. Author manuscript; available in PMC: 2021 Dec 30.

Published in final edited form as: J Chem Inf Model. 2020 Sep 16;60(10):4702–4716. doi: 10.1021/acs.jcim.0c00360

Table 2.

Reaction SMARTS Used by the Metabolite Prediction Algorithm

rule	reaction SMARTS
acetylation	[#7,#8,#16;h:1]≫[*:1][#6](=[#8])[#6]
azo splitting	[#7:1]=[#7:2]≫[:1].[:2]
benzodioxole reduction	[#6R:1]-[#8R:2]-[#6H2R:3]-[#8R:4]-[#6R:5]≫([:1]-[:2].[:3].[:4]-[*:5])
dealkylation	[#6H3:1][#7,#8H0,#16:2]≫([:2].[:1](=O)O)
	[#6H3:1][#7,#8H0,#16:2]≫([:2].[:1]=O)
	[#6H3:1][#7,#8H0,#16:2]≫([:2].[:1]-O)
	[#6H2:1][#7,#8H0,#16:2]≫([:2].[:1](=O)O)
	[#6H2:1][#7,#8H0,#16:2]≫([:2].[:1]=O)
	[#6H2:1][#7,#8H0,#16:2]≫([:2].[:1]-O)
	[#6H1:1][#7,#8H0,#16:2]≫([:2].[:1]=O)
	[#6H1:1][#7,#8H0,#16:2]≫([:2].[:1]-O)
	[#6H0:1][#7,#8H0,#16:2]≫([:2].[:1]-O)
	[#6:1][#6:2]≫(O-[:1].[:2])
	[#6h:1][#6:2]≫(O-[:1].[:2])
	[#6h:1][#6:2]≫(O=[:1].[:2])
	[#8H1:3]-[#6:1]-[#7,#8,#16:2]≫([:3]=[:1].[*:2])
dehydration	[#6,#7:1]-[#8H1:2]≫[:1].[:2]
	[#6:3]-[#6:1]-[#8H1:2]≫[:3]=[:1].[*:2]
	[#6,#7:1]=[#8:2]≫[:1].[:2]
dehydrogenation	[#16v4:1]-[Oh:2]≫[:1]=[:2]
	[#6h:1]-[#6D1H3,#6D2H2,#6D3H1,#7D2H1,#7D1H2,#7D3,#8H1:2]≫[:1]=[:2]
dephosphorylation	[#8:1]=[#15:2]([#8:3])([#8:4])[#8:5][#6:6]≫[:1]=[:2]([:3])([:4])[:5].O[:6]
epoxidation	[#6:1]=[#6,#7:2]≫[:1]1-[:2][O]1
epoxide opening	[#6:1]1[#8:2][#6:3]1≫([:2][:3][*:1])
	[#6:1]1[#8:2][#6:3]1≫([:2][:3][*:1]O)
glucuronidation	[#6:1][#6:2](=[O,N,P,S:3])[#8:4]≫O1C(C(=O)O)C(O)C(O)C(O)C([:4][:2](=[#8:3])[*:1])1
	[#8H1:1][#6:2]≫O1C(C(=O)O)C(O)C(O)C(O)C([:1][:2])1
glutathionation	[#6:1]1[#8:2][#6:3]1≫C(CC(=O)N[C@@H](CS([:1][:3][*:2]))C(=O)NCC(=O)O)[C@@H](C(=O)O)N
	[#6:1][Cl:2]≫C(CC(=O)N[C@@H](CS([*:1]))C(=O)NCC(=O)O)[C@@H](C(=O)O)N
	[#16h1:1]≫C(CC(=O)N[C@@H](CS([*:1]))C(=O)NCC(=O)O)[C@@H](C(=O)O)N
hydrogenation	[#6:1]#[#6:2]≫[:1]=[:2]
	[#6:1]=[#6:2]≫[:1]-[:2]
hydrolysis	[#8,#16:1]=[#6:2]-[#7,#8,#16:3]≫([:1]=[:2](O).[*:3])
	[#8,#16:1]=[#6:2]-[#7,#8,#16:3]≫([:1]=[:2].[*:3])
hydroxylation	[#6h:1]≫[*:1]O
	[#6h2:1]≫[*:1]=O
nitrogen oxidation	[#7v3:1]≫[*:1]O
	[#7v3:1]≫[*:1]=O
nitrogen reduction	[#7:1](=[#8:2])-[#8:3]≫[:1].[:2].[*:3]
	[#7:1]([#8:2]) [#8:3]≫[:1].[:2].[*:3]
	[#8:2]=[#7:1]-[#8:3]≫[:1].[:2].[*:3]
	[#8:2]=[#7:1]-[#8–1:3]≫[:1]=[:2].[*:3]
	[#7D2:1]=[#8:2]≫[*:1]
	[#7:1]-[#8:2]≫([:1].[:2])
oxidative dehalogenation	[#9,#17,#35,#53,#85:1]-[#6:2]≫[:1].[:2]O
	[#9,#17,#35,#53,#85:1]-[#6h1:2]≫[:1].[:2]=O
	[#9,#17,#35,#53,#85:1]-[#6H2:2]≫[:1].[:2](O)=O
	[#9,#17,#35,#53,#85:1]-[#6:2][#6H1:3]≫[:2](O)[:3]-[*:1]
	[#9,#17,#35,#53,#85:1]-[#6:2]-[#9,#17,#35,#53,#85:3]≫[:1].[:2](O)=O.[*:3]
	[#9,#17,#35,#53,#85:1]-[#6:2]-[#9,#17,#35,#53,#85:3]≫[:1].[:2](O)O.[*:3]
oxygen reduction	[#8:1]=[#6,#7:2]≫[:1]-[:2]
	[#8:1]-[#8:2]≫[:1].[:2]
reductive dehalogenation	[#9,#17,#35,#53,#85:1]-[#6:2]≫[:1].[:2]
	[#9,#17,#35,#53,#85:1]-[#6:2]-[#6:3]≫[:1].[:2]=[*:3]
sulfation	[#6:1][#8:2]≫[:1][:2]S(=O)(=O)O
	[#6:1]1=[#6:2][#6:3]2[#8:7][#6:4]2[#6:5]=[#6:6]1≫[:1]1=[:2][:3]=[:4](-S(C)(=O)(=O))[:5]=[:6]1
sulfur oxidation	[#16;v2,v4:1]≫[*:1]O
	[#16;v2,v4:1]≫[*:1]=O
sulfur reduction	[#16:1]=[#8:2]≫[:1].[:2]
	[#16:1]-[#16:2]≫[:1].[:2]

rule	reaction SMARTS
acetylation	[#7,#8,#16;h:1]≫[*:1][#6](=[#8])[#6]
azo splitting	[#7:1]=[#7:2]≫[:1].[:2]
benzodioxole reduction	[#6R:1]-[#8R:2]-[#6H2R:3]-[#8R:4]-[#6R:5]≫([:1]-[:2].[:3].[:4]-[*:5])
dealkylation	[#6H3:1][#7,#8H0,#16:2]≫([:2].[:1](=O)O)
	[#6H3:1][#7,#8H0,#16:2]≫([:2].[:1]=O)
	[#6H3:1][#7,#8H0,#16:2]≫([:2].[:1]-O)
	[#6H2:1][#7,#8H0,#16:2]≫([:2].[:1](=O)O)
	[#6H2:1][#7,#8H0,#16:2]≫([:2].[:1]=O)
	[#6H2:1][#7,#8H0,#16:2]≫([:2].[:1]-O)
	[#6H1:1][#7,#8H0,#16:2]≫([:2].[:1]=O)
	[#6H1:1][#7,#8H0,#16:2]≫([:2].[:1]-O)
	[#6H0:1][#7,#8H0,#16:2]≫([:2].[:1]-O)
	[#6:1][#6:2]≫(O-[:1].[:2])
	[#6h:1][#6:2]≫(O-[:1].[:2])
	[#6h:1][#6:2]≫(O=[:1].[:2])
	[#8H1:3]-[#6:1]-[#7,#8,#16:2]≫([:3]=[:1].[*:2])
dehydration	[#6,#7:1]-[#8H1:2]≫[:1].[:2]
	[#6:3]-[#6:1]-[#8H1:2]≫[:3]=[:1].[*:2]
	[#6,#7:1]=[#8:2]≫[:1].[:2]
dehydrogenation	[#16v4:1]-[Oh:2]≫[:1]=[:2]
	[#6h:1]-[#6D1H3,#6D2H2,#6D3H1,#7D2H1,#7D1H2,#7D3,#8H1:2]≫[:1]=[:2]
dephosphorylation	[#8:1]=[#15:2]([#8:3])([#8:4])[#8:5][#6:6]≫[:1]=[:2]([:3])([:4])[:5].O[:6]
epoxidation	[#6:1]=[#6,#7:2]≫[:1]1-[:2][O]1
epoxide opening	[#6:1]1[#8:2][#6:3]1≫([:2][:3][*:1])
	[#6:1]1[#8:2][#6:3]1≫([:2][:3][*:1]O)
glucuronidation	[#6:1][#6:2](=[O,N,P,S:3])[#8:4]≫O1C(C(=O)O)C(O)C(O)C(O)C([:4][:2](=[#8:3])[*:1])1
	[#8H1:1][#6:2]≫O1C(C(=O)O)C(O)C(O)C(O)C([:1][:2])1
glutathionation	[#6:1]1[#8:2][#6:3]1≫C(CC(=O)N[C@@H](CS([:1][:3][*:2]))C(=O)NCC(=O)O)[C@@H](C(=O)O)N
	[#6:1][Cl:2]≫C(CC(=O)N[C@@H](CS([*:1]))C(=O)NCC(=O)O)[C@@H](C(=O)O)N
	[#16h1:1]≫C(CC(=O)N[C@@H](CS([*:1]))C(=O)NCC(=O)O)[C@@H](C(=O)O)N
hydrogenation	[#6:1]#[#6:2]≫[:1]=[:2]
	[#6:1]=[#6:2]≫[:1]-[:2]
hydrolysis	[#8,#16:1]=[#6:2]-[#7,#8,#16:3]≫([:1]=[:2](O).[*:3])
	[#8,#16:1]=[#6:2]-[#7,#8,#16:3]≫([:1]=[:2].[*:3])
hydroxylation	[#6h:1]≫[*:1]O
	[#6h2:1]≫[*:1]=O
nitrogen oxidation	[#7v3:1]≫[*:1]O
	[#7v3:1]≫[*:1]=O
nitrogen reduction	[#7:1](=[#8:2])-[#8:3]≫[:1].[:2].[*:3]
	[#7:1]([#8:2]) [#8:3]≫[:1].[:2].[*:3]
	[#8:2]=[#7:1]-[#8:3]≫[:1].[:2].[*:3]
	[#8:2]=[#7:1]-[#8–1:3]≫[:1]=[:2].[*:3]
	[#7D2:1]=[#8:2]≫[*:1]
	[#7:1]-[#8:2]≫([:1].[:2])
oxidative dehalogenation	[#9,#17,#35,#53,#85:1]-[#6:2]≫[:1].[:2]O
	[#9,#17,#35,#53,#85:1]-[#6h1:2]≫[:1].[:2]=O
	[#9,#17,#35,#53,#85:1]-[#6H2:2]≫[:1].[:2](O)=O
	[#9,#17,#35,#53,#85:1]-[#6:2][#6H1:3]≫[:2](O)[:3]-[*:1]
	[#9,#17,#35,#53,#85:1]-[#6:2]-[#9,#17,#35,#53,#85:3]≫[:1].[:2](O)=O.[*:3]
	[#9,#17,#35,#53,#85:1]-[#6:2]-[#9,#17,#35,#53,#85:3]≫[:1].[:2](O)O.[*:3]
oxygen reduction	[#8:1]=[#6,#7:2]≫[:1]-[:2]
	[#8:1]-[#8:2]≫[:1].[:2]
reductive dehalogenation	[#9,#17,#35,#53,#85:1]-[#6:2]≫[:1].[:2]
	[#9,#17,#35,#53,#85:1]-[#6:2]-[#6:3]≫[:1].[:2]=[*:3]
sulfation	[#6:1][#8:2]≫[:1][:2]S(=O)(=O)O
	[#6:1]1=[#6:2][#6:3]2[#8:7][#6:4]2[#6:5]=[#6:6]1≫[:1]1=[:2][:3]=[:4](-S(C)(=O)(=O))[:5]=[:6]1
sulfur oxidation	[#16;v2,v4:1]≫[*:1]O
	[#16;v2,v4:1]≫[*:1]=O
sulfur reduction	[#16:1]=[#8:2]≫[:1].[:2]
	[#16:1]-[#16:2]≫[:1].[:2]