Abiotic formation of hexoses and disaccharides in aqueous microdroplets

Understanding the chemical reactions that led to the origin of life is a fundamental challenge of chemistry. The formose reaction, an abiotic pathway to monosaccharides, provides a mechanism of sugar formation from simple aldehydes and ketones. However, the reaction requires the addition of base, metal catalysts, and is prone to side reactions, leaving questions about how such processes could have occurred on a primitive Earth. The abiotic formation of more complex sugars, such as disaccharides also require catalysts, and remains underexplored compared to other classes of biomolecules. This study investigates the role of microdroplets in the formation of hexoses and their subsequent condensation reactions to produce disaccharides, without the need for catalysts. The microdroplet-mediated synthesis of fructose and sorbose from glyceraldehyde or dihydroxyacetone, as well as that of disaccharides from various pentoses or hexoses, was monitored via mass spectrometery. Products were confirmed by high resolution mass spectrometry and tandem mass spectrometry. The product distribution of glucose disaccharides was determined by matching the relative intensities of product ions to a mixture of six disaccharide and showed a maximum yield of 9.4% or 1.7 µg min^-1 emitter. This study demonstrates the abiotic formation of monosaccharides and disaccharides, such as xylobiose and maltose, providing a possible link between prebiotic sugar synthesis and extant carbohydrate biochemistry. Hexose formation and disaccharide synthesis are driven by the unique air water interface of microdroplets, where partial solvation, pH extremes, and fast mass transfer kinetics enable abiotic transformations.