For mass-limited samples the time needed to acquire the
necessary 2D NMR data in adequate quality can take several hours
or days even on high-field, ultra-sensitive NMR instruments. Also,
as already pointed out above, due to its molecular size the NMR
relaxation characteristics of bisindoles often complicate the measurement
of structurally informative NOEs, especially at higher
field strengths where spectral congestion tends to be less of a problem
(for a given structure and at a given field strength, the NOEs can
be either positive or negative, or can fall in between these regions,
depending on the solvent and on whether the bisindole is available
in base or salt form). Moreover, the NMR signal widths of bisindoles
often prove to be inconveniently broad due to the conformational
dynamics of the system, and/or possibly because of weak intermolecular
associations, and/or as a consequence of an acid-base
equilibrium being involved (velbanamine/vindoline-type bisindoles
contain two basic nitrogens, N(4) and N(4), with pKa1 ∼
7.5
and pKa2 ∼
5.5