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. Author manuscript; available in PMC: 2009 Feb 6.
Published in final edited form as: J Med Chem. 2008 Jun 26;51(12):3466–3479. doi: 10.1021/jm701478a

Table 5.

Computed Vacuolar Accumulation Ratios (VAR)

Compound/Vacuolar Accumulation Ratio (VAR)
DV pH CQ 8 13 18 22
CQR (pH 5.2) 2.3 × 104 2.3 × 104 1.9 × 102 1.7 × 102 7.9 × 104
CQS (pH 5.6) 3.7 × 103 3.7 × 103 6.7 × 101 6.4 × 101 5.0 × 103

VAR is calculated using the Henderson – Hasselbach equation and knowing cytosolic pH = 7.4, DV pH for CQR parasites = 5.2, DV pH for CQS = 5.620,2 and assuming: 1) that charged (protonated) drugs are essentially membrane impermeable; 2) net accumulation is not affected by binding to drug target. Although these are both simplifications, the calculated differences for (effectively) mono vs. diprotic drugs are orders of magnitude apart, whereas binding effects are expected to be (at most) several fold.