Boronic acids binding

Shinkai et al. described the synthesis of dendritic saccharide sensors based on a PAMAM dendrimer labeled with eight boronic acid residues [183]. The dendritic compound showed enhanced binding affinity for D-galactose and d-fructose. The fact that the dendritic boronic acid functions as a saccharide sponge is ascribed primarily to the cooperative action of two boronic acids to form an intramolecular 2 1 complex. When one boronic acid binds a saccharide, its counterpart cannot participate in dimer formation and seeks a guest. 

Shinkai s group applied another method for the chiral spatial fixation of two porphyrins via peripheral substitution at the corresponding meso-position with boronic acid residue [67,68]. Thus, anionic 25 and cationic 26 formed an optically active 1 1 complex only in the presence of glucose and xylose in aqueous solution as a result of the boronic acid binding to the sac-... 

The boronic acid binding site can also be used for interactions with monoalcohols. In the presence of an ort/zo-hydroxymethylene group (see entry 1), an intramolecular cyclic monoester is formed (boronophthalide). This compound still has one hydroxyl group left for the esterification of monoalcohols, a reaction that can be used in the imprinting procedure [46,47,72]. Recently this method has been revived for the binding of steroid alcohols [73,986,c]. 

Bortezomib (velcade) (1R)-3-methyl-l-[[(2S)-1 -oxo-3-phenyl-2-[pyrazinylcarbonyl)amino] propyl]butyl]boronic acid binds to the 20S core of the 26S proteasome and reversibly inhibits its chymotrypsin-like activity. Inhibition of the proteasome disrupts multiple signaling cascades within the cell, often leading to cell death. The most important consequences of proteasome inhibition are believed to result from downregulation of NF-kB, a key transcription factor that promotes cell survival. In a similar manner, bortezomib disrupts ubiquitin-proteasome regulation of p2I, p27, and p53, which are key regulatory proteins in the cell cycle and initiators of apoptosis. 

Mostly templates with diol groups have been used. Templates can be bound by one boronic acid via a boronic ester bond. Imprinted polymers with higher selectivity are obtained if two boronic acid binding sites are attached to the templates as in most saccharide derivatives (see, e.g., Scheme 2). 

Boronic acid binding sites can also be used in combination with other covalent or noncovalent interactions. Glyceric acid and derivatives were thus bound as boronic esters aided by electrostatic, hydrophobic, charge-transfer interactions, or hydrogen bonding [39]. A boronic ester bond and a Schiflf base have been used for the imprinting of D-glyceraldehyde [4] and of l-DOPA in 8 [48]. 

Because of limited space, this chapter covers porphyrins and expanded porphyrins as receptors through mostly non-covalent or supramolecular interactions. As a general rule, examples wherein the porphyrin acts as a receptor via metal coordination are excluded. For a further reading on this latter topic, the reader is referred to a recent Chemistry Review article entitled Supramolecular Chemistry of Metallopor-phyrins. On the other hand, inspired by a recent review by Anslyn entitled Supramolecular Analytical Chemistry, we expand our definition of receptor-substrate interactions to include certain boronic acid binding motifs and several representative examples of metalated porphyrins that are applied to sensing applications, wherein the proposed mode involves metal complexation. Thus, included in this chapter is a brief summary of the seminal work carried out by Suslick and his group, where porphyrins are used to create the so-called artificial nose, that is, an array-based sensing device for various vapors. Also included are... 

Heinrichs G, Schellentrager M, Kubik S (2006) An enantioselective fluorescence sensor for glucose based rai a cyclic tetrapeptide containing two boronic acid binding sites. Eur J Org Chem 18 4177-4186... 

Scheme 5.1 Boronic acid binding equilibria for generic diols.

Takeuchi has prepared boronic acid dye 49 (Figure 12.12), which undergoes an absorption spectral change on addition of nucleosides [117]. The boronic acid binds with... 

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