Advances in physical organic chemistry vol 41

Abstraction, hydrogen atom, from O—H bonds, 9, 127Acid–base behaviour macroeycles and other concave structures, 30, 63 Acid–base properties of electronically excited states of organic mo

Editor’s preface

Volume 41-Advances in Physical Organic Chemistry

The capacity for chemists to work and make progress has arguably remained stant through the years However, the scope of the research programs of individualchemists is in general contracting in comparison to the rapidly expanding field ofchemistry At the same time, our work is becoming increasingly focused on makingprogress in well-developed areas of research, and on intractable problems that haveescaped solution over the years All of this has been accompanied by an increase inthe linkage between the seemingly diverse research projects that we study Physicalorganic chemistry suffers when the research of its proponents becomes overly fo-cused and of restricted interest The health of the field requires an awareness of thelinks between research on seemingly unrelated problems, and the fostering of in-teractions between chemists with related interests in structure, kinetics and mech-anism The chapters in this volume represent the great diversity of interests of theirauthors, which range from organic, inorganic and organometallic reaction mech-anisms, to the mechanism for enzyme catalysis This willingness of these authors tocontribute to this monograph reflects well on the breadth of physical organic chem-istry This editor has great admiration for readers with the capacity he lacks of easilygrasping all of the concepts presented in these chapters He does hope that each ofthese chapters has something to offer to all of our readers

con-John P RichardUniversity at Buffalo

ix

Lisa Berreau Department of Chemistry and Biochemistry, Utah State University,

0300 Old Main Hill, Logan, UT 84322-0300, USA

Rudi van Eldik Institut fu¨r Anorganische Chemie, Universita¨t berg, Egerlandstraße 1, D-91058 Erlangen, Germany

Erlangen-Nu¨rn-Nicole Horenstein Department of Chemistry, University of Florida, Gainesville,Florida, 32611-7200, USA

Colin Hubbard Institut fu¨r Anorganische Chemie, Universita¨t berg, Egerlandstraße 1, D-91058 Erlangen, Germany

Erlangen-Nu¨rn-Steve Nelsen Department of Chemistry, University of Wisconsin, Madison,Wisconsin, 53706-1396, USA

Stephen F Schwartz Department of Biophysics and Biochemistry, AlbertEinstein College of Medicine, USA

Ken Westaway Department of Chemistry, Laurentian University, Sudbury,Ontario P3E 2C6, Canada

xi

340, 349Antony, J 116Arca, M 163Arif, A.M 49, 98, 133Arkle, V 14

Armbruster, T 24Arrhenius, S 2Asano, F 38Asano, T 2–3, 23Ashan, M 246Ashwell, M 288, 290, 293Atwood, J.D 5

Aubert, S.D 137Auld, D.S 82Axelsson, B.S 225, 228, 244, 259, 263–264Ayala, L 301

Bain, A.D 284–285, 311Bakac´, A 55

Baker, G.R 61Bakker, M.J 65Bal Reddy, K 63Balny, C 11Banait, N.S 283, 285, 305Banaszczyk, M 134, 137Baron, L.A 102Bartolucci, S 326Barton, J.K 173Basallote, M.G 128Bashkin, J.K 80Basile, L.A 173Basilevsky, M.V 3, 23Basner, J 315Basner, J.E 333, 343Basolo, F 26–27, 45363

Blomgren, F 198, 210Bochicchio, R.C 220, 227Bode, W 102

Boerzel, H 95, 99Boese, W.T 66Bogdanov, B 265Bogin, O 94Bohm, M 276Boiwe, T 92Bolhuis, P 342Bols, M 296, 298–299Bommuswamy, J 285Bonfa, L 144Bonnington, K.J 11Borchardt, R.T 228, 267, 269Borgford, T.J 288, 293Borgis, D 320

Borkovec, M 319–320Boseggia, E 173Botta, M 23Bowen, J.P 300Boxer, S.G 198Boyd, R.J 270Branden, C.-I 92Breslow, R 80, 102, 111, 136, 138, 149Bu¨rgi, H.-B 23–24

Bridgewater, B.M 95–97Brindell, M 14

Brombacher, H 95–97Brooks, C 354–355Brooks, C.L 354Brothers, E.N 116Brower, K.R 12Brown, P 30Brown, R.S 87, 133, 150Brown, T.L 43

Broxterman, Q.B 173Bruice, T.C 328Bruner, M 288–294Brunschwig, B.S 50–51, 186, 198

Bu, W 95, 99Bublitz, G.U 198Buchalova, M 55Buchanan, J.G 307Bucior, I 276

Chou, D.T.H 288, 293Christianson, D.W 83–84, 88, 100Christoph, G.G 55

Chu, F 168, 173Chung, Y.S 137Clark, T 23, 211Clegg, R.M 12Cleland, W.W 134Clennan, E.L 200Clewley, R.G 150Closs, G.L 209Cocho, J.L 87Cohen, D 30Cohen, H 67–68Coleman, J.E 133Concha, N.O 112Connick, R.E 17Connolly, J.A 134Conze, E.G 14Cookson, R.C 30Copeland, K.D 173Corana, F 110–111Cordes, E.H 277, 281Cornelius, R.D 134Corvol, P 129Cotton, S 24Coventry, D.N 11Covey, W.D 43Cowan, D.O 184Coward, J.K 228, 267, 269Cox, J.D 83–84, 88Creutz, C 51, 183, 185–186, 198Cricco, J.A 112

Crich, D 308Crumpton-Bregel, D.M 54Csajka, F 342

Cuesta-Seijo, J.A 124–125, 158Cui, Q 330

Curtis, N.J 87Czapski, G 67–68

Dumas, D.P 137Dunn, M.F 94Dvolaitzky, M 198Dybala-Defratyka, A 220, 222–224,227–229, 250, 262–266, 269–270Dyson, H 354

Ealick, S.E 350Echizen, T 92Eckert, C.A 3Eckert, F 223, 230, 263Edwards, T 128–129Eigen, M 12, 17Eklund, H 92, 95Eldik, R.v 1Elding, L.I 11Elias, H 24, 26, 29, 39–40, 43Elliott, C.M 187

Elmer, T 168, 170Emery, D.C 112Engbersen, J.F.J 111, 163–165, 173Eriksson, J 224, 228, 250, 262, 266, 270Erion, M.D 350

Espenson, J.H 5, 55Evans, D 359Evans, D.W 61Evans, M.G 2Eyring, H 2, 5

Fabiane, S.M 112Fairlie, D.P 119Fang, Y 224, 228, 244, 250, 253, 259,262–264, 266, 270

Fang, Y-R 219, 256–257, 259Farid, S 196–197

Farkas, E 124–125, 158, 160Farrant, G.C 30

Fast, W 112, 116, 122–123Fawcett, J 7

Fa´bia´n, I 23Fedi, V 150–151Fedorov, A 336Fedorov, E 336Fekl, U 49, 52

Garcia-Viloca, M 354–355Garegg, P.J 276, 308Garner, D.K 98Garriga Oostenbrink, M.T 65Gatos, M 144, 173

Ge, Q 111Gelinsky, M 80Gellman, S.H 138Gentile, K.E 194–195, 205, 207George, M.W 15

Gerber, M 94Geremia, S 38Gerhard, A 67Gertner, B.J 325Gibson, Q.H 11Gilchrist, M 107, 110Gillard, R.D 29Gilson, H.S.R 116Giorgi, C 110–111, 150–151, 154, 163Glad, S.S 239

Glasstone, S 2, 5Gobel, M 173Goldanskii, V 321Goldberg, D.P 81, 107–108, 110, 143Goldberg, K.I 49, 52–54

Goldschmidt, Z 30Goldstein, S 67–68Golub, G 68Gomez-Jahn, L 196Gomis-Ruth, F.X 102Gonzalez-Lafont, A 232Goodman, J.L 196Goodwin, H.A 14Gordon, G 5Gorls, H 119Gottlieb, H.E 30Gould, I.R 196–197Grabowski, J 246

He, C 116, 118–121, 123, 155–156, 160Heaton, B.T 5, 18

Hediger, M 134, 137Hedinger, R 26, 44Hegazi, M.F 228, 267, 269Hegetschweiler, K 25–26, 44Hegg, E.L 103–104

Heim, M.H 26Heinemann, F.W 23Heinemann, G 250Heinz, U 112Helm, L 11, 23Hemmingsen, L 116Hendry, P 134, 137Hengge, A.C 134, 137Henkel, G 57Henkelman, G 358–359Hepler, L.G 21Herbst-Irmer, R 124–125, 158Heremans, K 11–12

Hernandez Valladares, M 112Herriott, J.R 102

Herschlag, D 133Herzberg, O 112Hettich, R 134, 137Hiebert, T 286, 305Hikichi, S 91Hill, J.W 244–245, 259Hirota, N 198Hisada, H 143–144, 146Hiyashi, R.K 190Ha¨nggi, P 319–320Hofmann, A 47Holden, H.M 137Holland, A.W 54Holtz, K.M 133Holyer, R.H 17Holz, R.C 128–129Honger, S 350Hopfield, J 316Horenstein, B.A 288–294Horenstein, N.A 275

Jackels, S.C 55Jacobi, A 126Jaenicke, W 201Jansonius, J.N 102Jedrzejas, M.J 133Jeffrey, G.A 91Jencks, W 315Jencks, W.P 107, 110, 121, 248, 277,282–283, 285, 305, 307

Jenner, G 3Jensen, A 26–27, 296Jensen, F 239, 267Jensen, H.H 296, 298–299Jewett, J.G 250

Jiang, N 173Jiang, W 254, 256, 261, 267Jin, H 52

Jitsukawa, K 91Jobe, D.J 265Jockusch, R.A 275, 311Johannesson, G 358–359Johansson, A.A 28Johnson, R.C 198Joly, H.A 247Jones, D.R 134, 137Jonsson, B.H 84, 88Jonsson, H 358–359Jordan, R.B 5Jortner, J 187, 196, 201, 203, 210, 358Jost, A 12

Jubian, V 137Jurek, P 150

Kahn, K 328Kaifer, E 126Kajitani, S 107, 110–111Kamerling, J.P 290Kaminskaia, N.V 116, 119–123, 156, 160Kantrowitz, E.R 133

Kapsabelis, S 163Kaptein, B 173Kardos, J 326Karki, L 198Karlin, K.D 80

Koldziejska-Huben, M 224Kolodziejska-Huben, M 228, 250, 262, 266,270

Komiyama, M 173Kondo, Y 11–12Kong, D 150, 155Konradsson, A.E 195, 200, 207, 211–212Kooijman, H 111, 163–165, 173

Kopf, H 26Kopf-Maier, P 26Koshtariya, D 8Koshy, K.M 246, 261Kosloff, R 185Kotowski, M 5, 8Kou, F 111Koutcher, L 95–97Kovalevsky, A.Y 168Kovari, E 173Kraft, J 11–12Kramer, R 173Krauss, M 116Kraut, J 354Krebs, B 133Krebs, J.F 83Kreevoy, M.M 240Kroemer, R.T 275, 311Kunz, R 356, 358Kupka, T 119Kuroda, Y 87Kuznetzov, A.M 199Kuzuya, A 173

Labinger, J.A 49, 52Lai, Z.-G 234, 255, 257Laidlaw, W.M 198Laidler, K.J 2, 5Lain, L 220, 227Laine, R.M 134, 137Lamzin, V.S 93Lang, E 17Langford, C.H 22Langstrom, B 225, 228, 244, 259, 263–264

Lu, H.P 198

Lu, X.D 277

Lu, Y 162Lucatello, L 173Lucero, C.G 301Luchinat, C 83Ludi, A 23–24Luginbu¨hl, W 24Luiz, M.T.B 128Luo, J 328Luo, Y 211Lutz, S 354Lye, P.G 40Lynch, V 168Lynch, V.M 79, 173Lyngbye, L 296Lynn, K.R 228

Maas, O 25Maccoll, A 243, 251, 263Macholdt, H.-T 43Macleod, N.A 275, 311MacMillar, S 224Madhavan, S 228, 250, 254, 262, 266, 270Magde, D 55

Mahon, M.F 307Makarov, D 321Makowska-Grzyska, M.M 133Makri, N 319

Maltby, D 310Mancin, F 144, 173Mandolini, L 133, 163–164Mangani, S 83, 100Marcus, R.A 184, 201, 203, 318Marder, S.R 198

Marder, T.B 11Mareque-Rivas, J.C 149Maret, W 82

Martell, A.E 128, 150, 155Marti, S 217, 270

Martin, R.B 80Martin-Villacorta, J 116Marx, D 304

Moran, G 30Morishima, I 55Morlok, M.M 89Moro, S 173Moro-oka, Y 91Morris, R.A 232Morris, R.J 93Morrow, J.R 168, 170, 172–173Morse, D.L 63

Mozaki, K 5, 18Mueller, J.L 197Muir, M.M 60Mulbry, W.W 137Mulliken, R.S 186Murphy, P 298Murr, B.L 250

Nakamura, H 211Nakamura, I 107, 110–111Nakata, K 86, 92, 173Nakayama, Y 128–129, 131Namchuk, M.N 295, 297Namuswe, F 143Navon, N 68Nelsen, S.F 183, 186, 188–196, 198–200,203–207, 210–212

Nelson, J.O 137Neubrand, A 57–58Neugebauer, F.A 190–191Neverov, A.A 133Newton, M.D 185, 187, 196–198Nu´n˜ez, S 315, 335–336, 340–341, 349Nguyen, T 289

Paoletti, P 110–111, 150–151Paoli, P 110–111

Paris, G 289Parish, L 11Park, D.-H 92Park, J 184Parker, A.W 15Parkin, G 80–81, 89, 95–97Parshall, G.W 66

Parsons, S.A 27Paschkewitz, J.S 232Pauling, L 220, 315Paulson, J.F 232Paulus, H 24, 26, 29, 39Pauptit, R.A 102Pavan Kumar, P.N.V 38Payne, D.J 112

Pearson, R.G 45, 60Pelizet, G 38Pelmenschikov, V 102Pelzer, H 2

Peng, W 173Periana, R.A 52Perra, A 163Perrin, M.W 2–3Persson, J 228, 244, 253, 259, 263–264Petsko, G 129, 326

Petter, R 138Pettersson, L.G.M 23Pfeffer, M 60Pham, T.V 232, 242–243, 245–246, 253,259–261

Phelps, D.K 199Phillips, D.D 304Pierattelli, R 83Pinnick, H.R 246Piotrowiak, P 199Pipoh, R 57Pittet, P.-A 23–24Pitts, J.N 197Pladziewicz, J.R 203Plapp, B.V 92, 95Pliego, J.R 266Pocker, Y 107Poe, A.J 58Poirel, L 112Poirier, R.A 234–238, 247

Romero, J.A.C 301Romesberg, F 317, 326Rossi, P 173

Rossolini, G.M 112Rostkowaski, M 227–229, 263, 269Rostkowski, M 220, 222–224, 264–265Rotzinger, F.P 23

Roughton, F.J.W 10–11Rozenfeld, R 129Rubin, E 103Rubinowicz, A 197Rudzinski, J 254Ruf, M 89, 95–97, 104, 107Ruggiero, D.G 270Ruggiero, G.D 307Rulisek, L 94Runser, C 198Russell, D.R 7Rutsch, R 126Ryabov, A.D 60Ryba, D.W 66Ryberg, P 228, 250, 262, 266, 270

Safford, L.K 51Sagi, I 94Sakaki, S 51Sakiyama, H 128–129, 131, 133Saldana, J.L 11

Salignac, B 26, 44Salter, M.H 81, 107–108, 110Salvio, R 133, 163–164Sandlers, Y 310

Shionoya, M 80, 94–95, 107, 110–111Shiota, T 84, 107

Shiro, M 84, 86, 92, 107, 110–111, 135, 137,

139, 146–147Showalter, B.M 307Shul’pin, G.B 49Sidorenkova, E 25Sidorenkova, H 23Siegbahn, P.E.M 102Siegfried, V 26Silverman, D.N 83, 86Simons, J.P 311Sims, L.B 220Singh, S 111, 138Singleton, J 200Sinnott, M.L 282, 284–285, 288, 290, 293Sisley, M.J 17, 67

Sissi, C 173Skowronski, E 299, 308Sladkov, A.M 28Slebocka-Tilk, H 87, 150Sligar, S 357

Smith, A.E 43Smith, H 350Smith, J 79, 173Smith, K 83–84Smith, P.J 255Smythe, N.A 53–54Snauwaert, J 11Snoek, L.C 275, 311Soderberg, B.O 92Soderlund, G 92Sohi, M.K 112Somsak, L 276Sordo, T.L 116Soto, R.P 112Spek, A.L 45, 111, 163–165, 173Spencer, J 112

Spey, S.E 11

Tabacco, S.A 301Tabata, Y 15Tabushi, I 87Tada, T 143–144, 146Tafesse, F 137Takabayashi, K 350Takamura, M 107, 110, 113, 115–116, 124Takasaki, B 137

Takasaki, B.K 103Talbot, F.O 311Talkner, P 319–320Tanabe, H 228, 246Tanaka, K.S.E 276, 279Tanaka, M 11, 17, 91Tang, W 111Tapia, O 92Tarani, M 173Tate, A 138Taube, D.J 52, 55Taube, H 52, 183Taube, H.J 5–6, 18Tauzher, G 38Taylor, I.A 112Taylor, J.W 219, 261Tecilla, P 144, 173Tei, L 163Teki, Y 195, 200, 206–207, 212Telo, J.P 211

Templeton, J.L 52Thaler, F 23Thompson-Colo´n, J.A 188, 190Thorpe, I 354–355

Tobe, M.L 5, 27Tokairin, I 91Toleman, M.A 112Tomasi, J 223, 230, 263Tomic, M 250

Tone, K 133Tonellato, U 144, 173Toniolo, C 173Topaler, M 319Torre, A 220, 227Tosacano, J.P 307Toteva, M.M 278–279, 281, 287Towrie, M 15

van der Graaf, T 65

van der Zwan, G 325

Vidovic, D 124–125, 158, 160Viggiano, A.A 232

Vila, A.J 112, 116Vitullo, V.P 246Vliegenthart, J.F.G 290Voelkel, G 17

Vogler, R 80Vontor, T 292

Wagner, S 350Wahlgren, U 23Wahnon, D 137Waissbluth, M.D 12Wakita, Y 91Waldbach, T.A 59Wales, D 359Wall, M 137Walsh, T.R 112Walters, K.A 198Walz, R 96–97Walz, W 98Wan, T 112Wanat, A 14Wang, L.J 309Wang, M 173Wang, S.L.B 57Wang, X 162Wang, Y 188, 190, 234–238Wang, Z 112, 116, 122–123Warburton, P.M 55Wasden, C.W 133Waszczylo, Z 246, 255, 257Watson, J.N 288, 293Watts, A.G 289Weaver, M.J 51, 199Weaver, M.N 211Webb, S.P 92Weber, J 23, 25Weber, W 14Wehenkel, A 289Wehnert, A 83, 88Weinan, E 359Weinberg, N 270Weinberg, W 358Weis, K 96–97, 104, 107, 140

Wu, Z 299, 308Wulff, W.D 57Wynne-Jones, W.F.K 2

Xia, C 173Xia, J 111Xiang, Q 173Xie, R 173

Xu, Y 111Xue, Y 84, 88

Yamada, Y 94–95Yamaguchi, S 91Yamataka, H 228, 246, 267Yang, D 111

Yang, J 15, 289Yang, J.S 289–290Yang, M.Y 168, 172Yang, X 162Yanigada, S 50Yankwich, P.E 228Yankwich, P.F 228Yano, Y 17Yashiro, M 173Yeagley, D 296, 300Yerly, F 23

Yin, X 111Yohoyama, T 155Yoshikawa, Y 143–144, 146Youg, R.H 196

Young, G 277Young, R.H 197

Zhu, J 286–287, 305Zhu, S 110–111Zhu, Y 162Ziller, J.W 301Zimmer, L.L 55Zink, J.I 211Zou, X 137Zsolnai, L 126Zwanzig, R 320

2-hydroxypropyl 4-nitrophenyl phosphate

chromium and tungsten pentacarbonyl

compounds, cycloaddition reactions, 57

metal pentacarbonyl a, b-unsaturated

Fischer carbene complexes, addition

reactions, 57–58

osmium cluster, addition to, 58–59

Adenosylcobalamin (AdoCbl), 31

Aeromonas proteolytica (ApAP), 128

co-catalytic zinc centers in, 128f

peptide hydrolysis by, mechanistic

path-way for, 129f

Alcohol oxidation, in Zn–OHn(n=1 or 2)

species reactivity 92–100

[(ebnpa)Zn––OCH3]ClO4and

[(ebnpa)Z-n–OH]ClO4, preparative routes for, 99f

deprotonation of the zinc alcohol

com-plexes, 95, 96f

horse liver alcohol dehydrogenase, 93f

macrocyclic zinc complex, hydride

trans-fer catalyzed by, 94f

reaction with trifluoroethanol, 98f

structure/reactivity relationships, 95

tetrahedral zinc-alkoxide and aryloxide

complexes, equilibrium formation, 97

zinc alkoxide complexes, hydride transfer

geometrical changes at the zinc centerduring, 106

metal center role in, 104fmetal-mediated, 103mononuclear zinc complexes, reactionsinvolving, 100–106

peptide hydrolysis, 128–133, see alsoindividual entry

phosphate ester hydrolysis, 133–173, seealso individual entry

zinc-mediated, 105b-Lactam hydrolysis, 111–127, see alsoindividual entry

Aryl-bridged ligands, 136

B.Cereus, 113f

B fragilis, 113f, 116, 122, 124

B stearothermophilus, 326Benderskii’s model, 321–326Bigeleisen treatment, 218Bimido ligand, 170fbis(1-methylimidazol-2-ylmethyl)ethyla-mine, 151f

bis(4-nitrophenyl) phosphate hydrolysis,150f, 153f–154, 157, 159f

Bixon–Jortner (BJ) approach, 196Bizinc cryptand complex, 135fBond Strength Hypothesis, 244, 247,253–257

BPAN (2, methyl]-1,8-naphthyridine ligand, 155s- and p-Bridged dinitrogen-centered inter-valence radical cations, electron transferreactions within, 183–212, see also underelectron transfer (ET) reactions

7-bis[2-(2-pyridylethyl)amino-393

4-s-bond-bridged IV compounds in

acet-onitrile, 190t

4-s-bondbridged bis(hydrazine) IV

radi-cal cations, ESR rate constants for,

192t

6-s-bondbridged bis(diazenium) IV

radi-cal cations, ESR rate constants for,

Carbonic anhydrases (CAs), 83

active site features, 83f

a-type CA, catalytic mechanism, 84f

Carboxy ester hydrolysis reactivity of

mononuclear zinc complexes, 107–111,

see also 4-Nitrophenyl acetate hydrolysis

sodium salt of, 119f

Chelate tetradentate tripodal ligands, 147

Chromium and tungsten pentacarbonyl

compounds, cycloaddition reactions, 57

cis-2,4,6-traminocyclohexane-1,3,5-triol-containing ligands, 159f, 160

CO2hydration, 83–92, see also Carbonic

anhydrases (CAs)

bridging bicarbonate complexes, 91f

catalytic reactivity, mechanism, 87

catalyzed by [([12]aneN3)Zn(OH)]+, 85f

mononuclear tetrahedral zinc hydroxide

and aqua complexes, 90f

supporting chelate ligands for, 88

136, 160, 163, 200–202, 224Dinuclear pallada- and platina-cycles,monomerisation, 60–62

ebnpa-Ligated zinc methoxide and xide complexes, 99

hydro-methanolysis equilibrium of, 100fEigen–Wilkins mechanism, 17, 29Electron transfer (ET) reactions, 183–212,see also under s- and p-bridged dinitro-gen-centered intervalence radical cations

11 conformers, preparation, 190–192

18 linked bonds, interconversion of stereomeric conformations, 194f9,10–anthracene-bridge compound 28+,195

dia-aryl-bridged bis(hydrazine) IV radicalcations, ESR rate constants for, 195tbis(hydrazine) radical cations in, 201f

BJ treatment for ET within IV pounds, 208–211

com-Class I compounds, 183Class II compounds, 183Class II IV compound, Marcus–Hushclassical two-state model, 184f, 185fClass II IV compounds, 184

Class III compounds, 183Class III IV compound, 184Creutz–Taube complex, Class IV, 183

ET distance estimation, 197–198hydrazines, ET reactions in, 188

IV band, determination of ET parametersfrom, 196–198

IV bandwidth, 196–197low-bridge-oxidized excitation energies,effecting, 211–212

neutral forms of Hy2Ar+studied for, 194fsolvent effects in, 201

Enzymatic systems, rate-promoting motions

in, 328–342

SUBJECT INDEX394

basin hopping in the conformation space,

357–358

conformation space, searching, 356–359

conformational fluctuations, 353–359

correlated protein motions, 342–353,

see also under protein motions

horse liver alcohol dehydrogenase

(HLADH), 328–330

human purine nucleoside phosphorylase

(hPNP), 335–342, see also separate

enzymatic systems, rate-promoting

mo-tions in, 328–342, see also separate entry

proton transfer and rate-promoting

vi-brations, 317–328, see also separate

entry

Enzyme lactate dehydrogenase (LDH),

316

Essential dynamics (ED), 347–353

Fermi’s golden rule, 321

Hydrotris(pyrazolyl)borate-ligated zinccomplexes, 98

Imidazole (CN(Im)Cbl), 36, 37fImidazole/carboxylate-donor ligand, 170fInfrared (IR) spectroscopy, 8

Ion-pairing effects, 198–200Isomerisation reactions, 49–50

Kinetic isotope effects (KIEs), 217–270,see also under SN2 reactions

incoming group KIEs, 225leaving group KIEs, 219–225primary KIE, 219–230secondary KIEs, 230–251secondary a-deuterium KIEs, 230–249secondary b-deuterium KIEs, 249–251substituents, the solvent, ion pairing andenzymes effect determination using,251–270, see also individual entrytheory, 217–251

L24 ligand framework, 151L25–L27 ligands, 155fL28–L30 ligands, 156fL33 ligand, 162fL34 ligand, 163, 165fL35 ligand, 163, 165fL38–L40 ligands, 171fL41 and L42 ligands, 172fLactate dehydrogenase (LDH), 330–335binding site of, 331f

reactive trajectories in, 343–344b-Lactam hydrolysis, 111–127[([12]aneN4)Zn–OH]+with penicillin G,116f

[(TpAr,Me)Zn–OH] with, 115f[(TpPh,Me)Zn–OH] reactivity with deriva-tives of penicillin and cephalosporin,114f

[(TpPh,Me)Zn–OH] reactivity with activated b-lactams, 114f

un-[Zn2L3(m-OH) (NO3)2] formation in

Metal pentacarbonyl a, b-unsaturated

Fischer carbene complexes, addition

O2PPh2)](ClO4)2,118fcatalyzed by [Zn2L3(m-OH)-(NO3)2] ver-sus [Zn2L3(m-OD)(NO3)2], 121–122pH-dependence of, 119f

N-p-nitrophenyl- L-leucine, 131fNuclear magnetic resonance (NMR) spec-troscopy, 8, 16–18

wide bore probe head for HPNMR, 19fOBISDIEN chelate ligand, 130f

Organometallic reactions, activation lumes for, interpretation and mechanisticsignificance, 1–69

vo-basic principles and theory, 1–5conventional time-range reactions, 6–10experimental, 5–22

general considerations, 5–6mixing methods, 10–12partial molar volumes from density mea-surements, 18

radiation-induced reactions, 12–16,see also separate entry

range of values and correlation of DV#

with DS#, 18–21rapid reactions, 10–12relaxation methods, 12safety considerations, 21–22thermal organometallic reactions, vo-lumes of activation for, 22–63 see alsoseparate entry

thermodynamic functions in, 1–3Osmium cluster, addition to, 58–59Oxazetidinylacetate adducts, 126fOxidative addition and reductive elimina-tion reactions, 52–55

P diminuta, 137Penicillins, 112fPenicillin G, 121, 125peptide hydrolysis, 128–133Gly–Gly hydrolysis, 130fPhenanthroline-containing polyaminemacrocyclic ligand, 132f

Phosphate ester hydrolysis, 133–173[(tapa)Zn(H2O)]2+and [(tapa)Zn(H2O)]2+, 149f

alkaline phosphatase catalysing, 134f

SUBJECT INDEX396

bis(4-nitrophenyl) phosphate, 140

bis(4-nitrophenyl)phosphate catalyzed

hydrolysis, 164f

by bizinc crypt and complex, 135f

dianionic ICIMP and trianionic BCIMP

ligands, 162f

Htdmbpo and Hbdmbbppo ligands, 169f

involving an internal alkoxide

nucleo-phile, reaction pathway, 141f

macrocyclic and linear polyamine ligands,

145f

phosphate diester and triester hydrolysis,

137–173

phosphate monoester hydrolysis, 133–137

phosphate triester hydrolysis reactivity of

[(TpR,Me)Zn–OH] compounds, 142f

tris(4-nitrophenyl) phosphate reaction,

143f

tris(pyrazolyl)borate-ligated zinc

hydro-xide complexes, 140

p-Nitrobenzaldehyde, 94

Polyamine macrocyclic ligand, 132f

Protein motions, correlated, 342–353

atomic description of relevant catalytic

motions, 344–347

concerted vs stepwise transfers, 346

donor–acceptor axis and compression

reaction coordinate, 346–347

essential dynamics (ED), 347–353

experimental site-directed mutagenesis,

352–353

mobile residues in the active site, 350–352

substrate binding in PNP, 349–350

transition path sampling (TPS), 342–347

Proteins, dynamic and statistical

promoting vibration and dephasing, 327

promoting vibration and turnover rate,

rate-promoting vibrations, 320–325vibrations in condensed phase, theory ofpromoting, 322–325

Pulse-radiolysis-induced reactions, 66–69Pyrazolate-based chelate ligands, 158binuclear zinc complex of, 161f

Pyridinium triflate, 122

Radiation-induced organometallic tions, volumes of activation for, 63–69carbon monoxide activation, 65photo-induced homolysis reactions, 65photo-induced reactions, 63–66pulse-radiolysis-induced reactions,66–69

reac-radiation-induced reactions, 12–16electrochemical methods, 16high pressure electrochemical cell, 17fphoto-induced methods, 12–15pulse radiolysis, 15–16volumes of activation for, 63–69, see alsoindividual entry

Redox reactions, 50–52

S-adenosylmethionine, 268fShilov-type system, 49S-methyldibenzothiophenium ion, 268f

SN2 reactions, transition states structuredetermination, using kinetic isotope ef-fects, 217–270, see also kinetic isotopeeffects (KIEs)

enzyme catalysis effect on, 267–270isotopically labeled atom transfer, intransition state, 225–230

solvation rule for, 266solvation rule for, 266substituents, the solvent, ion pairing andenzymes effect in, 251–270

theory and experimental results to model,262–267

a-carbon KIEs measured for, 228t

Solvolysis, 27

Stenotrophomanas maltophilia, 113f

Stopped-flow (s.f.) methods, to kinetic

studies, 11

high pressure s.f unit, 13f, 14f

Substituents, the solvent, ion pairing and

enzymes effect determination using KIEs,

251–270

changes at the a-carbon, 257–260

changing the leaving group, 251–254

changing the nucleophile, 254–255

effect of ion pairing of the nucleophile,

for arene–osmium compounds, 24

for dihydrogen–amine complexes of

radiation-induced organometallic

reac-tions, volumes of activation for, 63–69,

see also individual entry

reactions of small molecules, 55–57redox reactions, 50–52

solvent exchange, 23–26Thermoanaerobacter brockii, 94Thermolysin, 102

Time-Resolved Infrared (TRIR) scopy, 15

spectro-Transition path sampling (TPS), 317,342–347

Transition state theory (TST), 316Triazacyclononane-containing ligands, 170Tripodal tetradentate ligands, 147f, 148fUnrestricted Hartee-Fock (UHF) calcula-tion, 191

UV/visible spectrophotometry, 8Zero-point energy (ZPE) factors, in SN2reactions, 218, 226, 230, 232

Zinc-containing metalloenzymes, 79–173,see also under Zn–OHn(n=1 or 2) speciesZn–OHn(n=1 or 2) species reactivity,kinetic and mechanistic studies, 79–173alcohol oxidation, 92–100, see also indivi-dual entry

amide hydrolysis, 100–133, see also dividual entry

in-CO2hydration, 83–92, see also individualentry

divalent zinc and Zn–OHnspecies, erties, 80–81

prop-four-coordinate Zn(II)–OH2complexes,81f

N4- and N3O-ligated Zn–OH2complexes,82

Zinc aqua (Zn–OH2) species, 80Zn(II) in catalysis, roles for, 81–82Zwanzig Hamiltonian equation, 320, 323

SUBJECT INDEX398

de Gunst, G.P., 11, 225

de Jong, F., 17, 279Denham, H., 31, 249Desvergne, J.P., 15, 63Detty, M.R., 39, 79Dosunmu, M.I., 21, 37Drechsler, U., 37, 315Eberson, K., 12, 1; 18, 79;

31, 91Eberson, U., 36, 59Ekland, J.C., 32, 1Eldik, R.V., 41, 1Emsley, J., 26, 255Engdahl, C., 19, 223Farnum, D.G., 11 123Fendler, E.J., 8, 271Fendler, J.H., 8, 271; 13, 279Ferguson, G., 1.203

Fields, E.K., 6, 1Fife, T.H., 11, 1Fleischmann, M., 10, 155Frey, H.M., 4, 147Fujio, M., 32, 267Gale, P.A., 31, 1Gao, J., 38, 161Garcia-Viloca, M., 38, 161Gilbert, B.C., 5, 53Gillespie, R.J., 9, 1Gold, V., 7, 259Goodin, J.W., 20, 191Gould, I.R., 20, 1Greenwood, H.H., 4, 73Gritsan, N.P., 36, 255Hamilton, T.D., 40, 109Hammerich, O., 20, 55

Harvey N.G., 28, 45Hasegawa, M., 30, 117Havjnga, E., 11, 225Henderson, R.A., 23, 1Henderson, S., 23, 1Hengge, A.C., 40, 49Hibbert, F., 22, 113; 26, 255Hine, J., 15, 1

Hogen-Esch, T.E., 15, 153Hogeveen, H., 10, 29, 129Horenstein, N.A., 41, 277Hubbard, C.D., 41, 1Huber W., 28, 1Ireland, J.F., 12, 131Iwamura, H., 26, 179Johnson, S.L., 5, 237Johnstone, R.A.W., 8, 151Jonsa¨ll, G., 19, 223Jose´, S.M., 21, 197Kemp, G., 20, 191Kice, J.L., 17, 65Kirby, A.J., 17, 183; 29, 87Kitagawa, T., 30, 173Kluger, R.H., 25, 99Kochi, J.K., 29, 185; 35, 193Kohnstam, G., 5, 121Korolev, V.A., 30, 1Korth, H.-G., 26, 131Kramer, G.M., 11, 177Kreevoy, M.M., 6, 63; 16, 87Kunitake, T., 17, 435Kurtz, H.A., 29, 273

Le Fe`vre, R.J.W., 3, 1Ledwith, A., 13, 155Lee, I., 27, 57Lee, J.K., 38, 183Liler, M., 11, 267Lin, S.-S., 35, 67Lodder, G., 37, 1Logan, M.E., 39, 79Long, F.A., 1, 1Lu¨ning, U., 30, 63Maccoll, A., 3, 91381

Riveros, J.M., 21, 197Robertson, J.M., 1, 203Romesberg, F.E., 39, 27Rose, P.L., 28, 45Rosenberg, M.G., 40, 1Rosenthal, S.N., 13, 279Rotello, V.M., 37, 3l5Ruasse, M.-F., 28, 207Russell, G.A., 23, 271Saettel, N.j., 38, 87Samuel, D., 3, 123Sanchez, M de N de M., 21,37

Sandstro¨m, J., 25, 1Save´ant, J.-M., 26, 1; 35, 117Savelli, G., 22, 213

Schaleger, L.L., 1, 1Scheraga, H.A., 6, 103Schleyer, P., von R., 14, 1Schmidt, S.P., 18, 187Schowen, R.L., 39, 27Schuster, G.B., 18, 187; 22,311

Schwartz, S D., 41, 317Scorrano, G., 13, 83Shatenshtein, A.I., 1, 156Shine, H.J., 13, 155Shinkai, S., 17 435Siehl H.-U., 23, 63Silver, B.L., 3, 123Simonyi, M., 9, 127Sinnott, M.L., 24, 113Speranza, M., 39, 147Stock, L.M., 1, 35Strassner, T., 38, 131Sugawara, T., 32, 219Sustmann, R., 26 131Symons, M.C.R., 1, 284Takashima, K., 21, 197Takasu, I., 32, 219Takeuchi, K., 30, 173Tanaka, K.S.E., 37, 239

Tantillo, D.J., 38, 183Ta-Shma, R., 27, 239Tedder, J.M., 16, 51Tee, O.S., 29, 1Thatcher, G.R.J., 25, 99Thomas, A., 8, 1Thomas, J.M., 15, 63Tidwell T.T., 36, 1Tonellato, U., 9 185Toteva, M.M., 35, 67; 39, 1Toullec, J., 18, 1

Tsuji, Y., 35, 67; 39, 1Tsuno, Y., 32, 267Tu¨do¨s, F., 9, 127Turner, D.W., 4, 31Turro, N.J., 20, 1Ugi, I., 9, 25Walton, J.C., 16, 51Ward, B., 8, 1Warshel, A., 40, 201Watt, C.I.F., 24, 57Wayner, D.D.M., 36, 85Wentworth, P., 31, 249Westaway, K.C., 31, 143; 41,219

Westheimer, F.H., 21, 1Whalen, D.L., 40, 247Whalley, E., 2, 93Wiest, O., 38, 87Williams, A., 27, 1Williams, D.L.H., 19, 381Williams, J.M., Jr., 6, 63Williams, J.O., 16, 159Williams, K.B., 35, 67Williams, R.V., 29, 273Williamson, D.G., 1, 365Wilson, H., 14, 133Wolf, A.P., 2, 201Wolff, J.J., 32, 121Workentin, M.S, 36, 85Wortmaan, R., 32, 121Wyatt, P.A.H., 12, 131Zimmt, M.B., 20, 1Zipse, H., 38, 111Zollinger, H., 2, 163Zuman, P., 5, 1CUMULATIVE INDEX OF AUTHORS382

Abstraction, hydrogen atom, from O—H bonds, 9, 127

Acid–base behaviour macroeycles and other concave structures, 30, 63

Acid–base properties of electronically excited states of organic molecules, 12, 131

Acid solutions, strong, spectroscopic observation of alkylcarbonium ions in, 4, 305Acids, reactions of aliphatic diazo compounds with, 5, 331

Acids, strong aqueous, protonation and solvation in, 13, 83

Acids and bases, oxygen and nitrogen in aqueous solution, mechanisms of proton transferbetween, 22, 113

Activation, entropies of, and mechanisms of reactions in solution, 1, 1

Activation, heat capacities of, and their uses in mechanistic studies, 5, 121

Activation, volumes of, use for determining reaction mechanisms, 2, 93

Addition reactions, gas-phase radical directive effects in, 16, 51

Aliphatic diazo compounds, reactions with acids, 5, 331

Alkene oxidation reactions by metal-oxo compounds, 38, 131

Alkyl and analogous groups, static and dynamic stereochemistry of, 25, 1

Alkylcarbonium ions, spectroscopic observation in strong acid solutions, 4, 305

Ambident conjugated systems, alternative protonation sites in, 11, 267

Ammonia liquid, isotope exchange reactions of organic compounds in, 1, S56

Anions, organic, gas-phase reactions of, 24, 1

Antibiotics, b-lactam, the mechanisms of reactions of, 23, 165

Aqueous mixtures, kinetics of organic reactions in water and, 14, 203

Aromatic photosubstitution, nucleophilic, 11, 225

Aromatic substitution, a quantitative treatment of directive effects in, 1, 35

Aromatic substitution reactions, hydrogen isotope effects in, 2, 163

Aromatic systems, planar and non-planar, 1, 203

N-Arylnitrenium ions, 36, 167

Aryl halides and related compounds, photochemistry of, 20, 191

Arynes, mechanisms of formation and reactions at high temperatures, 6, 1

A-SE2 reactions, developments In the study of, 6, 63

Base catalysis, general, of ester hydrolysis and related reactions, 5, 237

Basicity of unsaturated compounds, 4, 195

Bimolecular substitution reactions in protic and dipolar aprotic solvents, 5, 173

Carbanion reactions, ion-pairing effects in, 15,153

Carbene chemistry, structure and mechanism in, 7, 163

Carbenes generated within cyclodextrins and zeolites, 40, 1

383

Carbenes having aryl substituents, structure and reactivity of, 22, 311

Carbocation rearrangements, degenerate, 19, 223

Carbocationic systems, the Yukawa–Tsuno relationship in, 32, 267

Carbocations, partitioning between addition of nucleophiles and deprotonation, 35, 67Carbocations, thermodynamic stabilities of, 37, 57

Carbon atoms, energetic, reactions with organic compounds, 3, 201

Carbon monoxide, reactivity of carbonium ions towards, 10, 29

Carbonium ions, gaseous, from the decay of tritiated molecules, 8, 79

Carbonium ions, photochemistry of, 10, 129

Carbonium ions, reactivity towards carbon monoxide, 10, 29

Carbonium ions (alkyl), spectroscopic observation in strong acid solutions, 4, 305

Carbonyl compounds, reversible hydration of, 4, 1

Carbonyl compounds, simple, enolisation and related reactions of, 18, 1

Carboxylic acids, tetrahedral intermediates derived from, spectroscopic detection andinvestigation of their properties, 21, 37

Catalysis, by micelles, membranes and other aqueous aggregates as models of enzyme action,

17, 435

Catalysis, enzymatic, physical organic model systems and the problem of, 11, 1

Catalysis, general base and nucleophilic, of ester hydrolysis and related reactions, 5, 237Catalysis, micellar, in organic reactions; kinetic and mechanistic implications, 8, 271Catalysis, phase-transfer by quaternary ammonium salts, 15, 267

Catalytic antibodies, 31, 249

Cation radicals, in solution, formation, properties and reactions of, 13, 155

Cation radicals, organic, in solution, and mechanisms of reactions of, 20, 55

Cations, vinyl, 9, 135

Chain molecules, intramolecular reactions of, 22, 1

Chain processes, free radical, in aliphatic systems involving an electron transfer reaction, 23,271

Charge density-NMR chemical shift correlation in organic ions, 11, 125

Charge distribution and charge separation in radical rearrangement reactions, 38, 111Chemically induced dynamic nuclear spin polarization and its applications, 10, 53

Chemiluminesance of organic compounds, 18, 187

Chiral clusters in the gas phase, 39, 147

Chirality and molecular recognition in monolayers at the air–water interface,

28, 45

CIDNP and its applications, 10, 53

Computer modeling of enzyme catalysis and its relationship to concepts in physical organicchemistry, 40, 201

Computational studies of alkene oxidation reactions by metal-oxo compounds, 38, 131Computational studies on the mechanism of orotidine monophosphate decarboxylase,

38, 183

Conduction, electrical, in organic solids, 16, 159

Configuration mixing model: a general approach to organic reactivity, 21, 99

Conformations of polypeptides, calculations of, 6, 103

Conjugated molecules, reactivity indices, in, 4, 73

Cross-interaction constants and transition-state structure in solution, 27, 57

Crown-ether complexes, stability and reactivity of, 17, 279

Crystalographic approaches to transition state structures, 29, 87

Cyclodextrins and other catalysts, the stabilisation of transition states by, 29, 1

CUMULATIVE INDEX OF TITLES384

D2O—H2O mixtures, protolytic processes in, 7, 259

Degenerate carbocation rearrangements, 19, 223

Deuterium kinetic isotope effects, secondary, and transition state structure, 31, 143

Diazo compounds, aliphatic, reactions with acids, 5, 331

Diffusion control and pre-association in nitrosation, nitration, and halogenation, 16, 1Dimethyl sulphoxide, physical organic chemistry of reactions, in, 14, 133

Diolefin crystals, photodimerization and photopolymerization of, 30, 117

Dipolar aptotic and protic solvents, rates of bimolecular substitution reactions in, 5, 173Directive effects, in aromatic substitution, a quantitative treatment of, 1, 35

Directive effects, in gas-phase radical addition reactions, 16, 51

Discovery of mechanisms of enzyme action 1947–1963, 21, 1

Displacement reactions, gas-phase nucleophilic, 21, 197

Donor/acceptor organizations, 35, 193

Double bonds, carbon–carbon, electrophilic bromination of: structure, solvent and

mechanism, 28, 171

Dynamics for the reactions of ion pair intermediates of solvolysis, 39, 1

Effect of enzyme dynamics on catalytic activity, 41, 317

Effective charge and transition-state structure in solution, 27, 1

Effective molarities of intramolecular reactions, 17, 183

Electrical conduction in organic solids, 16, 159

Electrochemical methods, study of reactive intermediates by, 19, 131

Electrochemical recognition of charged and neutral guest species by redox-active receptormolecules, 31, 1

Electrochemistry, organic, structure and mechanism in, 12, 1

Electrode processes, physical parameters for the control of, 10, 155

Electron donor–acceptor complexes, electron transfer in the thermal and photochemicalactivation of, in organic and organometallic reactions 29, 185

Electron spin resonance, identification of organic free radicals, 1, 284

Electron spin resonance, studies of short-lived organic radicals, 5, 23

Electron storage and transfer in organic redox systems with multiple electrophores, 28, 1Electron transfer, 35, 117

Electron transfer, in thermal and photochemical activation of electron donor-acceptorcomplexes in organic and organometallic reactions, 29, 185

Electron transfer, long range and orbital interactions, 38, 1

Electron transfer reactions within s- and p-bridged nitrogen-centered intervalence radicalions, 41, 185

Electron-transfer, single, and nucleophilic substitution, 26, 1

Electron-transfer, spin trapping and, 31, 91

Electron-transfer paradigm for organic reactivity, 35,193

Electron-transfer reaction, free radical chain processes in aliphatic systems involving an, 23,271

Electron-transfer reactions, in organic chemistry, 18, 79

Electronically excited molecules, structure of, 1, 365

Electronically excited states of organic molecules, acid-base properties of, 12, 131

Energetic tritium and carbon atoms, reactions of, with organic compounds, 2, 201

Enolisation of simple carbonyl compounds and related reactions, 18, 1

Entropies of activation and mechanisms of reactions in solution, 1, 1

Enzymatic catalysis, physical organic model systems and the problem of, 11, 1

Enzyme action, catalysis of micelles, membranes and other aqueous aggregates as models of,

17, 435

Enzyme action, discovery of the mechanisms of, 1947–1963, 21, 1

Equilibrating systems, isotope effects in NMR spectra of, 23, 63

Equilibrium constants, NMR measurements of, as a function of temperature, 3, 187Ester hydrolysis, general base and nucleophitic catalysis, 5, 237

Ester hydrolysis, neighbouring group participation by carbonyl groups in, 28, 171

Excess acidities, 35, 1

Exchange reactions, hydrogen isotope, of organic compounds in liquid ammonia, 1, 156Exchange reactions, oxygen isotope, of organic compounds, 2, 123

Excited complexes, chemistry of, 19, 1

Excited molecular, structure of electronically, 3, 365

Finite molecular assemblies in the organic solid state: toward engineering properties of solids,

40, 109

Fischer carbene complexes, 37, 137

Force-field methods, calculation of molecular structure and energy by, 13, 1

Free radical chain processes in aliphatic systems involving an electron-transfer reaction, 23,271

Free Radicals 1900–2000, The Gomberg Century, 36, 1

Free radicals, and their reactions at low temperature using a rotating cryostat, study of, 8, 1Free radicals, identification by electron spin resonance, 1, 284

Gas-phase heterolysis, 3, 91

Gas-phase nucleophilic displacement reactions, 21, 197

Gas-phase pyrolysis of small-ring hydrocarbons, 4, 147

Gas-phase reactions of organic anions, 24, 1

Gaseous carbonium ions from the decay of tritiated molecules, 8, 79

General base and nucleophilic catalysis of ester hydrolysis and related reactions, 5, 237The Gomberg Century: Free Radicals 1900–2000, 36, 1

Gomberg and the Nobel Prize 36, 59

H2O—D2O mixtures, protolytic processes in, 7, 259

Halides, aryl, and related compounds, photochemistry of, 20, 191

Halogenation, nitrosation, and nitration, diffusion control and pre-association in, 16, 1Heat capacities of activation and their uses in mechanistic studies, 5, 121

Heterolysis, gas-phase, 3, 91

High-spin organic molecules and spin alignment in organic molecular assemblies, 26, 179Homoaromaticity, 29, 273

How does structure determine organic reactivity, 35, 67

Hydrated electrons, reactions of, with organic compounds, 7, 115

Hydration, reversible, of carbonyl compounds, 4, 1

Hydride shifts and transfers, 24, 57

Hydrocarbon radical cations, structure and reactivity of, 38, 87

Hydrocarbons, small-ring, gas-phase pyrolysis of, 4, 147

Hydrogen atom abstraction from 0—H bonds, 9, 127

Hydrogen bonding and chemical reactivity, 26, 255

CUMULATIVE INDEX OF TITLES386

Hydrogen isotope effects in aromatic substitution reactions, 2, 163

Hydrogen isotope exchange reactions of organic compounds in liquid ammonia, 1, 156Hydrolysis, ester, and related reactions, general base and nucleophilic catalysis of, 5, 237

Interface, the air-water, chirality and molecular recognition in monolayers at, 28, 45Intermediates, reactive, study of, by electrochemical methods, 19, 131

Intermediates, tetrahedral, derived from carboxylic acids, spectroscopic detection andinvestigation of their properties, 21, 37

Intramolecular reactions, effective molarities for, 17, 183

Intramolecular reactions, of chain molecules, 22, 1

Ionic dissociation of carbon-carbon a-bonds in hydrocarbons and the formation of authentichydrocarbon salts, 30, 173

Ionization potentials, 4, 31

Ion-pairing effects in carbanion reactions, 15, 153

Ions, organic, charge density-NMR chemical shift correlations, 11, 125

Isomerization, permutational, of pentavalent phosphorus compounds, 9, 25

Isotope effects and quantum tunneling in enzyme-catalyzed hydrogen transfer

Part I The experimental basis, 39, 27

Isotope effects, hydrogen, in aromatic substitution reactions, 2, 163

Isotope effects, magnetic, magnetic field effects and, on the products of organic reactions,

20, 1

Isotope effects, on NMR spectra of equilibrating systems, 23, 63

Isotope effects, steric, experiments on the nature of, 10, 1

Isotope exchange reactions, hydrogen, of organic compounds in liquid ammonia, 1, 150Isotope exchange reactions, oxygen, of organic compounds, 3, 123

Isotopes and organic reaction mechanisms, 2, 1

Kinetics, and mechanisms of reactions of organic cation radicals in solution, 20, 55

Kinetics and mechanism of the dissociative reduction of C—X and X—X bonds (X ¼ O, S),

36, 85

Kinetic and mechanistic studies of the reactivity Zn–Ohn(n = 1 or 2) species in small moleculeanalogs of zinc-containing metalloenzymes, 41, 81

Kinetics and spectroscopy of substituted phenylnitrenes, 36, 255

Kinetics, of organic reactions in water and aqueous mixtures, 14, 203

Kinetics, reaction, polarography and, 5, 1

b-Lactam antibiotics, mechanisms of reactions, 23, 165

Least nuclear motion, principle of, 15, 1

Macrocyles and other concave structures, acid-base behaviour in, 30, 63

Macromolecular systems of biochemical interest,13C NMR spectroscopy in, 13, 279Magnetic field and magnetic isotope effects on the products of organic reactions,

Mechanism and reactivity in reactions of organic oxyacids of sulphur and their anhydrides,

17, 65

Mechanism and structure, in carbene chemistry, 7, 153

Mechanism and structure, in mass spectrometry: a comparison with other chemical processes,

8, 152

Mechanism and structure, in organic electrochemistry, 12, 1

Mechanism of the dissociative reduction of C—X and X—X bonds (XQO, S), kinetics and,

36, 85

Mechanisms for nucleophilic aliphatic substitution at glycosides, 41, 277

Mechanisms of hydrolysis and rearrangements of epoxides, 40, 247

Mechanisms, nitrosation, 19, 381

Mechanisms, of proton transfer between oxygen and nitrogen acids and bases in aqueoussolutions, 22, 113

Mechanisms, organic reaction, isotopes and, 2, 1

Mechanisms of reaction, in solution, entropies of activation and, 1, 1

Mechanisms of reaction, of b-lactam antibiotics, 23, 165

Mechanisms of solvolytic reactions, medium effects on the rates and, 14, 10

Mechanistic analysis, perspectives in modern voltammeter: basic concepts and, 32, 1Mechanistic applications of the reactivity–selectivity principle, 14, 69

Mechanistic studies, heat capacities of activation and their use, 5, 121

Mechanistic studies on enzyme-catalyzed phosphoryl transfer, 40, 49

Medium effects on the rates and mechanisms of solvolytic reactions, 14, 1

Meisenheimer complexes, 7, 211

Metal complexes, the nucleophilicity of towards organic molecules, 23, 1

Methyl transfer reactions, 16, 87

Micellar catalysis in organic reactions: kinetic and mechanistic implications, 8, 271

Micelles, aqueous, and similar assemblies, organic reactivity in, 22, 213

Micelles, membranes and other aqueous aggregates, catalysis by, as models of enzyme action,

17, 435

Molecular recognition, chirality and, in monolayers at the air-water interface, 28, 45Molecular structure and energy, calculation of, by force-field methods, 13, 1

N-Arylnitrinium ions, 36, 167

Neighbouring group participation by carbonyl groups in ester hydrolysis, 28, 171

Nitration, nitrosation, and halogenation, diffusion control and pre-association in, 16, 1Nitrosation, mechanisms, 19, 381

Nitrosation, nitration, and halogenation, diffusion control and pre-association in, 16, 1NMR chemical shift-charge density correlations, 11, 125

NMR measurements of reaction velocities and equilibrium constants as a function oftemperature, 3, 187

NMR spectra of equilibriating systems, isotope effects on, 23, 63

NMR spectroscopy,13

C, in macromolecular systems of biochemical interest, 13, 279Nobel Prize, Gomberg and the, 36, 59

Non-linear optics, organic materials for second-order, 32, 121

Non-planar and planar aromatic systems, 1, 203

Norbornyl cation: reappraisal of structure, 11, 179

Nuclear magnetic relaxation, recent problems and progress, 16, 239

Nuclear magnetic resonance see NMR

CUMULATIVE INDEX OF TITLES388

Nuclear motion, principle of least, 15, 1

Nuclear motion, the principle of least, and the theory of stereoelectronic control,

24, 113

Nucleophiles, partitioning of carbocations between addition and deprotonation, 35, 67Nucleophili aromatic photolabstitution, 11, 225

Nucleophilic catalysis of ester hydrolysis and related reactions, 5, 237

Nucleophilic displacement reactions, gas-phase, 21, 197

Nucleophili substitution, in phosphate esters, mechanism and catalysis of, 25, 99

Nucleophilic substitution, single electron transfer and, 26, 1

Nucleophilic substitution reactions in aqueous solution, 38, 161

Nuckophilic vinylic substitution, 7, 1

Nucleophilic vinylic substitution and vinyl cation intermediates in the reactions of vinyliodonium salts 37, 1

Nucleophilicity of metal complexes towards organic molecules, 23, 1

O—H bonds, hydrogen atom abstraction from, 9, 127

One- and two-electron oxidations and reductions of organoselenium and organotelluriumcompounds, 39, 79

Orbital interactions and long-range electron transfer, 38, 1

Organic materials for second-order non-linear optics, 32, 121

Organic reactivity, electron-transfer paradigm for, 35, 193

Organic reactivity, structure determination of, 35, 67

Orotidine monophosphate decarboxylase, the mechanism of, 38, 183

Oxyacids of sulphur and their anhydrides, mechanisms and reactivity in reactions of organic,

17, 65

Oxygen isotope exchange reactions of organic compounds, 3, 123

Partitioning of carbocations between addition of nucleophiles and deprotonation, 35, 67Perchloro-organic chemistry: structure, spectroscopy and reaction pathways, 25, 267Permutations isomerization of pentavalent phosphorus compounds, 9, 25

Phase-transfer catalysis by quaternary ammonium salts, 15, 267

Phenylnitrenes, Kinetics and spectroscopy of substituted, 36, 255

Phosphate esters, mechanism and catalysis of nuclcophilic substitution in, 25, 99

Phosphorus compounds, pentavalent, turnstile rearrangement and pseudoration in

permutational isomerization, 9, 25

Photochemistry, of aryl halides and related compounds, 20, 191

Photochemistry, of carbonium ions, 9, 129

Photodimerization and photopolymerization of diolefin crystals, 30, 117

Photosubstitution, nucleophilic aromatic, 11, 225

Planar and non-planar aromatic systems, 1, 203

Polarizability, molecular refractivity and, 3, 1

Polarography and reaction kinetics, 5, 1

Polypeptides, calculations of conformations of, 6, 103

Pre-association, diffusion control and, in nitrosation, nitration, and halogenation, 16, 1Principle of non-perfect synchronization, 27, 119

Products of organic reactions, magnetic field and magnetic isotope effects on, 30, 1

Protic and dipolar aprotic solvents, rates of bimolecular substitution reactions in,

5, 173

Protolytic processes in H2O—D2O mixtures, 7, 259

Proton transfer between oxygen and nitrogen acids and bases in aqueous solution,

mechanisms of, 22, 113

Protonation and solvation in strong aqueous acids, 13, 83

Protonation sites in ambident conjugated systems, 11, 267

Pseudorotation in isomerization of pentavalent phosphorus compounds, 9, 25

Pyrolysis, gas-phase, of small-ring hydrocarbons, 4, 147

Radiation techniques, application to the study of organic radicals, 12, 223

Radical addition reactions, gas-phase, directive effects in, 16, 51

Radical rearrangement reactions, charge distribution and charge separation in, 38, 111Radicals, cation in solution, formation, properties and reactions of, 13, 155

Radicals, organic application of radiation techniques, 12, 223

Radicals, organic cation, in solution kinetics and mechanisms of reaction of, 20, 55Radicals, organic free, identification by electron spin resonance, 1, 284

Radicals, short-lived organic, electron spin resonance studios of, 5, 53

Rates and mechanisms of solvolytic reactions, medium effects on, 14, 1

Reaction kinetics, polarography and, 5, 1

Reaction mechanisms, in solution, entropies of activation and, 1, 1

Reaction mechanisms, use of volumes of activation for determining, 2, 93

Reaction velocities and equilibrium constants, NMR measurements of, as a function oftemperature, 3, 187

Reactions, in dimethyl sulphoxide, physical organic chemistry of, 14, 133

Reactions, of hydrated electrons with organic compounds, 7, 115

Reactive intermediates, study of, by electrochemical methods, 19, 131

Reactivity, organic, a general approach to; she configuration mixing model, 21, 99

Reactivity indices in conjugated molecules, 4, 73

Reactivity-selectivity principle and its mechanistic applications, 14, 69

Rearrangements, degenerate carbocation, 19, 223

Receptor molecules, redox-active, electrochemical recognition of charged and neutral guestspecies by, 31, 1

Redox and recognition processes, interplay between, 37, 315

Redox systems, organic, with multiple electrophores, electron storage and transfer in, 28, 1Reduction.of C—X and X—X bonds (XQO, S), kinetics and mechanism of the dissociative,

36, 85

Refractivity, molecular, and polarizability, 3, 1

Relaxation, nuclear magnetic, recent problems and progress, 16, 239

Selectivity of solvolyses and aqueous alcohols and related mixtures, solvent-induced changes

in, 27, 239

Short-lived organic radicals, electron spin resonance studies of, 5, 53

Small-ring hydrocarbons, gas-phase pyrolysis of, 4, 147

Solid state, tautomerism in the 32, 129

Solid-state chemistry, topochemical phenomena in, 15, 63

Solids, organic, electrical conduction in, 16, 159

Solutions, reactions in, entropies of activation and mechanisms, 1, 1

Solvation and protonation in strong aqueous acids, 13, 83

CUMULATIVE INDEX OF TITLES390

Solvent effects, reaction coordinates, and reorganization energies on nucleophilic substitutionreactions in aqueous solution, 38, 161

Solvent, protic and dipolar aprotic, rates of bimolecular substitution-reactions in, 5, 173Solvent-induced changes in the selectivity of solvolyses in aqueous alcohols and relatedmixtures, 27, 239

Solvolytic reactions, medium effects on the rates and mechanisms of, 14, 1

Spectroscopic detection of tetrahedral intermediates derived from carboxylic acids and theinvestigation of their properties, 21, 37

Spectroscopic observations ofalkylcarbonium ions in strong acid solutions, 4, 305

Spectroscopy,13C NMR in macromolecular systems of biochemical interest, 13, 279Spectroscopy of substituted phenylnitrenes, kinetics and 36, 255

Spin alignment, in organic molecular assemblies, high-spin organic molecules and 26, 179Spin trapping, 17, 1

Spin trapping, and electron transfer, 31, 91

Stability and reactivity of crown-ether complexes, 17, 279

Stereochemistry, static and dynamic, of alkyl and analogous groups, 25, 1

Stereoelectronic control, the principle of least nuclear motion and the theory of, 24, 113Stereoselection in elementary steps of organic reactions, 6, 185

Steric isotope effects, experiments on the nature of, 10, 1

Structure, determination of organic reactivity, 35, 67

Structure and mechanism, in curbene chemistry, 7, 153

Structure and mechanism, in organic electrochemistry, 12, 1

Structure and reactivity of carbencs having aryl substitutents, 22, 311

Structure and reactivity of hydrocarbon radical cations, 38, 87

Structure of electronically excited molecules, 1, 365

Substitution, aromatic, a quantitative treatment of directive effects in, 1, 35

Substitution, nueleophilic vinylic, 7, 1

Substitution reactions, aromatic, hydrogen isotope effects in, 2, 163

Substitution reactions, bimolecular, in protic and dipolar aprotic solvents, 5, 173

Sulphur, organic oxyacids of, and their anhydrides, mechanisms and reactivity in reactions of,

17, 65

Superacid systems, 9, 1

Tautomerism in the solid state, 32, 219

Temperature, NMR measurements of reaction velocities and equilibrium constants as afunction of, 3, 187

Tetrahedral intermediates, derived from carboxylic acids, spectroscopic detection and theinvestigation of their properties, 21, 37

The interpretation and mechanistic significance of activation volumes for organometallicreactions, 41, 1

The physical organic chemistry of very high-spin polyradicals, 40, 153

Thermodynamic stabilities of carbocations, 37, 57

Topochemical phenomena in solid-slate chemistry, 15, 63

Transition state analysis using multiple kinetic isotope effects, 37, 239

Transition state structure, crystallographic approaches to, 29, 87

Transition state structure, in solution, effective charge and 27, 1

Transition stale structure, secondary deuterium isotope effects and, 31, 143

Transition states, structure in solution, cross-interaction constants and, 27, 57

Transition states, the stabilization of by cyclodextrins and other catalysts, 29, 1

Transition states, theory revisited, 28, 139

Tritiated molecules, gaseous carbonium ions from the decay of, 8, 79

Tritium atoms, energetic reactions with organic compounds, 2, 201

Turnstile rearrangements in isomerization of pentavalent phosphorus compounds, 9, 25

Unsaturated compounds, basicity of, 4, 195

Using kinetic isotope effects to determine the structure of the transition states of SN2reactions, 41, 219

Vinyl cation intermediates, 37, 1

Vinyl cations, 9, 185

Vinyl iodonium salts, 37, 1

Vinylic substitution, nuclephilic, 7, 1; 37, 1

Voltammetry, perspectives in modern: basic concepts and mechanistic analysis, 32, 1Volumes of activation, use of, for determining reaction mechanisms, 2, 93

Water and aqueous mixtures, kinetics of organic reactions in, 14, 203

Yukawa–Tsuno relationship in carborationic systems, the, 32, 267

CUMULATIVE INDEX OF TITLES392

DIMITRIANTONIOU, JODIBASNER, SARANU´N˜EZ and STEVEND SCHWARTZ

Department of Biophysics, Albert Einstein College of Medicine, Bronx, New York,USA

1 Introduction 315

2 Proton transfer and rate-promoting vibrations 317

Quantum theory of proton transfer 317

Rate-promoting vibrations 320

Computational signature of promoting vibrations 325

Experimental signature of promoting vibrations 326

Four objections to promoting vibrations 326

3 Examples of rate-promoting motions in enzymatic systems 328

Horse liver alcohol dehydrogenase 328

Lactate dehydrogenase 330

Human purine nucleoside phosphorylase 335

4 Description in atomic detail of correlated protein motions 342

Transition path sampling 342

TS, lowering the energetic barrier to reaction In the ground state destabilizationpicture2the role of the enzyme is to make the reactants less stable, leading again to alower barrier to reaction

In the last few years it has been suggested by us and other groups that enzymedynamics may play a role in catalysis We do not claim that these dynamical effectscontribute more to catalysis than the standard binding energy effects, but thatthey should be taken into account in the interpretation of, for example, kineticisotope effects (KIE) measurements3 and that they may provide insight to somepuzzling data In particular, our work on the relation between catalysis and enzymedynamics originated in the effort to understand some unusual properties of the

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ADVANCES IN PHYSICAL ORGANIC CHEMISTRY r2006 Elsevier Ltd.

following three systems:

1 It is now widely accepted that for some enzymes (e.g., liver alcohol dehydrogenase,thermophilic alcohol dehydrogenase, etc.) proton transfer proceeds through quan-tum tunneling The high activation barriers in these systems were consistent withtunneling However, the KIE were modest, when tunneling would seem to implyhigh KIE

2 The enzyme lactate dehydrogenase (LDH) catalyzes the interconversion of lactate

to pyruvate There are two isoforms in the body to accommodate differentsubstrates Despite the fact that the active site is identical in these two isoforms,one favors the production of lactate and the other production of pyruvate

3 Crystal structures of human purine nucleoside phosphorylase with several TSanalogs showed an unusual geometric arrangement of three oxygens, lying in aclose stack One may question whether this geometry serves a catalytic purpose

We will show that the answers to all the three of these puzzles involve the dynamics

of the enzyme There has recently been a disagreement among some authorsregarding the meaning of the term ‘‘dynamical’’, with some suggesting that theterm should be reserved for non-equilibrium motions, while others would use it forequilibrium motions For clarity, we will define the meaning we give to the term

‘‘dynamical’’ in this review

Let us assume that a variable A(t) is coupled to the reaction coordinate and that(A) is its mean value If a measurement of some property P depends on (A), but not

on the particular details of the time dependence of A(t), then we will call it a

‘‘statistical’’ dependence If the property P depends on particular details of thedynamics of A(t) we will call it a ‘‘dynamical’’ dependence Note that in this defi-nition it is not the mode A(t) alone that causes dynamical effects, but it also depends

on the timescale of the measured property P Promoting vibrations (to be discussed

in Sections 2–4) are a ‘‘dynamic’’ effect in this sense, since their dynamics is coupled

to the reaction coordinate and have similar timescales Conformation fluctuationsthat enhance tunneling (to be discussed in Section 5) are a ‘‘statistical’’ effect: thereaction rate is the sum of transition state theory (TST) rates for barriers corre-sponding to some configuration, weighted by the probability that the system reachesthat configuration This distinction between dynamic and statistical phenomena inproteins was first made in the classic paper of Agmon and Hopfield.4

We will discuss three kinds of motions:

1 ‘‘Rate-promoting’’ quasi-harmonic motions, a fast sub-ps effect we and otherhave proposed (Section 3)

2 Other kinds of sub-ps motions that involve correlated motions of several residues(Section 4)

3 Conformation fluctuations (Section 5)

The structure of this review is as follows In Section 2 we will review the concept of

‘‘rate-promoting’’ vibrations We will first need to review briefly the theory of

D ANTONIOU ET AL.316

quantum hydrogen/hydride transfer, because it is the large proton mass (relative to

an electron) that makes the reaction rate very sensitive to motions that modulate itstransfer distance We will then identify the experimental and computational signa-tures of these promoting vibrations We will close with investigating some objections

to the possibility of existence of such promoting vibrations In Section 3 we willapply the theory of Section 2 to the three enzymatic systems that we mentionedearlier in the Introduction

In Section 4 we will use two theoretical techniques (transition path sampling(TPS) and essential dynamics (ED)) to analyze molecular dynamics trajectories Wewill explain how we were able to identify in atomic detail collective motions thataffect catalysis

Finally, in Section 5 we will briefly discuss recent work by Truhlar, Brooks, andHammes-Schiffer on the relation of conformation fluctuations and catalysis indihydrofolate reductase (DHFR) and we will propose a new method for studyingmuch slower motions (such as conformation fluctuations) that may affect catalysis.This review is not meant to be comprehensive of all work on enzyme dynamicsand catalysis The emphasis will be on the work done by our group, mainly on fastsub-ps enzyme motions, while other groups have studied mostly conformationalfluctuations When necessary, we will provide brief descriptions and references to thecurrent work by other groups

2 Proton transfer and rate-promoting vibrations

We first identified rate-promoting vibrations in enzymatic systems where protontransfer proceeds via quantum tunneling (in this theoretical section, we will use theterms hydrogen, hydride, proton as if they were equivalent) In order to understandwhy systems with proton tunneling are good candidates for identifying promotingvibrations, we must review the modern theory of quantum charge transfer in con-densed phase, which will be the subject of this section

Excellent recent reviews of the experimental work in tunneling in enzymes havebeen written by Scrutton,5Romesberg and Schowen,6and Kohen.7

QUANTUM THEORY OF PROTON TRANSFER

The reaction rate of proton transfer in condensed phases depends on several meters: temperature, potential barrier height, transfer distance, reactant frequency,strength of coupling to the environment For different values of these parameters,different physical mechanisms dominate which have been described by differenttheoretical models, in the chronological order they were studied, the parameter re-gions were:

para-Region I: The dynamics is over the barrier (as described by TST) or just below thebarrier (small quantum corrections)

Region II: The dynamics takes place by tunneling from excited energy states in thereactant well (moderate to large quantum effects)