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2H, NH2), 3.76 (d, 3JP-H = 12.8 Hz, 3H, OCH3). 13C NMR (CDCl3), δC: 12.73 (d, 2JP-C
=
1
3.8 Hz, 1C, SCH3), 52.80 (d, 2JP-C = 5.7 Hz, 1C, OCH3). 31P{ H} NMR (CDCl3), δP: 37.40
(s). 31P NMR, δP: 37.40 (m). IR (KBr) (υ˜, Cm−1): 3300, 2860, 2840, 2540, 1550, 1430,
1200 (P O), 1030, 950 (P OCH3), and 780 (P NH2). GC MS (20 ev): retention time =
8.95 min; m/z (intensity (%)): 142 (100) (M+1)+, 141 (43) M+, 126 (18) [M CH3]+, 111
(8) [M OCH2]+, 110 (10) [M OCH3]+, 95 (32) [M SCH2]+, 94 (53) [M SCH3]+, 79
(8) [NH2PO2]+, 64 (25) [NH2POH]+, 47 (48) [SCH3]+, and 46 (27) [SCH2]+.
Ace, P(O)(NHCOCH3)(SCH3)(OCH3) (3). The solution containing acetamide (5
g, 0.071 mol) and THF (57 mL) was charged in a flask. Then potassium carbonate (12.28
g, 0.085 mol) was added. The obtained mixture was stirred for 30 min. Next, O,O-dimethyl
chlorothiophosphate was slowly added over a period of 15 min, and the mixture was then
refluxed at 60◦C for 12 h until the end of the reaction. It was then stirred for additional 35
min. The organic phase was separated, and the remaining product was purified with flash
chromatography (silica gel, n-hexane:ethyl acetate 8:2) to obtain colorless crystals:
1
Mp 86◦C; Yield: 63%. TLC (n-hexane:ethyl acetate (8:2, v/v)): Rf, 0.19. H NMR
4
3
(CDCl3), δH: 2.16 (d, JP-H = 1.5 Hz, 3H, CH3), 3.85 (d, JP-H = 12.5 Hz, 3H, OCH3),
2.38 (d, JP-H = 17.5 Hz, 3H, SCH3), 9.21 (brs, H, NH). 13C NMR (CDCl3), δC: 12.35
3
(d, 3JP-C = 6.3 Hz, 1C, CH3), 53.65 (d, 2JP-C = 6.3 Hz, 1C, OCH3), 24.05 (d, 2JP-C = 6.3
Hz, 1C, SCH3), 172.00 (s) (C, C(O)).31P{ H} NMR (CDCl3), δP: 29.18 (s). 31P NMR,
1
δP: 29.80 (m). IR (KBr) (υ˜, Cm−1) 3200, 1680, 1050 (P O C), 950 (P N C), and
1350 (P O). GC MS (20 ev): retention time = 6.41 min; m/z (intensity (%)):184 (10)
(M+1)+, 64 (13) [P(O)OH]+, 136 (59) [C3H7NO2]+, 94 (42) [P(O)(OCH3)NH2]+, 142 (17)
[(SCH3)(OCH3)P(O)NH2]+, 79 (28) [(CH3)P(O)]+, and 125 (23) [M NHC(O)CH3]+.
Computational Evaluation of Biological Activity
The biological activity spectra of DMPAT, Met, and Ace were obtained by PASS
(prediction of activity spectra for substances) software.17 This software is able to predict
900 synchronized biological activities based on the molecular structure of various com-
pounds. The biological activity spectra predicted by the PASS software are capable of
distinguishing pharmaceutical effects, side effects, biochemical reaction mechanism, ge-
netic mutation, carcinogenesis, toxicity fetus deficiency, and other biological activities of
chemical compounds.18 A portion of the predicted biological activity spectra for Met and
Ace is given in Table III (available online in the Supplemental Materials).
Lipophilicity Study
The rate of transport of a toxicant across cell membranes is directly proportional to
its lipid solubility. Water soluble compounds exhibit poor diffusion across lipophilic cell
membranes. Small hydrophilic compounds, however, may penetrate membranes through
aqueous pores. However, the total surface area of aqueous pores is small compared to the
overall lipid–domain surface area.4 In our research, logP values for the target compounds
were experimentally determined by the shake-flask method. Calculation of logP values
were performed as follows:19
logP = log{(y − x/x)(Vbuffer/Voct)}
(1)