Hydrazides modification

The conversion of esters to hydrazides and of hydrazides to the sulfonyl derivatives occurs in good yield in the McFadyen-Stevens synthesis, but the decomposition of sulfonyl derivatives gives low yields of the desired products, for example, thiazole hydrazide (28) with 10% excess of PhSOjCl in pyridine gave a 75% yield of l-phenylsulfonyl-2-(4-methyl-5-thiazo ecarbonyl)hydrazine (29) (66). The Newman-Caflish modification of the McFadyen-Stevens synthesis gave 37% 4-methyl-5-thiazole-carboxaldehyde (30) (Scheme 27). 

Stmctural and chemical modification of urethane containing polymer matri-ces with macrocycles - calixarenes having reactive hydrazide groups have been carried out and stmcture, physico chemical and sensor properties of polyure-thanesemicarbazides (PUS) synthesised have been studied. The polymers obtained (on the base of polypropylene glycol MM 1000 and polysiloxane diol MM 860, hexamethylene diisocyanate and calixarene dihydrazide) are identified by IR-spectroscopy, size exclusion chromatography (SEC), DSC, WAXS and SAXS methods. 

Salicylohydrazide (1) reacts with acyl chlorides or acid anhydrides in the presence of meth-anesulfonic acid to give 1,3,4-benzoxadiazepin-5(4//)-ones 2 (Method A).317 A modification (Method B) consists of the condensation of the hydrazide 1 with ortho esters.317... 

Stereochemistry. - There has been a far infra-red spectroscopic study of ethyl phosphine,130 and in combination with X-ray fluorescence, further work completed on the conformational analysis of dialkylphenyl phosphines.131 The influence of water on the conformational equilibria of trimethyl phosphate has received attention.132 There has been a low temperature solid state and matrix isolation study of methyl phosphorodichi oridate,133 and a conformational study of polymorphic modifications of diphenyl-phosphinyl acetic acid hydrazide. 34... 

Figure 1.45 Reaction of bisulfite with cytosine bases is an important route of derivatization. It can lead to uracil formation or, in the presence of an amine (or hydrazide) containing compound, transamination can occur, resulting in covalent modification.

Most proteins contain an abundance of carboxylic acid groups from C-terminal functionalities and aspartic and glutamic acid side chains. These groups are readily modified with bis-hydrazide compounds to yield useful hydrazide-activated derivatives. Both carbohydrazide and adipic acid dihydrazide have been employed in forming these modifications using the carbodi-imide reaction (Wilchek and Bayer, 1987). 

Figure 1.112 Phosphate groups can be modified with adipic acid dihydrazide in the presence of a carbodi-imide to produce hydrazide derivatives. This is a common modification route for the 5 -phosphate group of oligonucleotides.

Modification of Amine or Hydrazide Molecules by Carbohydrates and Glycans... 

Add to the glycan solution the molecule to be labeled containing an available amine, hydrazine, or hydrazide group. For small molecule derivatization, the final concentration of the nucleophile in the glycan solution should be about 0.3 M to result in maximal efficiency of labeling. For protein modification, an aqueous reaction buffer should be used, and the protein should be as concentrated as possible. 

PDPH also may be used as a thiolation reagent to add sulfhydryl functional groups to carbohydrate molecules. The reagent can be used in this sense similar to the protocol described for AMBH (Chapter 1, Section 4.1). After modification of an oxidized polysaccharide with the hydrazide end of PDPH, the pyridyl group is removed by treatment with DTT, leaving the exposed sulfhydryl (Figure 5.15). 

Texas Red hydrazide is soluble in DMF and may be dissolved as a concentrated stock solution in this solvent prior to the addition of a small aliquot to an aqueous reaction medium. The solid and all solutions made from it must be protected from light to avoid photo-decomposition. Prepare the stock solution fresh immediately before use. A suggested protocol on the use of this fluorescent probe may be obtained by following the method outlined for fluorescein-5-thi-osemicarbazide in Section 1 of this chapter. Optimization may be necessary to achieve the best level of fluorescent modification (F/P ratio) for a particular application. 

Hydrazide groups react with aldehyde and ketone groups to form hydrazone linkages (Chapter 2, Section 5.1). Three BODIPY derivatives are available that contain a hydrazine group modification of carboxylate side chains. Biomolecules such as proteins that don t normally possess aldehyde residues can be modified to contain them by a number of chemical means (Chapter 1, Section 4.4). 

BODIPY 530/550 C3 hydrazide is insoluble in aqueous solution, but may be dissolved in DMF or methanol as a concentrated stock solution prior to addition of a small aliquot to a reaction. Coupling to aldehyde-containing molecules occurs rapidly with the formation of a hydrazone linkage. The reaction may be done in buffered environments having a pH range of 5-10. However, modification of glycoproteins with this fluorophore may not yield satisfactory... 

Figure 9.33 Modification of aldehyde-containing molecules can be done through this BODIPY derivative s hydrazide group.

Figure 17.4 Ketone derivatives of phenylalanine and mannose can be fed to cells to incorporate the monomers into proteins and glycans. The resultant modifications can be probed using hydrazide-containing reagents.

The following protocol describes a method for the periodate oxidation of a glycoprotein followed by biotinylation of the resultant aldehydes using hydrazide-PEG4-biotin. Chapter 1, Section 4.6 describes an alternative protocol for the modification of glycans at their reducing ends with hydrazide compounds. 

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