Synthesis and characterization of adducts of alachlor and 2-chloro-N-(2,6-diethylphenyl)acetamide with 2'-deoxyguanosine, thymidine, and their 3'-monophosphates.
Adducts of the preemergence herbicide 2-chloro-N-(methoxymethyl)-N-(2,6-diethylphenyl)-acetamide (alachlor) and 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) with 2'-deoxyguanosine, thymidine, 2'-deoxyguanosine 3'-monophosphate, and thymidine 3'-monophosphate have been synthesized and characterized. Under mildly basic conditions alachlor and CDEPA form N-1 adducts with 2'-deoxyguanosine and N-3 adducts with thymidine as a result of chlorine displacement. In addition, alachlor formed an N-7 adduct with 2'-deoxyguanosine, 7-[[(N-(methoxymethyl)-N-(2,6-diethylphenyl)carbamoyl]methyl]guani ne. N-1 adducts of alachlor and CDEPA with 2'-deoxyguanosine 3'-monophosphate and N-3 adducts with thymidine 3'-monophosphate are also described. In addition to spectroscopic data, structural proof included the dephosphorylation of each nucleotide adduct to its corresponding nucleoside adduct by nuclease P1. Alachlor and alachlor adducts but not CDEPA and CDEPA adducts exhibited rotational isomerism as evidenced by proton and 13C NMR studies. These rotamers were attributed to hindered rotation about the shortened N-carbonyl bond. Computational methods employing molecular mechanics and quantum mechanics were used to characterize the structures and energies of these rotamers to account for the patterns of duplicate NMR resonances observed.
Nesnow
S
S
Carcinogenesis and Metabolism Branch (MD-68), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Agarwal
S C
SC
Padgett
W T
WT
Lambert
G R
GR
Boone
P
P
Richard
A M
AM
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry; D000083:Acetanilides / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010710:Phosphates / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013936:Thymidine / Q000737:chemistry*
D000081:Acetamides; D000083:Acetanilides; D010710:Phosphates; C000188:alachlor; C093872:2-chloro-N-(2,6-diethylphenyl)acetamide; D003849:Deoxyguanosine; D013936:Thymidine