Charged-induced conformational changes of sodiated poly(ethylene glycol) (PEG-(Na+)(n)) in a vacuum and water droplets were studied using molecular simulations. In a vacuum, compact and partially unwound conformations were identified by analyzing occupation probabilities on reaction surfaces defined by the accessible surface area of the macroion, the distance between the centers of mass of the PEG molecule and of the cations and radius of gyration of the macromolecule. The critical charge of the macromolecule for which there is coexistence of various conformations was estimated using the Rayleigh criterion for the breakdown of highly charged droplets and compared with that observed in the simulations. The simulation findings agreed well with the Rayleigh prediction. The properties of sodiated PEG macromolecules in the presence of solvent and ions were also investigated. It was found that the macroion becomes saturated with charge. The highly charged state leads to an extended conformation that is partially expelled by the droplet. However, a portion of the chain is still in contact with the solvent. Drying-out of the solvent leaves the macroion in a stretched necklace-like conformation. The mechanism of release of sodiated PEG from an aqueous droplet was shown to be distinctly different from that of a protonated polyhistidine in a water nanodroplet, demonstrating sensitivity of the disintegration mechanism of the nanodroplet to the degree of hydrophilicity of the macroion.