Described herein are macromolecules modified with electrophilic groups and methods of making and using thereof. The preparation of a thiol-reactive, electrophililic derivative of HA in order to prepare “crosslinker-free” hydrogels are described as well as compounds and methods that are capable of coupling two or more molecules, such as macromolecules, under mild conditions. Specifically disclosed is the introduction of reactive bromo- and iodoacetate functionalities at the hydroxyl groups that are abundantly present on the HA polymer. The “crosslinker-free” hydrogels described have numerous applications including, but not limited to, drug delivery, small molecule delivery, wound healing, burn injury healing, tissue regeneration/engineering, cell culturing, and bio-artificial materials.