Dipropinonates of Sugar Alcohols as Water-Soluble, Nontoxic CPAs for DMSO-Free Cell Cryopreservation

Sorbitol, mannitol, xylitol, and erythritol, four readily available sugar alcohols with poor or no membrane permeability, are converted into their corresponding dipropionates by acylating their primary hydroxyl groups. With enhanced membrane permeability, these diesters are expected to permeate the cell membranes and, upon their hydrolysis, release the corresponding sugar alcohols inside the cells. NIH-3T3 cells incubated with these diesters before being frozen at -80 °C exhibited considerably higher total recovery over those incubated with the free sugar alcohols or media only. Among the four diesters, those of sorbitol, especially mannitol, showed cryoprotective effects comparable to that shown by 5% DMSO. This work has demonstrated the feasibility of converting readily available, naturally occurring compounds into membrane-permeable derivatives that serve as water-soluble, nontoxic alternatives to DMSO.