Optimization of Critical Parameters for Carbodiimide Mediated Production of Highly Modified Chitosan

Abstract

An optimization of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and hydroxy benzotriazole mediated conjugation of the polysaccharide chitosan with functional carboxylic acids was shown. Optimal parameters that enable resource-efficient synthesis of highly functionalized chitosan were identified. In particular, use of only catalytic instead of stoichiometric amounts of hydroxy benzotriazole and tight control of pH in reaction mixture resulted in highly efficient incorporation of the desired moieties as side chains in chitosan. As a result, the model reactant 4-azidobenzoic acid was incorporated resulting in a degree of substitution of over 30% with very high coupling efficacy of up to 90%. Similar results were obtained with other carboxylic acids such as methacrylic acid, 3-(2-furyl) propionic acid and 3-maleimido propionic acid, highlighting the broad applicability of our findings for the functionalization of chitosan.

Electrospinning and Photocrosslinking of Highly Modified Fungal Chitosan

“…[ 36 ] Used parameters were optimized for high DS at maximal coupling efficacy (CE). [ 33 ] A brief description of the method can be found in Figure S5 of the Supporting Information for the exemplified case of CS‐Az‐16‐Bio‐16. The molecular structure of CS, CS‐Az, and CS‐Az‐Bio is shown in Figure .…”

“…Modification of CS with substituents, containing carboxylic acid groups such as azide, biotin, or methyl red was accomplished using an amide coupling reaction facilitated by EDC and HOBt [33] based on the works of Matsumoto et al [36] Used parameters were optimized for high DS at maximal coupling efficacy (CE). [33] A brief description of the method can be found in Figure S5 of the Supporting Information for the exemplified case of CS-Az-16-Bio-16. The molecular structure of CS, CS-Az, and CS-Az-Bio is shown in Figure 1.…”

“…[ 32 ] CS‐Az with higher degree of substitution, which should further improve the water stability of nanofibers fabricated from it by electrospinning, is available by a recently developed more efficient method for chemical modification of CS. [ 33 ] The same modification method also enables introduction of other functional groups, such as specific affinity ligands for biomolecules, moieties suited for click‐chemistry, or pH‐responsive groups. [ 33 ] The ES process of these derivates has not yet been investigated and is thus a major focus of this work.…”

Chitosan–Hydroxycinnamic Acids Conjugates: Emerging Biomaterials with Rising Applications in Biomedicine

“…However, it is known that these reactions are pH-sensitive. It has been suggested that the pKa values of amino groups can be used to optimize the amidation [ 117 ], but it has also been reported that the use of cosolvents, such as dimethyl sulfoxide (DMSO), can cause changes in the apparent pKa value of the reagents, changing their properties in the reaction [ 118 ]. Therefore, the starting pH value and nature and amount of cosolvents, along with other parameters such as temperature, the ratio of molar equivalents, MW and DD of CS, and reaction time, should be considered when planning EDC-based reaction conditions.…”

Improvement of High-Throughput Experimentation Using Synthesis Robots by the Implementation of Tailor-Made Sensors

“…The computer is connected to a touch display that can be utilized to operate the analytical software [ 13 , 14 ]. This system is applicable in, for instance, reaction optimization by in situ measurements of pH value and temperature [ 15 ], air-quality tests by measuring CO 2 concentration [ 16 ], hydrogen detection during photocatalytic water splitting [ 17 ], and general chemistry education [ 13 , 14 , 18 ], for which it was originally developed.…”