J. Am. Chem. SOC.1994,116, 3613-3614
"A Self-Replicating System": New Experimental Data
3613
Scheme 1
and a New Mechanistic Interpretation F. M. Menger,' Alexey V. Eliseev, and Nikolai A. Khanjin Department of Chemistry, Emory University Atlanta, Georgia 30322 Received October 26, 1993 Reuised Manuscript Received February 28, I994
Rebek and co-workers' described a self-replicating system depicted in Scheme 1. Amine 1 and ester 2 in chloroform react to form amide 4 uia complex 3. Reactants 1and 2 then combine with amide 4 to generate the termolecular complex 5, in which a catalyzed production of additional 4 takes place. The system can be considered "self-replicating" in the sense that amide 4 servesas a template for its own formation. "At best", the authors write of their autocatalysis, "this can be regarded as a primitive sign of life". In the ensuing article, we show that production of 4 is catalyzed by simple amides and that there is no need to postulate a "self-replication" mechanism since 4 itself contains an amide group. Evidence for autocatalysis came primarily from a ca. 40% enhancement of the initial rate when amide 4 was added externally to the reaction mixture. Strangely, a plot of [amide 41 us time taken over a long time period (1500 min) curved downward,2J indicating that the aminolysis actually slowed as the "product/ template" was being produced. Moreover, the plot leveled off at about 65% of thereaction. Rebeket al. speculated that the failure to reach completion was caused by ester hydrolysis in the chloroform solvent. Owing to these problems and to the rather small observed catalytic effect, we decided to reinvestigate the system. Reactionsbetween amine 1and ester 2 in CDCl3 were monitored by both 19Fand 1H NMR. NMR is a simpler and, in some ways, more informative method of assessing reaction progresscompared to the HPLC approach of Rebek et ai. Kinetic curves were obtained by periodically recording 19F (470MHz) and 1H (500 MHz) NMR spectra from solutions containingamine 1and ester 2 (both 0.03 M in CDC13)4plus triethylamine (0.12M) at 25.0 f 0.1 OC. Signals from pentafluorophenol (10.5 and 9.6 ppm) andfromamide4(5.26ppmoftheriboseH2'proton),respectively, were employed.5 Initial rates among repeat runs never deviated more than 6% from each other.6 The plot in Figure 1A of [C6F@H] us timegives an initial rate of 0.18 mM/min. When the experiment was repeated with the added presence of amide 4 as a "template" (1 equiv), the rate increased 56% to 0.28mM/min (Figure 1 B). Had we terminated (1) (a) Tjivikua, T.; Ballester, P.;Rebek, J., Jr. J. Am. Chem. Soc. 1990, 112, 1249. (b) Nowick, J. S.; Feng, Q.; Tjivikua, T.; Ballester, P.; Rebek, J., Jr. J. Am. Chem.Soc. 1991, 113, 8831. (2) Von Kiedrowski, G.; Wlotzka, B.; Helbing, J.; Matzen, M.; Jordan, S. Angew. Chem.,Int. Ed. Engl. 1991,30,423.Th*leauthorsdiscugsthesigmoidal curve with an induction period often seen with autocatalytic reactions. (3) See Figure 2 in ref lb. (4) This concentration, 2-fold greater than the highest used by Rebek,' had several advantages: (a) the precision of the data was improv6d; (b) the unidentified ride reaction was much less dominant than with Rebek's system (
