# How sure can we be about the structure of purine?

While answering the question Basicities of nitrogen atoms in purine, I noticed, that there might be a rapid interchange of the hydrogen bonded to the nitrogen atoms.
I have found a crystal structure in D. G. Watson, R. M. Sweet and R. E. Marsh, Acta Cryst. 1965, 19, 573-580. (DOI: 10.1107/S0365110X65003900, CCDCID: 1239746, 1239747), that resolves it as 1. However, at least in solution I would assume that there should be a distribution of structures according to the scheme below. In all cases the aromaticity is retained.

I am not an expert on crystal structures, and I don't know how to read the .cif file correctly. I remember from my course on crystallography, that the positions of hydrogen are notoriously hard to confirm.
Can we therefore really be sure about this structure? Is there evidence in the crystallography data for a large disordering?

To provide a bit more context, I am asking this, because it is likely to change part of the answer I have given to the linked question. If there exists an equilibrium between the above protomers, then that would certainly make it even harder to find the most basic nitrogen in purine.

• I'm not sure about crystallography, but $\ce{^{1}H}\text{-}\ce{^{15}N}$ HSQC experiments should be able to tell which nitrogen atom is associated to a proton (for example, here) and the extent of the contribution of each tautomer. – ralk912 Mar 16 '18 at 8:10
• For a small moleculesuch as this, crystal structure determination will give the positions of hydrogen with high certainty. However, equilibrium constant in the crystal might be different than in aqueous solution. For example, protonation of one nitrogen might be favored over another in the crystal because there is a hydrogen bond acceptor positioned in a favorable spot. – Karsten Theis Jan 16 at 17:58