I understand that tertiary amines lack a protic hydrogen but this is all very confusing.  Is there any way someone could help me out with this concept?

[pgk]

Crossing lipid barriers is a question of molecular weight (or better: molar volume), lipophilicity and ionization degree (only the unionized form can cross lipid barriers). Thus, small tertiary amines penetrate thanks to their low molecular weight and higher tertiary amines thanks to their lipophilicity. Besides, tertiary amines have a lower pka compared to secondary ones and therefore, a lower ionization degree per concentration.

[GeauxTessa]

So how do tertiary amines have a lower ionization degree?  Because they can't make hydrogen bonds?

Thank you so much for your reply

[pgk]

Regardless the lack of proton, tertiary amines can form hydrogen bonds but this not the reason. There is a relationship between the pka and the ionization degree, in respect with concentration. It is a second order equation for concentrated solutions; while a first order aproximation for diluted ones, which is the given case in biological systems. Please, take a look to a textbook of general chemistry or analytical chemistry.

[Babcock_Hall]

Tertiary amines are hydrogen bond acceptors but not H-bond donors in their conjugate base form.  The issue of the pK_a valuesof tertiary amines has been vigorously debated here previously.

[pgk]

Thanks, Babcock_Hall for the better explanation of why tertiay amines can form H-bonds with the surrounding medium.