Table 1. COHb Half-life, Hemolysis, cLogP, and Aqueous Solubility for IRL Analogs 1, 2, 3, and 15–22.

	COHb t1/2 (min)a
compound	compound/Hb 20:1	compound/Hb 5:1	hemolysisb	cLogPc	aqueous solubilityd
1 (IRL 2500)	ND	69 ± 0.4	+	6.6	–
2 (IRL 1)	65 ± 0.5	74 ± 0.5	–	4.7	–
3	63 ± 0.5	ND	–	4.6	–
15	64 ± 0.4	69 ± 0.4***	–	6.5	–
16	60 ± 0.4***	71 ± 0.4***	+	5.9	–
17	77 ± 0.7	80 ± 0.7	–	4.1	+
18	57 ± 0.4***	72 ± 0.5**	–	4.4	–
19	69 ± 0.9	74 ± 0.5	–	4.6	+
20	71 ± 0.4	78 ± 0.7	–	3.9	+
21	65 ± 0.4	70 ± 0.5***	–	3.1	+
22	67 ± 0.4	72 ± 0.5***	–	3.5	–

^aCOHb half-life (t_1/2, shown as mean ± standard error) was measured at 20:1 compound/Hb (compound 200 μM and Hb tetramer 10 μM) or 5:1 compound/Hb (compound 50 μM and Hb tetramer 10 μM) in DPBS with 5 vol % DMSO. COHb t_1/2 with DMSO (as a control) was 80 ± 0.3 min. Significance relative to IRL 1 2: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. “ND” indicates half-life not determined.

^bHemolysis measured using RBCs (50 μM Hb) and compound (1 mM) in 0.1 vol % DMSO. “–” indicates that the fraction of extracellular Hb was less than 1% of total Hb after incubating blood with the compound.

^ccLogP calculated with ChemDraw BioByte.

^dSolubility was evaluated by preparing 2.5 mM of the compound in DPBS with 1 vol % DMSO. “+” indicates that aggregates or crystals were not observed in the prepared solution. “–” indicates that aggregates or crystals were observed.