ortho-Aminomethylphenylboronic acids are used in receptors for carbohydrates and various other compounds containing vicinal diols. The presence of the o-aminomethyl group enhances the affinity towards diols at neutral pH, and the manner in which this group plays this role has been a topic of debate. Further, the aminomethyl group is believed to be involved in the turn-on of the emission properties of appended fluorophores upon diol binding. In this treatise, a uniform picture emerges for the role of this group: it primarily acts as an electron-withdrawing group that lowers the pK a of the neighbouring boronic acid thereby facilitating diol binding at neutral pH. The amine appears to play no role in the modulation of the fluorescence of appended fluorophores in the protic-solvent-inserted form of the boronic acid/boronate ester. Instead, fluorescence turn-on can be consistently tied to vibrational-coupled excited-state relaxation (a loose-bolt effect). Overall, this Review unifies and discusses the existing data as of 2019 whilst also highlighting why o-aminomethyl groups are so widely used, and the role they play in carbohydrate sensing using phenylboronic acids.Physical organic chemistry is a discipline in which experimental and theoretical approaches are used to delineate reaction mechanisms, uncovering mother nature's chemical steps, physical phenomena and reactivity 1 . Many postulates, and sometimes heated debates, have been investigated and settled using the tools of this discipline. For example, the classic debate surrounding the norbornyl carbocation has only recently been settled with a low temperature (40 K) crystal structure 2 . Another is the controversy surrounding interpretation Reprints and permissions information is available at www.nature.com/reprints.

ortho-Aminomethylphenylboronic acid-based receptors with appended fluorophores are commonly used as molecular sensors for saccharides in aqueous media. The mechanism for fluorescence modulation in these sensors has been attributed to some form of photoinduced electron transfer (PET) quenching, which is diminished in the presence of saccharides. Using a well-known boronic acid-based saccharide sensor (3), this work reveals a new mechanism for fluorescence turn-on in these types of sensors. Compound 3 exhibits an excimer, and the associated ground-state aggregation is responsible for fluorescence modulation under certain conditions. When fructose was titrated into a solution of 3 in 2:1 water/methanol with NaCl, the fluorescence intensity increased. Yet, when the same titration was repeated in pure methanol, a solvent in which the sensor does not aggregate, no fluorescence response to fructose was observed. This reveals that the fluorescence increase is not fully associated with fructose binding, but instead disaggregation of the sensor in the presence of fructose. Further, an analogue of the sensor that does not contain a boronic acid (4) responded nearly identically to 3 in the presence of fructose, despite having no functional group with which to bind the saccharide. This further supports the claim that fluorescence modulation is not primarily a result of binding, but of disaggregation. Using an indicator displacement assay and isothermal titration calorimetry, it was confirmed that fructose does indeed bind to the sensor. Thus, our evidence reveals that while binding occurs with fructose in the aqueous solvent system used, it is not related to the majority of the fluorescence modulation. Instead, disaggregation dominates the signal turn-on, and is thus a mechanism that should be investigated in other ortho-aminomethylphenylboronic acid-based sensors.

Structural studies of a three-component assembly-a host and two distinct guests-were carried out using a combination of (11)B and (1)H NMR. In aprotic solvent, the imino group that forms ortho to the boronic acid or boronate ester group can form a dative N-B bond. In protic solvent, a molecule of solvent inserts between the nitrogen and boron atoms, partially ionizing the solvent molecule. Additionally, (11)B NMR was used in combination with a seventh-order polynomial to calculate five binding constants for each of the individual steps in protic solvent. Comparison of these binding constants was used to establish positive cooperativity in the binding of the two guests.

Overall molecular shape, rather than any specific noncovalent interactions, controls the preferential crystallisation of shapeshifting barbaralane isomers from dynamic mixtures.