Diboronic acids sensor

Yang W, Fan H, Gao X et al (2004) The first fluorescent diboronic acid sensor specific for hepatocellular carcinoma cells expressing sialyl Lewis X. Chem Biol 11 439 148... 

Sensor 9 provided the first structural elucidation of a diboronic acid sensor with o-glucose complexed within the binding site. The H NMR spectrum of this complex indicated that in deuterated methanol the o-glucose was bound in the a-pyranose form at the 1,2 and 4,6 positions, as in Figure 4." ... 

Wang and coworkers have documented a range of diboronic acid sensors (Figure 6a-z). It can be seen by examining the generic template used that the sensors are designed around the known core of sensor 9, the first diboronic acid sensor to display selectivity for o-glucose. 

Figure 6 Range of diboronic acid sensors (a)-(z) with the interchangeable linko- fragments highlighted in red, (f) displayed selectivity for sialyl Lewis X, and (g) displayed selectivity for D-glucose.

D-melibiose 339 M , while the monoboronic acid 28a has a binding constant of 96 in 52.1 wt% methanol-water at pH 8.21 (phosphate buffer). The selectivity of 27a-f for D-melibiose mirrors that for D-glucose, indicating that these diboronic acid sensors form stable 1 1 cyclic structures with the furanose segment of D-melibiose [84]. These observations and those of Hall with polysaccharides complement the observations made by Norrild for monosaccharides [13,14,85]. 

The D-fructose selective monoboronic add-based sensor 78 was enhanced by James in 1995 with the introduction of a second boronic acid group to form the diboronic acid sensor This Receptor-Spacer-Fluorophore-Spacer-... 

The recent evaluation of sensor 93, the first fluorescent diboronic acid sensor to be reported as a single-crystal X-ray structure both in its bound and unbound state, has recently been published. In the case of the unbound receptor, the geometry at boron is trigonal planar. This is important as the absence of deviation from planarity implies that there is no direct N-B Lewis base-Lewis acid bond at boron. 

From the pragmatic viewpoint of designing diboronic acid sensors with selectivity for D-glucose, many receptors have relied on an approximate spacing of the two boronic acid units such that the dimensions of the binding pocket mimic that of other established systems. 

To help visualise the trends in the observed stability constants (.Kobs) documented in Table 3, the observed stability constants (.Kobs) of the diboronic acid sensors 140( =3)-145( =g) are reported in Figure 30 divided by (i.e. relative to) the observed stability constants (. fobs) of their equivalent monoboronic acid analogue 146(pyrene)- In most cases, the observed stability constants (.Kobs) with diboronic acid sensors 140( =3)-145( =g) are higher than for the monoboronic acid sensor 146(pyrene)-... 

The observed stability constants (Kohs) for the diboronic acid sensors with d-fructose and o-mannose are, at most, twice as strong as with the monoboronic acid sensor 146(pyi.ene)- Each o-fructose and o-mannose molecule will only bind to one boronic acid unit through one diol. This allows complexes to form with... 

Figure 33 Observed stability constants (Kabs) of the diboronic acid sensors 140fn=3j-145fn—8) and the monoboronic acid reference compound 146(pyrene) (denoted n=ref) with the D-configuration of glucose and its derivatives.

The observed stability constants (.Kobs) for 140( =3) 145( =g) divided by the observed stabihty constants (Kobs) of 146(pyrene) are displayed in Figure 35. Overall the diboronic acid sensors retain their selectivity for D-glucose over the other saccharides. 

The observed stability constants ( obs) of sensor 147(phenanthrene pyrene) (with Xex=299 nm and >,ex=342 nm) were calculated by fitting the emission intensities at 417 nm V5. concentration of saccharide curves and are given in Table 5. The observed stability constants (A obs) for the diboronic acid sensor 147(phenanthrene pyrene) ( ex=299 and 342 um) with D-glucose were enhanced relative to those of the monoboronic acid reference compounds 146(pyrene) and 153(phenanthrene)> while the observed stability constants (Aobs) for the diboronic acid sensor... 

Figure 38 Generic template for the five diboronic acid sensors with variable fluorophore...

To help visualize the trends of the observed stability constants (. fobs) in Tables 7 and 8, the stability constants of the diboronic acid sensors 148(pyrene)-152(2-naphthaiene) arc rcportcd in Figurc 40 divided by the stability constants of the analogous monoboronic acid reference compounds... 

Figure 40 Observed stability constants (K hs) of the diboronic acid sensors 148(pyr j-152(2. ap/it/iaiene) divided by the observed stability constants (Kobs) of the corresponding monoboronic acid reference compounds (pyrene) l (phencmthrerte) (2-naphthalerte) iO yield relative ValueS With saccharides. The n-configuration of the monosaccharides was used throughout this evaluation.

Recently Wang and co-workers have documented a range of diboronic acid sensors Figure 42 It can be seen by examining the generic... 

Optimum D-glucose selectivity is obtained across the range of modular diboronic acid sensors 140( =3)-145( =g) when the two amine nitrogens are separated by a linker six carbon atoms in length. 

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