Broad band Fourier transform infrared spectroscopy was used to study the competition between hydrogen bonding and conformational and chemical changes in molecular nanoparticles. Particles of small carbohydrates (dihydroxyacetone, glyceraldehyde, fructose, and glucose) with sizes between 20 and 100 nm served as model systems. The variation of the preparation conditions allowed to control the chemical composition of the particles. For dihydroxyacetone, the particle generation in an electrospray is accompanied by the formation of intermolecular hemiketals. In contrast, particles generated directly from the vapor phase in a collisional cooling cell consist exclusively of the monomeric form. Quantum chemical simulations demonstrate that conformational changes upon particle formation can be understood to a good approximation on a molecular level. In contrast to that, the characteristic band shape observed for all carbohydrates studied is determined by the interaction of the whole ensemble of OH-oscillators. These contributions could be described within a continuum model.