FPIX monomers and dimers have different affinities for lipids. Lipids and/or monoacyl glycerols found within the DV provide convenient catalysts or scaffolds for the formation of Hz [24, 25] , and different quinoline drugs have different affinities for both monomer and dimer in aqueous solution. Thus, understanding heme monomer-dimer equilibria is essential [14] . De Dios and colleagues have recently explored pH and drug perturbations of the monomer-µ-oxo dimer equilibrium in some detail, and have also measured how this is influenced by drugs and micelles of different charge that, to a first approximation, model various possible lipid phases [26, 27] . In brief, remarkably, CQ is now known to favor binding to FPIX dimers whereas QN clearly favors the FPIX monomer [14] . In free solution, CQ actively promotes the formation of the µ-oxo dimer whereas QN stabilizes the monomer, both in a highly pH-dependent fashion [26] . Addition of a model lipid phase reveals pH-dependent lipid head group dependencies for monomer-dimer equilibria in the presence of quinoline drugs [27] . These are due to different aqueous versus lipid solubilities of monomeric versus dimeric FPIX, as well as different solubilities for these species complexed with quinoline drugs. This partitioning behavior is remarkably drug specific, even for related quinolines such as CQ compared with QN. Thus, even subtle changes in lipids or pH has profound effects on the efficiency of Hz production and has vastly different influences on the ability of even closely related drugs (e.g., CQ vs QN) to inhibit Hz formation. This makes sense since a nondrug-associated form of FPIX successfully partitioned into (or on) a lipid phase is likely to be essential for Hz production at the rate that has recently been directly measured in vivo [15] , and because drugs, pH and lipid composition individually and synergistically perturb FPIX-lipid partitioning. Evidenced by reciprocal patterns of CQ resistance versus QN resistance in some strains (see later), these data further highlight that CQ and QN are really quite different drugs, and that the design of inexpensive second generation quinolines active against CQR malaria should independently target CQ and QN pharmacophore scaffolds.