It is increasingly suspected that negative staining should be capable of imaging protein structure at much higher resolution levels than are usually achieved. The heavy metal salts traditionally used as negative stains give structural information only to 20-25Å (2.0-2.5nm); this limit probably is caused by several defective properties of these compounds. If new reagents without these defects can be identified, then higher resolution details should be imaged. The finding that some light atom salts can be used successfully for negative staining greatly increases the range of candidate compounds available for evaluation.

A covalently modified monosaccharide, glucose-6-phosphate, recently was shown to function as an unconventional negative stain. This natural organic reagent directly combines the desirable structurepreserving actions of glucose with added scattering from phosphorus and potassium atoms. It is not known if sugar derivatives containing other light atoms in place of phosphorus can serve as a negative stain.