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33646510315
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note
-
(b) Note that covalently bound enzyme-substrate complexes are generally not invoked as intermediates in terpenoid synthase catalyzed reactions, and the putative carbocation rearrangements involved are generally formulated as involving noncovalent enzyme-substrate interactions (steric and/or electrostatic).
-
-
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19
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(f) Cane, D. E.; Abell, C.; Lattman, R.; Kane, C. T.; Hubbard, B. R.; Harrison, P. H. M. J. Am. Chem. Soc. 1988, 110, 4081-4082.
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(e) The value of diffuse functions in density functional based calculations was recently discussed in: Lynch, B. J.; Zhao, Y.; Truhlar, D. G. J. Phys. Chem. A 2003, 107, 1384-1388.
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Recent reports on the application of the B3LYP method to carbocations (with leading references to others) include: (a) Smith, W. B. J. Org. Chem. 2001, 66, 376-380.
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(c) Müller, T.; Juhasz, M.; Reed, C. A. Angew. Chem., Int. Ed. 2004, 43, 1543-1546.
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(d) Matsuda, S. P. T.; Wilson, W. K.; Xiong, Q. Org. Biomol. Chem. 2006, 4, 530-543.
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(h) Farcasiu, D.; Lukinskas, P.; Pamidighantam, S. V. J. Phys. Chem. A 2002, 106, 11672-11675.
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33646504876
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See also ref 2
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(k) See also ref 2.
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48
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18844458354
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(a) Gutta, P.; Tantillo, D. J. Angew. Chem., Int. Ed. 2005, 44, 2719-2723.
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(b) Ponec, R.; Bultinck, P.; Gutta, P.; Tantillo, D. J. J. Phys. Chem. A 2006, 110, 3785-3789.
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Ponec, R.1
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-
50
-
-
33646524752
-
-
note
-
(c) With zero-point energies included, the transition structure preceding 8 is actually 0.07 kcal/mol lower in energy than 8 with B3LYP/6-31+G(d,p) and 0.81 kcal/mol higher than 8 with mPW1PW91/ 6-31+G(d,p)//B3LYP/6-31+G(d,p), and the transition structure following 8 is 0.98 kcal/mol higher in energy than 8 with B3LYP/6-31+G(d,p) and 2.00 kcal/mol higher than 8 with mPW1PW91/6-31+G(d,p) //B3LYP/ 6-31+G(d,p).
-
-
-
-
53
-
-
33646536591
-
-
note
-
(c) IRC plots are available in the Supporting Information.
-
-
-
-
54
-
-
18844424379
-
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molecular graphics application for MacOS computers, Johannes Kepler University, Linz
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Müller, N.; Falk, A. Ball & Stick V.3.7.6, molecular graphics application for MacOS computers, Johannes Kepler University, Linz, 2000.
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Ball & Stick V.3.7.6
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Müller, N.1
Falk, A.2
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55
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0030751628
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2+; see, for example, ref 6. Kinetic studies on related sesquiterpene synthases have suggested that this ionization may be the slow chemical step in such reactions; see: Cane, D. E.; Chiu, H.-T.; Liang, P.-H.; Anderson, K. S. Biochemistry 1997, 56, 8332-8339
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Biochemistry
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Cane, D.E.1
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and Mathis, J. R.; Back, K.; Starks, C.; Noel, J.; Poulter, C. D.; Chappell, J. Biochemistry 1997, 56, 8340-834.
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Mathis, J.R.1
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Poulter, C.D.5
Chappell, J.6
-
57
-
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33646500111
-
-
in press
-
(b) Based on recent experimental (isotope effect) studies, it has been suggested that a discrete farnesyl cation may be avoided in a related cyclization reaction of farnesyl diphosphate: the enzyme catalyzed formation of premnaspirodiene via the germacradienyl cation. See: Schenk, D. J.; Starks, C. M.; Rising Manna, K.; Chappell, J.; Noel, J. P.; Coates, R. M. Arch. Biochem. Biophys., in press.
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Arch. Biochem. Biophys.
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Schenk, D.J.1
Starks, C.M.2
Rising Manna, K.3
Chappell, J.4
Noel, J.P.5
Coates, R.M.6
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58
-
-
33646500573
-
-
note
-
A competing [1,2] methyl shift leading to other products is also possible. This reaction and others that may follow it will be described in detail in a separate account.
-
-
-
-
59
-
-
33646507903
-
-
note
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(a) Cationic [1,2] hydrogen or alkyl shifts generally have very low activation barriers, and in some cases, bridged hypercoordinate structures are actually minima rather than transition structures (so-called nonclassical ions). For leading references, see ref 17.
-
-
-
-
60
-
-
33646513751
-
-
note
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(b) A small amount of ring strain in the 1-to-2 transition structure likely contributes to the barrier of 6 kcal/mol that we observe in this case.
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-
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61
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33646522422
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Leading references on nonclassical cations: (a) Issue 12 of Acc. Chem. Res. 1983, 16.
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Acc. Chem. Res.
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62
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0004135609
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(with comments by Schleyer, P. v. R.); Plenum: New York
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(b) Brown, H. C. (with comments by Schleyer, P. v. R.) The Nonclassical Ion Problem; Plenum: New York, 1977.
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The Nonclassical Ion Problem
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Brown, H.C.1
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For leading references on proposed nonclassical structures in terpenoid biosynthesis, see: (c) Wessjohann, L. A.; Brandt, W. Chem. Rev. 2003, 103, 1625-1647.
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Chem. Rev.
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Giner, J.-L.1
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68
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For leading references to older proposals by Djerassi, Arigoni, Ruzicka, Eschenmoser, and others, see: (h) Giner, J.-L. Chem. Res. 1993, 93, 1735-1752.
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A thorough review on cyclopropylcarbinyl cations: Olah, G. A.; Reddy, V. P.; Prakash, G. K. S. Chem. Rev. 1992, 92, 69-95.
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Reviews on cation-π interactions include: (a) Ma, J. C.; Dougherty, D. A. Chem. Rev. 1997, 97, 1303-1324.
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Ma, J.C.1
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0033549040
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This reaction can be viewed as an orbital symmetry forbidden all-suprafacial 4-electron (2+2+1) pericyclic reaction (if we think of the reactant as a simple secondary cation we have two C=C π-bonds and an empty p-orbital interacting, but if we think of the reactant as a cyclopropylcarbinyl cation we have a C-C σ-bond, an empty p-orbital, and a C=C π-bond interacting). However, the asynchronicity of bond formation (formation of the five-membered ring leads formation of the four-membered ring) and the relatively long partial C-C bonds in the transition structure suggest that this reaction may actually belong to the class of "apparent violations" of the orbital symmetry rules for which significantly strong overlap of all of the cyclically disposed orbital fragments does not occur at any point along the reaction coordinate. For a related example in a neutral system, see: Kless, A.; Nendel, M.; Wilsey, S.; Houk, K. N. J. Am. Chem. Soc. 1999, 121, 4524-4525
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addition/correction
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(addition/correction: J. Am. Chem. Soc. 1999, 121, 7278).
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(c) Reetz, M. T. Tetrahedron 1973, 29, 2189-2194.
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Tetrahedron
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Reetz, M.T.1
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78
-
-
33646517078
-
-
note
-
(e) For an example of a different sort of dyotropic rearrangement in a carbocationic system, see ref 2e.
-
-
-
-
79
-
-
33646513051
-
-
note
-
12 flattens out in the vicinity of structures resembling 3 and 4, but optimization of the final point on the IRC in each direction leads to 7 and 5, respectively. Thus it seems clear that if any minima that flank the transition structure do exist, the barriers for their conversion to 7 and 5 are very small, at least in the absence of an enzyme active site.
-
-
-
-
80
-
-
84987305333
-
-
The advantage to a cationic transition structure of having a nearby π-system was explored decades ago with CNDO/2 and INDO molecular orbital calculations in the context of very simple models for squalene cyclization. See: Gleiter, R.; Müllen, K. Helv. Chim. Acta 1974, 57, 823-831. This report predates the rise to prominence of cation-π interactions, although electrostatic effects were not discussed explicitly in this early report.
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Helv. Chim. Acta
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Gleiter, R.1
Müllen, K.2
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33646532071
-
-
note
-
6a
-
-
-
-
84
-
-
0023617462
-
-
2) on a bicyclic diene precursor of cation 4 (and therefore, we think, of 7) has also been reported to produce pentalenene (in 38% yield); see: Pattenden. G.; Teague, S. J. Tetrahedron 1987, 43, 5637-5652.
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Tetrahedron
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Pattenden, G.1
Teague, S.J.2
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85
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33646532897
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note
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Two other conformers of 1, differing in the spatial disposition of their isoprene units, are also possible. However, these two conformers (below) are actually enantiomers of 1 and 1′. Although these conformers could, in principle, lead to pentalenene with the absolute stereochemistry shown in Scheme 1, such pathways would not be very direct and are not considered further herein. (Diagram presented)
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86
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0017335378
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Isolation of protoilludene: Nozoe, S.; Robayashi, H.; Urano, S.; Furukawa, J. Tetrahedron Lett. 1977, 16, 1381-1384.
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Tetrahedron Lett.
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Nozoe, S.1
Robayashi, H.2
Urano, S.3
Furukawa, J.4
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87
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0037560988
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Segura, M. J. R.; Jackson, B. E.; Matsuda, S. P. T. Nat. Prod. Rep. 2003, 20, 304-317.
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Nat. Prod. Rep.
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Segura, M.J.R.1
Jackson, B.E.2
Matsuda, S.P.T.3
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89
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0033042413
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(b) Fricke, C.; Hardt, I. H.; König, W. A.; Joulain, D.; Zygadlo, J. A.; Guzman, C. A. J. Nat. Prod. 1999, 62, 694-696.
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Fricke, C.1
Hardt, I.H.2
König, W.A.3
Joulain, D.4
Zygadlo, J.A.5
Guzman, C.A.6
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91
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21244452391
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See, for example: Wendt, K. U. Angew. Chem., Int. Ed. 2005, 44, 3966-3971. Christianson, Cane, and co-workers have referred to such byproducts as "derailment products".
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Angew. Chem., Int. Ed.
, vol.44
, pp. 3966-3971
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Wendt, K.U.1
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92
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33646536987
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See, for example, refs 5, 6
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See, for example, refs 5, 6.
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94
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33646532447
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See also, ref 6
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See also, ref 6.
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95
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17644362311
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For recent examples of this strategy and leading references, see: (a) Vedula, L. S.; Rynkiewics, M. J.; Pyun, H.-J.; Coates, R. M.; Cane, D. E.; Christianson, D. W. Biochemistry 2005, 44, 6153-6163.
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(2005)
Biochemistry
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, pp. 6153-6163
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Vedula, L.S.1
Rynkiewics, M.J.2
Pyun, H.-J.3
Coates, R.M.4
Cane, D.E.5
Christianson, D.W.6
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96
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25444446571
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(b) Vedula, L. S.; Cane, D. E.; Christianson, D. W. Biochemistry 2005, 44, 12719-12727.
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Biochemistry
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Vedula, L.S.1
Cane, D.E.2
Christianson, D.W.3
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97
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0037180538
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(c) Whittington, D. A.; Wise, M. L.; Urbansky, M.; Coates, R. M.; Croteau, R. B.; Christianson, D. W. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 15375-15380. Caution is necessary in such experiments, however; as noted in these reports, the binding conformations of such analogues do not always mirror the productive conformations of cationic intermediates.
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(2002)
Proc. Natl. Acad. Sci. U.S.A.
, vol.99
, pp. 15375-15380
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Whittington, D.A.1
Wise, M.L.2
Urbansky, M.3
Coates, R.M.4
Croteau, R.B.5
Christianson, D.W.6
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98
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The modeling of enzyme-transition structure interactions using quantum mechanical calculations on small models of residues present in enzyme active sites has been referred to as the "theozyme" approach. For leading references, see: (a) Tantillo, D. J.; Chen, J.; Houk, K. N. Curr. Opin. Chem. Biol. 1998, 2, 743-750.
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Curr. Opin. Chem. Biol.
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Tantillo, D.J.1
Chen, J.2
Houk, K.N.3
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Theozymes and catalyst design
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Wiley-VCH: Weinhein, Germany
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(b) Tantillo, D. J.; Houk, K. N. Theozymes and Catalyst Design. In Stimulating Concepts in Chemistry, Wiley-VCH: Weinhein, Germany, 2000; pp 79-88.
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Stimulating Concepts in Chemistry
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Tantillo, D.J.1
Houk, K.N.2
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(c) Na, J.; Houk, K. N.; Shevlin, C. G.; Janda, K. D.; Lerner, R. A. J. Am. Chem. Soc. 1993, 115, 8453-8454.
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Na, J.1
Houk, K.N.2
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Janda, K.D.4
Lerner, R.A.5
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101
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0041411470
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Enzymes, abzymes, chemzymes-theozymes?
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Truhlar, D. G., Morokuma, K., Eds.; ACS Symposium Series 721; American Chemical Society: Washington, DC
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(d) Müller, C.; Wang, L.-H.; Zipse, H. Enzymes, Abzymes, Chemzymes-Theozymes? In Transition State Modeling for Catalysis; Truhlar, D. G., Morokuma, K., Eds.; ACS Symposium Series 721; American Chemical Society: Washington, DC, 1999; pp 61-73.
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, pp. 61-73
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Müller, C.1
Wang, L.-H.2
Zipse, H.3
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