Adipic dihydrazide, abbreviated as ADH, is the most suitable hydrazide crosslinking agent. At room temperature and atmospheric pressure, Adipic dihydrazide appears as a white to slightly yellow solid and exhibits weak basicity. Because Adipic dihydrazide may cause coagulation if added directly to an emulsion in solid form, it is generally recommended that Adipic dihydrazide be first dissolved in hot water (as its solubility in cold water is poor) before use. Adipic dihydrazide is commonly employed as a homobifunctional crosslinking reagent specifically for aldehydes, forming relatively stable hydrazone linkages, and Adipic dihydrazide is particularly useful for coupling glycoproteins such as antibodies.

Figure1: Picture of Adipic dihydrazide

Synthesis process

The process conditions for the two?step synthesis of Adipic dihydrazide (ADH) have been investigated. In the first step, dimethyl adipate was synthesized via esterification of adipic acid with methanol, and in the second step, dimethyl adipate was hydrazinolyzed with hydrazine hydrate to obtain high?purity Adipic dihydrazide. The optimal conditions were determined as follows: for the esterification reaction, KHSO? was used as the catalyst at 5.5% by weight of adipic acid, with a molar ratio of methanol to acid of 4.0 and a reaction time of 1.0 h; under these conditions, the product dimethyl adipate reached a purity of 99.8% with a yield of 77%. For the hydrazinolysis reaction, the molar ratios of hydrazine to ester and methanol to ester were both 4.0, and the reaction time was 1.5 h; under these conditions, Adipic dihydrazide was obtained in 99% yield with a purity as high as 99.5%.

Adsorption effect on formaldehyde

The formaldehyde adsorption effect of Adipic dihydrazide in textiles was investigated using high?performance liquid chromatography–mass spectrometry to determine the Adipic dihydrazide content. Textile samples containing Adipic dihydrazide were placed in specific environments for a certain period to allow formaldehyde adsorption, and the formaldehyde content in the textiles was then measured by water extraction. The results showed that the maximum formaldehyde adsorption capacity of the samples increased with increasing Adipic dihydrazide content; however, when the Adipic dihydrazide content reached 1700 mg/kg, the maximum adsorption capacity no longer increased. For samples placed in a constant temperature and humidity environment, the formaldehyde adsorption reached its maximum after 30 days, whereas for samples placed in a common indoor environment shortly after renovation, the maximum adsorption was reached after 10 days, after which the samples gradually achieved an adsorption–desorption equilibrium. The surrounding environment did not affect the maximum formaldehyde adsorption capacity of Adipic dihydrazide?containing samples, but it significantly influenced the adsorption rate of Adipic dihydrazide?treated textiles and the time required to reach the adsorption–desorption equilibrium.

Modification on the performance of collagen

Collagen and hydrazide?functionalized hyaluronic acid derivatives were combined through gelation and subsequent crosslinking with genipin to form a composite hydrogel, and this study was undertaken to elucidate the influence of Adipic dihydrazide modification on the physicochemical and biological characteristics of the resulting collagen/hyaluronic acid scaffold. The investigation encompassed a comprehensive evaluation of scaffold morphology, mechanical properties, swelling behavior, and resistance to collagenase degradation, and the findings demonstrated that the overall stability of the composites was significantly enhanced by the combined application of Adipic dihydrazide modification and genipin crosslinking. Notably, Adipic dihydrazide provided a mild and effective means for functionalizing hyaluronic acid, thereby facilitating the creation of novel composite materials suitable for tissue engineering applications. The physicochemical assessments of the obtained scaffolds revealed that Adipic dihydrazide modification could substantially improve the crosslinking efficiency of genipin, which in turn led to increased mechanical strength, reduced water uptake, and a decreased degradation rate of the scaffolds. Furthermore, the retention and stabilization of hyaluronic acid within the composites were greatly improved through Adipic dihydrazide modification when combined with genipin crosslinking, and the results of preliminary cell culture experiments indicated that the Adipic dihydrazide?modified hyaluronic acid derivative might enhance chondrocyte adhesion, proliferation, and extracellular matrix secretion. Collectively, these findings suggest that the genipin?crosslinked collagen/hyaluronic acid scaffold incorporating Adipic dihydrazide modification, with its favorable stability and biocompatibility, holds considerable promise for applications in chondrogenesis.[1]

Reference

[1] Zhang L, Xiao Y, Jiang B, et al. Effect of adipic dihydrazide modification on the performance of collagen/hyaluronic acid scaffold[J]. Journal of Biomedical Materials Research Part B: Applied Biomaterials: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 2010, 92(2): 307-316.