It is likely that 90% of all small-molecule high-performance liquid ch
romatography (HPLC) separations can be done with a hydrocarbon-bonded
phase of C4, C8, or C18 length using various mobile phases. The remain
ing 10% of the cases are more challenging. One solution is to follow t
he historical path of gas-liquid chromatography and create more bonded
phases. The second and more easily done is to add components to the m
obile phase that interact selectively with the molecules of interest a
nd change RPLC selectivity and retention. This paper begins with a gen
eralized discussion of additive strategy and mechanism and then leads
to a study of nonionic but coordinatively unsaturated (beta-diketonate
s as additives which serves as an example of the connection between mo
lecular chemistry and chromatographic selectivity and a review of othe
r work done. A system of coordinatively unsaturated metal beta-diketon
ates was investigated as mobile phase additives for HPLC. Unlike previ
ous ionic, metal dopants, these neutral complexes combine reasonable e
lution times, high chromatographic efficiency, and enhanced chromatogr
aphic selectivity for polar compounds in normal and reversed-phase mod
es. The influences of mobile-phase composition, stationary-phase subst
rate, and metal on solute retention behavior were examined for the met
al-dipivaloylmethane additive systems.