Boronic Acid - Diol Complexation

A number of publications followed examining the properties and synthesis of boronic acids,with the first quantitative investigation into the interactions between boronic acids and polyols in 1959. In a study to clarify the disputed structure of the phenylboronate anion, Lorand and Edwards added a range of polyols to solutions of phenylboronic acid. The pH of the solutions was adjusted such that there was an equal speciation of phenylboronic acid in its neutral and anionic forms the pH matching the pK. As diol was added the pH of the systems decreased, allowing binding constants to be determined through the technique of pH depression. 

From these experiments, Lorand and Edwards concluded that the conjugate base of phenylboronic acid has a tetrahedral, rather than trigonal structure. The dissociation of a hydrogen ion from phenylboronic acid occurs from the interaction of the boron atom with a molecule of water. As the phenylboronic acid and water react, a hydrated proton is liberated, thereby defining the acidity constant K, see Hartley, Phillips and James. This is depicted in heme 5 by considering an explicit water molecule associated with the Lewis acidic boron. The reported pK s of phenylboronic acid fluctuate between 8.7 and 8.9, with a recent in-depth potentiometric titration study refining this value to 8.70 in water at 25°C.  

While one explicitly associated molecule is shown in a number of illustrative schemes for clarity, water should be considered to be in rapid exchange on the 

Lewis acidic boron in much the same way that hydrated Lewis acidic metal ions exchange bound water. A pertinent comparison can be found with the ionisation of Zn in water, the reaction Zn OH2 - Zn-OH + having a p.Ka of 8.8. Boronic acids have been reported to rapidly and reversibly interact with dicarboxylic acids,a-hydroxy carboxylic acids and diols to form esters in aqueous media.The most common interaction is with 1,2 and 1,3 diols to form five- and six-membered rings, respectively. From experimental observations, it is well known that the kinetics of this interconversion are fastest in aqueous basic media where the boron is present in its tetrahedral anionic form. Typically, differences in rate of 10 are observed between boron in its trigonal and tetrahedral forms.  

These phenomena were known and employed in analyte recognition for many years prior to an understanding of the mechanistic rationale behind the observed results. Although there are still various points of contention, a great deal of work has been conducted during the last few years, which has helped 

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G. Springsteen, B. H. Wang, A detailed examination of boronic acid-diol complexation, Tetrahedron 2002, 58, 5291. 

Freund has prepared polyaniline boronic acids by the electrochemical polymerization of 3-aminophenyl boronic acid [169, 170], The electrochemical potential of the polymer is sensitive to changes in the pK of the polymer as a result of boronic acid-diol complex formation. Fabre has also used polyaniline boronic acids as a con-ductiomeric sensor for dopamine [171]. 

Along this line, boronic acid-based polymer complexes are sensitive to glucose as a potential insulin delivery system, presumably due to the competitive binding of glucose to boronic acids, which disrupts the boronic acid-diol complex network within the polymer matrix (Scheme 13.5) [157]. In one study, the phenylboronic acid (PBA) moiety was attached to poly(M-vinyl-2-pyrrolidone) (NVP) to form poly(NVP-co-PBA)... 

Glucose-Responsive Systems Based on Boronic Acid-Diol Complexation... 

Rehybridisation of an sp boron complex to form the sp tetrahedral boronate species will therefore reduce the ring strain and lower the energy of the system. As a result it is thought that the dynamic equilibrium illustrated in Scheme 7 (and redrawn in Scheme 9 for clarity) between the neutral boronic acid diol complex 19 and the boronate anion diol complex 20 will shift to the right, causing the observed increase in the value of the acidity constant,... 

Over the period 2003-2004 the relationship between boronic acid diol complexation and acidity was studied computationally. Bock and co-workers... 

On complexation of a saccharide to a boronic acid there is a contraction of the O-B-0 bond angle with a concomitant increase in the addity of the boron species. Boronic acid diol complex formation is heavily pH dependent. Rate and stability constants increase by around four and five orders of magnitude, respectively, at pHs above the pA a of the boronic acid. 

On the basis of the simple boronic acid-diol reaction at the moleeular level, this chapter focuses on polymer-polymer interaetions triggered by boronic acid-diol esterification. When boronie aeid-diol reaetions oeeur cooperatively along a polymer chain, the structural changes caused by the complexation can easily amplify over hierarchies of nanometer to mierome-ter scale. Even without any signal such as fluorescence emission, the boronic acid-diol reaction based on precise molecular recognition is detectable as phase transition at the micrometer scale. 

Boronic acids can be incorporated into polymers in order to improve polymer-polymer interactions and develop polymer based materials. The incorporation of specific boronic acid-diol interactions, dramatically improves the polymer properties. Such that, structural changes caused by the complex-ation are amplified and readily detected. Details of polymer-polymer interactions prompted by the boronic acid-diol interaction are reviewed in this chapter by Numata. 

Figure 8 The compressed O-B-0 bond angle of the diphenylboronic acid - D-fructose complex" is found to be between the bond angles expected for sp and sp geometry, sp Geometry provides the closest match to the bound complex, meaning that formation of the tetrahedral boronate dial complex reduces ring strain and lowers the energy of the bound species. This results in a shift of the dynamic equilibrium between the neutral boronic acid dial complex 19 atui the boronate anion diol complex 20, causing the observed increase in the value of the acidity constant, Kf.

At low temperatures in inert solvents (such as methylene dichloride) a controlled polymerization can be effected using various acids and alkylating agents. These initiators include boron trifluoride etherate, triethylaluminum, trityl hexachloroantimonate, triethylam-monium hexachloroantimonate, diethyloxonium hexafluoroantimonate, p-toluenesulfonic acid and diethylzinc or cadmium-1,2-diol complexes. Crystalline, high molecular weight... 

Under alkaline conditions, boric acid (or at this pH, boron tetrahydrate) forms complexes with diols 11) The formation of such a complex between two polysaccharide molecules can lead to crosslinking. The use of borax can, therefore, be expected to increase the stability of the bonds between the hemicellulose and between the hemicellulose and cellulose fibers in the paper. 

Sugars, diol-containing compounds Neutral Boronic acid carrier Acid Covalently bound complexes Protonation of carrier [94,95]... 

The boronic acid functionality is being increasingly used in many ways to complex guests containing diols and carboxylic acid units. A few examples are described below. 

Few medicines based on boron are known, in general boric acid or a boronic acid serve to esterify an a-diol or an ortho-diphenol. This is the case for the emetic antimony borotartrates of the ancient pharmacopoieas, for the injectable catecholamine solutions, for tolboxane " , that is close to meprobamate and that was commercially available as a tranquilhzer some decades ago, or also for the phenylbo-ronic esters of chloramphenicol. " Boromycine was the first natural product containing boron isolated. " It is a complex between boric acid and a polyhydroxylated tet-radentate macrocycle. " Another natural product is aplas-momycin with antibiotic properties. " " ... 

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