Buffer and Salt Effects in Aqueous Host–Guest Systems: Screening, Competitive Binding, or Both?

There are many open
questions regarding the supramolecular properties
of ions in water, a fact that has ramifications within any field of
study involving buffered solutions. Indeed, as Pielak has noted (Buffers,
Especially the Good Kind, Biochemistry, 2021, in press. DOI:10.1021/acs.biochem.1c00200) buffers were conceived
of with little regard to their supramolecular properties. But there
is a difficulty here; the mathematical models supramolecular chemists
use for affinity determinations do not account for screening. As a
result, there is uncertainty as to the magnitude of any screening
effect and how this compares to competitive salt/buffer binding. Here
we use a tetra-cation cavitand to compare halide affinities obtained
using a traditional unscreened model and a screened (Debye–Hückel)
model. The rule of thumb that emerges is that if ionic strength is
changed by >1 order of magnitudeeither during a titration
or if a comparison is sought between two different buffered solutionsscreening
should be considered. We also build a competitive mathematical model
showing that binding attenuation in buffer is largely due to competitive
binding to the host by said buffer. For the system at hand, we find
that the effect of competition is approximately twice that of the
effect of screening (∼RT at 25 °C). Thus,
for strong binders it is less important to account for screening than
it is to account for competitive complexation, but for weaker binders
both effects should be considered. We anticipate these results will
help supramolecular chemists unravel the properties of buffers and
so help guide studies of biomacromolecules.