Table 6. Changes in Molecular Weight (MW), Hydrophobicity (log P), and Molecular Flexibility (Number of Rotatable Bonds) Associated with the Molecular Substitutions We Identified to Enhance GN activity or Permeation for ChEMBL Datasets 1 (pMIC) and 2 (Permeation).

			dataset 1				dataset 2
main moiety	+ /–	opposite moiety	pMIC repeats	ΔMW	Δlog P	Δno. rotatable bonds	permeation repeats	ΔMW	Δlog P	Δno. rotatable bonds
primary amine	addition	ether	225	–17.82	–0.13	–0.69	179	–18.88	–0.1	–0.7
primary amine	addition	carbonyl	655	–13.16	–0.13	–0.3	396	–17.54	–0.01	–0.35
primary amine	addition	secondary amine	2267	–13.61	–0.34	–0.94	2049	–14.29	–0.37	–1
lactone	removal	secondary amine	5	39.27	–0.16	0.6	3	44.74	0.19	0.33
lactone	removal	amine, tertiary	71	39.36	0.46	0.85	39	46.04	0.78	0.69
ester (carboxylate ester)	removal	secondary amine	21	4.37	0.28	–0.19	13	1.8	0.08	–0.31
ester (carboxylate ester)	removal	carboxamide	28	–21.43	–1.51	–2.21	26	–23.58	–1.59	–2.31
ester (carboxylate ester)	removal	ether	26	–0.97	0.39	0.27	13	1.25	0.13	0.38
ester (carboxylate ester)	removal	primary amine	36	–20.52	–0.19	–0.64	25	–17.18	–0.08	–0.76
ester (carboxylate ester)	removal	tertiary amine	106	37.1	0.48	0.42	51	31.21	0.49	0.25
carbonyl	removal	aryl chloride	48	0.96	0.58	–0.94	16	13.08	0.94	–0.88
nitrile	removal	ether	77	11.85	–0.13	1.01	34	13.28	–0.48	0.94
carboxamide	removal	thiophene	8	9.1	2.35	–1	1	75.92	2.33	–1
carboxamide	removal	carboxylic acid	42	–4.82	0.44	0.71	1	–0.00	1.48	0.00
carboxamide	removal	aryl chloride	5	–15	0.88	–1.2	2	–3.58	1.15	–1.5
thiophene	addition	aniline	16	–15.92	0.77	–0.75	6	–15.65	0.86	–0.67
thiophene	addition	carbonyl	39	40.18	1.34	–0.26	15	47.68	1.39	–0.4
tertiary carboxamide	removal	thiophene	5	11.13	2.11	–0.8	1	75.92	2.33	–1
tertiary carboxamide	removal	secondary carboxamide	35	–22.13	–0.62	0.83	13	–23.51	–0.57	0.54
aryl chloride	addition	nitrile	53	17.6	0.89	0	9	24.96	0.94	0
aryl chloride	addition	tertiary amine	52	2.07	1.15	–0.77	4	18.13	0.81	–1.25
aryl chloride	addition	aryl fluoride	291	16.1	0.55	0	49	14.46	0.55	0
secondary amine	addition	tertiary amine	1066	–15.1	–0.3	–0.05	755	–14.17	–0.33	0.07
secondary amine	addition	ether	203	–13.83	0.21	–0.28	150	–11.58	0.2	–0.3
secondary amine	addition	nitrile	62	4.03	–0.07	0.35	35	12.96	0.02	0.91
tertiary amine	removal	aryl chloride	52	2.07	1.15	–0.77	4	18.13	0.81	–1.25
tertiary amine	removal	alkanol	236	–21.80	–0.44	–0.22	99	–27.61	–0.69	–0.62
α,β-unsaturated carbonyl	removal	thiophene	11	50.58	1.07	0.45	6	56.97	1.33	0
α,β-unsaturated carbonyl	removal	secondary amine	25	–9.1	0.05	0.96	2	43.07	0.21	0
α,β-unsaturated carbonyl	removal	aryl chloride	7	28.52	0.75	0	2	30.48	0.7	0
aryl fluoride	addition	nitrile	64	–6.57	0.2	–0.03	16	–6.59	0	–0.06
aryl fluoride	addition	tertiary amine	56	–10.79	0.49	–0.91	17	–19.07	0.04	–1
aryl fluoride	addition	alkanol	81	7.36	0.74	–0.35	23	3.11	0.29	–0.61
average				3.67	0.43	–0.23		11.3	0.45	–0.37