Bis-functional reagents

This approach offers unique opportunities for the generation of multi-functionalized cyclic 2-azadiene systems. A wide variation of the substitution pattern at the positions N-1 and C-6 can be determined by an appropriate choice of the aldehyde and amine. Various substituents can easily be introduced at the C-3 position via addition/elimination reactions on the sensitive imidoyl chloride moiety [24]. Upon reaction with bi-functional reagent, an adequately AT-protected 2(lH)-pyrazinone was elaborated into C-nucleoside analogues (Scheme 8). The desired skeleton and functionalities were obtained by oxidation-cyclization reaction followed by photochemical removal of the protective o-nitrobenzyl group [25]. 

With the aid of a bi-functionalized reagent (terminated with pyrenyl unit at one end and thiol group at the other end), gold nanoparticles were self-assembled onto the surface of solubilized carbon nanotubes [147], Raman spectrum of the gold nanoparticle bearing CNTs is enhanced possibly due to charge transfer interactions between nanotubes and gold nanoparticles. 

Despite these improvements, there are other important biosensor limitations related to stability and reproducibility that have to be addressed. In this context, enzyme immobilisation is a critical factor for optimal biosensor design. Typical immobilisation methods are direct adsorption of the catalytic protein on the electrode surface, or covalent binding. The first method leads to unstable sensors, and the second one presents the drawback of reducing enzyme activity to a great extent. A commonly used procedure, due to its simplicity and easy implementation, is the immobilisation of the enzyme on a membrane. The simplest way is to sandwich the enzyme between the membrane and the electrode. Higher activity and greater stability can be achieved if the enzyme is previously cross-linked with a bi-functional reagent. 

K Martinek, VP Torchilin. Stabilization of enzymes by intramolecular cross-linking using bi-functional reagents. Meth Enzymol 137 615-624, 1983. 

A large number of bi-functional reagents which form strong coordination complexes with metal ions have been investigated. These complexes are more soluble in non-polar organic solvents such as benzene or carbon tetrachloride than in the aqueous phase, and are therefore extractable. Of these compounds the fluorlnated... 

Another possible way to synthesize cross-hnked HA is by using bi-functional reagents. The cross-hnked HA product is synthesized after reaction of HA with dihydrazide in the presence of HOBT and carbodiimide (Eigure 5.3) [28]. In this reachon only the carboxylic functions from both HA molecules were used for cross-hnking. 

In cross-linking HA with bi-functional reagents like BDDE or DVS, first an aqueous solution of hyaluronan is prepared, into which the given quantity of the cross-linking agent... 

The problems of production and purification of hyaluronic acid are discussed in detail in Chapter 3. The comparable data of the commercial products are presented in Chapter 3 as well. The structure and rheological properties are discussed in Chapter 4. The discussion is united by a general idea about cooperative conformational transformations as the main phenomena that manifest bio-specificity of hyaluronic acid as well its unique effect of the relationships of biological properties from molecular mass. The physical and chemical methods of hyaluronan structural modification are presented in Chapter 5. It presents reactions of the macro-molecule cross-linking with bi-functional reagents as well as highly... 

Applications of these reactions to the construction of heterocyclic ring systems are wide and varied. Ring frameworks of all sizes and heteroatoms including oxygen, nitrogen, and sulfur are fully exemplified. One rapid access to isoquinoline ring systems is shown in the reaction of dialdehyde 150 with the bis-functionalized reagent 151 to produce 152 in 55% yield. ... 

If two or more ffinctional groups which should be protected occur in the molecule of the substrate, blocking can be accomplished with a bi-functional reagent, thus producing a cyclic product. Cyclic boronates, for example, can be used for the GC of compounds containing cM-diol groups in the 1,2- and 1,3-positions. 

Bi- or multi-functional reagents have been used to link enzymes to other proteins. These include various carbodiimides, bisdiazotized amines, cyanuric chloride and glutaraldehyde. Enzymes linked to rabbit IgG antibodies from sheep, goats, and horses are commercially available and greatly facilitate the ELISA procedure. The preparation of the antigen and the development of the corresponding rabbit antibody (IgG fraction) have been described previously. 

When a starch is treated with bi- or multi-functional reagents, crosslinking occurs. The reaction takes place in a slurry. With increasing degrees of crosslinking, starch... 

More recently, de Boer et al. (494, 495) have presented a detailed discussion of the binding modes of various mono- and bi-functional ethers with Pr (fod )3 and other Ln (fod )3 reagents. They specifically chose systems where a single type of adduct species predominates in solution. This circumvents having to perform the detailed statistical analysis of the shifts for systems containing appreciable amounts of species RS and RS2 which was found by Johnston et al. (489) to be necessary in order to obtain reliable association equilibrium constants and K 2 nd bound shifts (51 and 62. The binding scheme considered by de Boer et al (494) is shown in Fig. 9 (where L = R). It is noted that in addition to the... 

Either the solid support or the enzyme may be activated, but to limit disruption of the enzyme tertiary structure the functional groups of the support material are most often activated. The activation may occur prior to the coupling reaction (pre-activated supports), or a bi-functional linking reagent may be used to form the bond between... 

Reaction of methyl a-D-galactopyranoside 102.1 with 6,6 -bis(3,4-dihydro-2//-pyran) (bis-DHP, 1023) in refluxing chloroform (thermodynamic conditions) gives the dispoke (dispiroketal) derivative 102.2 in 64% yield. - The preference for rram-diequatonal protection is a consequence of steric interactions and multiple stabilising anomeric effects of the two acetal functions in the dispoke derivative. The pure bis-DHP reagent 1023 is a low melting solid (mp 49-50 C) that is stable at -10 °C in the absence of acid and moisture. It is prepared in 55% yield by the oxidative dimerisation of 6-lithio-3,4-dihydro-2//-pyr-an. As can be seen from Scheme 3.103, the preference for frum-diequatorial protection is excellent in the fiico, manno, and fyxo series but it is poor in the case of the arabino and rhamno series. 

The introduction of an azide functionality with CAN/NaNs as the reagents has been shown to be a useful transformation in organic synthesis. It also offers a convenient protocol for the bis-functionalization of a variety of alkenes. " The treatment of silyl enol ethers with sodium azide and CAN gives the a-azido ketones. The reactions of (substituted)styrenes with sodium azide and CAN in methanol under oxygenated conditions also furnish a-azido ketones (eq 21). With the aid of sodium iodide. 

Polyurethanes are generally synthesized by addition polymerization between a polyalcohol and a poly-isocyanate. This is an exothermic reaction caused by the release of a proton from the alcohol group followed by a general molecular rearrangement by the formation of the urethane bond [23], If both reagents are bi-functional linear polyurethanes are obtained, while if functionalities are increased some cross-linked chains are formed, with the formation of reticulated structures. In summary, one of the most common s mthesis routes for TPUs consists basically of the reaction of three main components. 

---