Computational screening of novel thiamine-catalyzed decarboxylation reactions of 2-keto acids
Rajeev S. Assary and Linda J. Broadbelt*
Department of Chemical and Biological Engineering,
Northwestern University, Evanston, Illinois 60208
Corresponding author: Linda J. Broadbelt
Phone: (847) 491-5351; email:
Molecular geometries (B3LYP/6-31+G*)
The intermediates/molecules in the thiamine catalyzed decarboxylation mechanism explained in this paper listed down and their optimized Cartesian coordinates are given.
Step1. Isolated thiamine and ketoacid (A)
Step2: Transition state (TS1) of carbon-carbon bond formation
Step3: Initial complex (C)
Step4: Proton transfer transition state (TS2, D)
Step5: Tetrahedral intermediate, LThDP analogue (E)
Step6: Transition state (TS3) of carbon-carbon bond breaking (F)
Step 7: Enamine/carbanion formation (G)
optimized structure of Thiamine diphosphate model ( ThDP)
33
scf done: -1084.112603
N -26.939420 -64.698994 22.411480
C -25.690773 -65.025750 22.784570
C -24.909601 -63.997611 23.559034
N -25.069152 -66.178487 22.512006
C -25.731574 -67.105420 21.792976
N -25.099224 -68.288323 21.576242
C -27.058166 -66.858946 21.332451
C -27.589547 -65.631233 21.698320
C -27.869926 -67.890086 20.590251
N -27.403087 -68.164113 19.203853
C -26.476134 -69.125852 19.021144
S -26.145571 -69.153945 17.329492
C -27.274986 -67.860914 16.930869
C -27.867684 -67.435428 18.080346
C -28.899894 -66.357412 18.231784
C -27.464886 -67.372879 15.520786
C -26.290039 -66.525729 14.995850
H -24.268780 -64.480597 24.302233
H -24.257698 -63.434488 22.877794
H -25.586817 -63.290104 24.043328
H -24.125454 -68.320973 21.851621
H -27.831569 -68.855513 21.102900
H -28.917073 -67.579793 20.546998
H -29.118189 -65.904132 17.261990
H -29.845160 -66.746790 18.631364
H -28.558059 -65.558780 18.899845
H -27.613577 -68.235255 14.857447
H -28.390004 -66.786890 15.463587
H -26.139504 -65.635216 15.616549
H -25.355547 -67.097894 14.999345
H -25.393262 -68.890315 20.799048
H -28.612429 -65.379254 21.414147
H -26.483113 -66.199181 13.967248
pyruvic acid
10
scf done: -342.423425
C 1.596976 -1.028049 0.337423
C 0.675658 -0.099867 -0.392186
O 1.029813 0.810625 -1.122657
C -0.850938 -0.313349 -0.204478
O -1.312438 -1.183135 0.494860
O -1.588839 0.563439 -0.895820
H 1.390880 -2.064382 0.043976
H 2.634925 -0.769213 0.121077
H 1.404336 -0.973370 1.415559
H -0.967682 1.154834 -1.374616
pyruvic acid: TS1 (B)
43
scf done: -1426.529826
C -3.007260 -0.089614 -1.403638
C -1.903333 -0.551564 -0.693954
C -2.205634 -1.113216 0.577719
N -3.462863 -1.070497 1.067695
C -4.425112 -0.545206 0.306417
N -4.263148 -0.073236 -0.943553
C -0.518705 -0.502332 -1.294275
N 0.417774 0.476311 -0.662682
C 0.252941 1.881422 -0.771568
C 1.257449 2.554083 -0.143106
S 2.380255 1.393698 0.545942
C 1.500080 0.028921 -0.006270
C -0.888285 2.486835 -1.532739
C 2.129430 -2.190462 0.526205
C 3.252248 -2.085699 -0.530435
O 4.330472 -1.572861 -0.338748
C 1.459308 4.036697 0.016618
C 0.957009 4.582999 1.366879
N -1.271115 -1.694076 1.379256
C -5.815516 -0.489561 0.879710
O 1.148113 -2.901273 0.225677
C 2.508241 -1.901127 1.956749
O 2.912151 -2.679867 -1.687749
H -6.510573 -1.039929 0.235211
H -5.834898 -0.914630 1.885182
H -6.166963 0.548430 0.914965
H -1.660034 -2.177735 2.180301
H -0.012669 -1.466037 -1.218900
H -0.590269 -0.251838 -2.357775
H -0.725647 3.560642 -1.652555
H -0.981274 2.057566 -2.536992
H -1.846634 2.348132 -1.022205
H 2.525794 4.269104 -0.095920
H 0.949513 4.559795 -0.801234
H -0.117268 4.404898 1.488631
H 1.473973 4.102813 2.205189
H -0.433678 -2.120877 0.978926
H -2.870835 0.295331 -2.414963
H 1.135584 5.662517 1.431908
H 2.028678 -3.083835 -1.529118
H 2.931821 -2.826349 2.373142
H 3.266549 -1.120949 2.030690
H 1.624348 -1.634672 2.540450
pyruvic acid: initial complex (C)
43
scf done: -1426.551962
C 1.471510 0.143630 0.075492
N 0.384615 0.520765 -0.613908
C 0.189144 1.915266 -0.689734
C 1.151676 2.614072 -0.021271
S 2.299216 1.512905 0.688275
C -0.545374 -0.450993 -1.300537
C -1.937010 -0.481897 -0.724857
C -3.032899 -0.092128 -1.485562
N -4.301879 -0.099777 -1.061737
C -4.481332 -0.516972 0.206739
N -3.524670 -0.953952 1.026643
C -2.248246 -0.978707 0.576951
N -1.309154 -1.461008 1.421954
C -5.893354 -0.506645 0.728698
C -0.951320 2.508300 -1.460323
C 1.291669 4.100169 0.176451
C 0.651391 4.608501 1.482727
C 2.014801 -1.284743 0.279448
C 2.855210 -1.345562 1.582598
C 3.023271 -1.533549 -0.930199
O 2.726266 -2.687110 -1.511229
O 1.050391 -2.245436 0.241482
O 3.931312 -0.792922 -1.247069
H -6.506665 -1.216743 0.160675
H -5.915369 -0.779395 1.785760
H -6.341542 0.483664 0.590701
H -1.677200 -1.885538 2.264900
H -0.052731 -1.419626 -1.206040
H -0.574274 -0.156884 -2.353568
H -0.800991 3.584939 -1.564527
H -1.022807 2.087561 -2.468703
H -1.912360 2.346638 -0.963265
H 2.355604 4.366493 0.161409
H 0.841713 4.616197 -0.679134
H -0.421695 4.389861 1.508125
H 1.110946 4.139044 2.359620
H -0.398610 -1.816065 1.061642
H -2.880014 0.250253 -2.510509
H 0.782771 5.692669 1.571332
H 1.910752 -2.976825 -0.972455
H 3.224691 -2.370121 1.681570
H 3.717720 -0.669178 1.578228
H 2.215958 -1.128418 2.444878
pyruvic Acid: transition state 2 (TS2, D)
43
scf done: -1426.549349
C 0.190741 1.902749 -0.636005
N 0.395791 0.510095 -0.555435
C 1.485832 0.143614 0.137583
S 2.301702 1.521704 0.747748
C 1.146742 2.610858 0.031237
C -0.513853 -0.466764 -1.254412
C -1.922236 -0.496896 -0.717922
C -2.272319 -0.948265 0.588565
N -3.561088 -0.919006 0.997112
C -4.495118 -0.519469 0.132615
N -4.277101 -0.145530 -1.143131
C -2.996050 -0.142337 -1.526762
N -1.358127 -1.388904 1.485623
C -5.922719 -0.502227 0.608897
C 2.060198 -1.250044 0.320849
C 2.848444 -1.621271 -1.039436
O 2.367210 -2.755497 -1.445957
C 1.277437 4.098391 0.223514
C 0.634648 4.607925 1.528059
C -0.951333 2.485746 -1.411889
O 1.088918 -2.233206 0.433974
C 3.068075 -1.295428 1.485471
O 3.724568 -0.919070 -1.515868
H -6.516061 -1.225285 0.036272
H -5.977950 -0.752113 1.670321
H -6.368162 0.483912 0.435966
H -1.751280 -1.789172 2.329012
H -0.028225 -1.434778 -1.158606
H -0.517175 -0.182924 -2.310795
H -0.805785 3.562451 -1.521655
H -1.018497 2.059462 -2.418115
H -1.912698 2.322427 -0.916049
H 2.339724 4.371153 0.206602
H 0.824127 4.608166 -0.633937
H -0.437190 4.383355 1.554417
H 1.096951 4.144453 2.406716
H -0.444549 -1.755497 1.172315
H -2.812762 0.166578 -2.557188
H 0.759933 5.693114 1.612502
H 1.569315 -2.859493 -0.583418
H 3.433584 -2.323110 1.561758
H 3.931594 -0.641070 1.322311
H 2.577439 -1.038184 2.431022
pyruvic acid: intermediate E
43
scf done: -1426.558725
C -27.238404 -67.258391 18.219933
N -26.599449 -68.113557 19.138712
C -25.692350 -68.943044 18.595029
S -25.569733 -68.677638 16.906034
C -26.789024 -67.433434 16.944056
C -27.001576 -68.171404 20.583805
C -26.781704 -66.893487 21.355798
C -25.518488 -66.271107 21.558113
N -25.425784 -65.116064 22.250734
C -26.536524 -64.600851 22.782567
N -27.767205 -65.140162 22.699093
C -27.852791 -66.267190 21.985289
C -26.406414 -63.320930 23.562866
N -24.358743 -66.760423 21.043864
C -27.182801 -66.713498 15.681892
C -26.275495 -65.513175 15.349832
C -28.316137 -66.309401 18.649332
H -25.404893 -62.900580 23.451019
H -27.156367 -62.595468 23.229942
H -26.596525 -63.512619 24.626206
H -23.522277 -66.291936 21.370982
H -26.469115 -69.013343 21.019359
H -28.063920 -68.434336 20.596162
H -28.807279 -65.891964 17.767850
H -29.084173 -66.811834 19.246508
H -27.922750 -65.479230 19.243231
H -27.173188 -67.423748 14.846006
H -28.221033 -66.376092 15.774996
H -26.298709 -64.766875 16.151401
H -25.234668 -65.827151 15.212983
H -24.267986 -67.756536 20.830260
H -28.850096 -66.702755 21.906807
H -26.608648 -65.032106 14.423504
C -24.946309 -70.053710 19.272091
O -24.296835 -69.570572 20.442826
H -24.625416 -70.229388 21.121850
C -23.931327 -70.737886 18.351367
H -23.429690 -71.519278 18.929270
H -24.423675 -71.215679 17.498871
H -23.166396 -70.034366 18.000092
C -26.047361 -71.168910 19.751985
O -25.906393 -71.421826 20.974475
O -26.820421 -71.575828 18.880093
pyruvic acid: transition state 3 (TS3, F)
43
scf done: -1426.549728
C -2.361164 -0.778577 0.841565
C -1.991387 -0.527948 -0.508998
C -3.042028 -0.152278 -1.338370
N -4.306574 0.033972 -0.940328
C -4.533018 -0.162263 0.370594
N -3.624796 -0.564517 1.263226
C -0.595016 -0.705220 -1.065576
N 0.432499 0.228368 -0.530079
C 1.522467 -0.173816 0.212673
S 2.544883 1.210609 0.548415
C 1.516924 2.277377 -0.406885
C 0.451667 1.596793 -0.894360
C 1.933807 -1.443671 0.642458
O 0.951512 -2.445913 0.753913
C -0.634214 2.172778 -1.754297
C 1.889295 3.727861 -0.544655
C 1.597973 4.570007 0.712680
C -5.936329 0.071367 0.862501
N -1.480815 -1.212882 1.784599
C 3.041760 -1.561332 1.668204
C 3.037686 -2.189830 -1.188064
O 3.910770 -1.422297 -1.434873
O 2.409151 -3.201038 -1.355548
H -6.624185 -0.635083 0.382377
H -5.990497 -0.053572 1.945886
H -6.270745 1.078447 0.589124
H -1.900277 -1.480091 2.666523
H -0.222706 -1.708816 -0.878801
H -0.626354 -0.573632 -2.152500
H -0.380812 3.197945 -2.030965
H -0.766796 1.608208 -2.684273
H -1.599312 2.194114 -1.238263
H 2.956854 3.802338 -0.792302
H 1.353931 4.154973 -1.399732
H 0.529857 4.554069 0.956665
H 2.145501 4.190880 1.582947
H -0.641330 -1.717867 1.508663
H -2.853174 0.014446 -2.399683
H 1.898755 5.611967 0.552453
H 1.216352 -3.171554 0.148893
H 3.319519 -2.614305 1.781695
H 3.941451 -1.013608 1.367044
H 2.728944 -1.191617 2.657224
pyruvic acid: enamine (G)
40
scf done: -1237.965454
C -2.371176 -0.202582 0.940744
N -2.020687 0.050524 -0.423054
C -3.157591 -0.100381 -1.263519
S -4.473727 -0.968100 -0.411739
C -3.605181 -0.714643 1.133304
C -0.746182 -0.538294 -0.934098
C 0.522786 0.146154 -0.483048
C 0.816262 1.521363 -0.706288
N 1.993965 2.051053 -0.324489
C 2.888692 1.247685 0.263354
N 2.723253 -0.060945 0.506888
C 1.540533 -0.572206 0.125512
N -0.066662 2.373454 -1.288630
C 4.186056 1.878785 0.696231
C -3.279235 0.394551 -2.510565
C -4.458003 0.227299 -3.415110
C -4.319756 -1.055213 2.410974
C -5.433184 -0.063167 2.799297
C -1.392163 0.159632 2.021833
O -2.184679 1.087149 -3.043034
H 4.921977 1.107679 0.934744
H 4.572926 2.538189 -0.087385
H 4.024549 2.496362 1.589375
H 0.278491 3.294834 -1.520446
H -0.813969 -0.497414 -2.023807
H -0.692248 -1.602456 -0.656069
H -1.867939 0.108265 3.004130
H -0.521206 -0.504688 2.041229
H -1.017682 1.179323 1.877409
H -4.753515 -2.061361 2.314399
H -3.589167 -1.121581 3.224625
H -5.025149 0.942829 2.950536
H -6.198564 0.000654 2.018039
H -0.900619 2.032330 -1.753570
H 1.400564 -1.636127 0.322743
H -5.921754 -0.378550 3.729215
H -2.444622 1.495671 -3.882318
H -4.262061 -0.484795 -4.230605
H -5.331901 -0.131081 -2.863290
H -4.735408 1.189245 -3.873759
2-keto butanoic acid
13
scf done: -381.736975
C -2.159089 -1.074965 0.023464
C -1.419560 0.197898 0.497088
C -0.199553 0.460369 -0.339140
O -0.135749 1.277197 -1.244480
C 1.073481 -0.387641 -0.061097
O 2.078710 -0.104795 -0.898313
O 1.142155 -1.209549 0.821664
H -1.114279 0.068045 1.541169
H -2.072637 1.071929 0.415617
H -3.050139 -1.227620 0.640876
H -2.480291 -0.978566 -1.019304
H -1.523990 -1.960670 0.118982
H 1.761130 0.599220 -1.505652
2-keto-butanoic acid TS1 (B)
46
scf done: -1465.843547
C -27.480704 -66.731209 18.026590
N -27.554628 -67.695154 19.064499
C -27.071970 -68.919895 18.803443
S -26.461784 -68.917108 17.201203
C -26.888352 -67.239901 16.909885
C -28.197602 -67.415461 20.385044
C -27.477403 -66.417023 21.257251
C -26.241821 -66.677379 21.913217
N -25.636835 -65.717713 22.646145
C -26.252861 -64.542318 22.787133
N -27.458868 -64.224218 22.280670
C -28.032680 -65.171381 21.530374
N -25.587895 -67.865340 21.827293
C -25.555629 -63.483147 23.597853
C -27.017280 -70.781486 20.150564
C -28.358836 -71.251714 19.533442
O -29.394757 -71.015357 20.359558
C -26.576165 -66.564044 15.602271
C -25.125621 -66.053426 15.505855
C -28.040848 -65.349935 18.190311
O -27.074574 -70.361306 21.329641
C -25.771196 -71.422735 19.573295
C -24.457250 -70.815287 20.061529
O -28.477289 -71.799764 18.462015
H -25.426372 -62.573861 22.999528
H -26.168485 -63.210022 24.464953
H -24.581449 -63.838605 23.939508
H -24.793283 -67.952455 22.449360
H -28.274127 -68.387520 20.872662
H -29.216256 -67.065947 20.188030
H -28.056523 -64.839523 17.224340
H -29.070616 -65.370933 18.564664
H -27.448662 -64.741906 18.881638
H -26.771930 -67.263177 14.779543
H -27.268608 -65.726537 15.456380
H -24.913888 -65.318638 16.290568
H -24.408553 -66.874951 15.613051
H -26.082857 -68.734833 21.622700
H -29.008697 -64.917108 21.115031
H -24.952851 -65.577222 14.533869
H -25.831956 -72.477351 19.888716
H -25.836832 -71.443592 18.482366
H -23.607435 -71.363773 19.640392
H -24.369035 -69.765986 19.759902
H -24.383671 -70.862827 21.153016
H -28.990815 -70.654520 21.183301
2-keto-butanoic acid: initial complex (C)
46
scf done: -1465.865096
C -28.083475 -65.068100 21.512898
C -27.492659 -66.289462 21.211392
C -26.233891 -66.525569 21.841232
N -25.653183 -65.555806 22.586384
C -26.310938 -64.409651 22.764722
N -27.533073 -64.118378 22.277857
C -28.204465 -67.302546 20.353758
N -27.523736 -67.600165 19.038187
C -27.438512 -66.634151 18.014288
C -26.850357 -67.122226 16.884195
S -26.419457 -68.793045 17.114296
C -27.028715 -68.805364 18.715905
C -27.979747 -65.248115 18.192251
C -26.534465 -66.419658 15.590167
C -25.124270 -65.799749 15.557623
N -25.555845 -67.686746 21.709806
C -25.644779 -63.347376 23.597927
C -27.054069 -70.092915 19.564764
C -25.921023 -71.075031 19.121718
C -24.518832 -70.641576 19.555321
C -28.424578 -70.811980 19.182493
O -28.797201 -71.054905 18.052899
O -27.049533 -69.860524 20.906397
O -29.071768 -71.128372 20.295481
H -25.576068 -62.410792 23.032724
H -26.247637 -63.138120 24.489667
H -24.646442 -63.667083 23.903313
H -24.731174 -67.766001 22.292410
H -28.275238 -68.268833 20.854317
H -29.208491 -66.948556 20.102733
H -27.962204 -64.723882 17.234446
H -29.017428 -65.258497 18.542525
H -27.392538 -64.666585 18.908624
H -26.642724 -67.129112 14.760735
H -27.284664 -65.639946 15.416107
H -25.001714 -65.054616 16.351217
H -24.351461 -66.564666 15.692383
H -26.043163 -68.564609 21.435323
H -29.071540 -64.836591 21.111366
H -24.949482 -65.307036 14.594677
H -26.162871 -72.030078 19.602837
H -25.967800 -71.261197 18.040504
H -23.781451 -71.397624 19.260914
H -24.215643 -69.689304 19.103406
H -24.476538 -70.529361 20.642653
H -28.447888 -70.742139 21.003718
2-keto-butanoic acid: transition state 2 (TS2, D)
46
scf done: -1465.862559
C -26.993212 -68.801396 18.733446
N -27.506887 -67.599633 19.049454
C -27.436356 -66.640797 18.016754
C -26.845431 -67.128826 16.888954
S -26.388782 -68.791536 17.128441
C -28.197740 -67.295780 20.355850
C -27.489039 -66.286698 21.222980
C -28.076061 -65.059418 21.510595
N -27.528622 -64.108897 22.275989
C -26.314692 -64.403695 22.779834
N -25.663622 -65.556511 22.617169
C -26.241926 -66.524931 21.871446
N -25.564836 -67.691824 21.758171
C -25.652968 -63.342706 23.617522
C -27.993083 -65.259796 18.186073
C -26.545153 -66.434095 15.587023
C -25.138006 -65.808643 15.535133
C -27.030298 -70.090762 19.534275
O -27.063813 -69.898887 20.906190
C -25.915754 -71.084176 19.110785
C -24.505541 -70.674655 19.546207
C -28.452662 -70.789764 19.197244
O -29.036785 -71.000224 20.334938
O -28.814144 -71.050177 18.061971
H -25.621258 -62.393488 23.071260
H -26.238062 -63.167601 24.528608
H -24.641091 -63.645486 23.894295
H -24.753618 -67.773480 22.358930
H -28.299233 -68.255941 20.856903
H -29.194821 -66.931153 20.093780
H -27.969301 -64.737406 17.227546
H -29.035007 -65.278720 18.523561
H -27.419059 -64.670588 18.906878
H -26.659256 -67.150102 14.764011
H -27.300365 -65.658984 15.414842
H -25.010449 -65.056727 16.321571
H -24.360376 -66.569092 15.667551
H -26.052302 -68.563239 21.497297
H -29.057822 -64.824208 21.096508
H -24.975349 -65.322699 14.566660
H -26.176534 -72.034769 19.589957
H -25.963061 -71.271562 18.030238
H -23.780844 -71.443062 19.252541
H -24.185205 -69.727771 19.094845
H -24.459234 -70.564162 20.633958
H -28.183657 -70.515857 20.994977
2-keto-butanoic acid: intermediate E
46
scf done: -1465.870935
C -27.338632 -66.651073 18.093765
C -27.375908 -67.630875 19.126239
C -26.837851 -68.865690 18.781540
N -26.268597 -69.151361 17.604647
C -26.225102 -68.136146 16.723213
N -26.737095 -66.917493 16.916792
C -28.002639 -67.432274 20.484911
N -27.373244 -66.359321 21.326398
C -28.041966 -65.283163 21.785248
S -27.057023 -64.383376 22.864129
C -25.723596 -65.489545 22.684750
C -26.061063 -66.492389 21.825672
C -29.488170 -64.947090 21.597465
O -29.895277 -65.139918 20.250266
C -25.188501 -67.649027 21.442358
C -24.428790 -65.242418 23.412298
C -23.475207 -64.287810 22.668177
C -25.530079 -68.391767 15.413319
N -27.859571 -65.403364 18.239552
C -29.877729 -63.530335 22.067115
C -29.386872 -62.387127 21.168980
C -30.336454 -66.035351 22.511379
O -30.038879 -66.087105 23.705871
O -31.172815 -66.634935 21.792452
H -25.935193 -67.747233 14.629277
H -24.458820 -68.169832 15.511549
H -25.626304 -69.443228 15.130605
H -27.881507 -64.853449 17.389180
H -29.059902 -67.191497 20.421935
H -27.924824 -68.357664 21.063510
H -24.282074 -67.638617 22.050970
H -25.686479 -68.609726 21.611170
H -24.890753 -67.608228 20.390625
H -24.649764 -64.837924 24.407763
H -23.929127 -66.202071 23.584782
H -23.200905 -64.688987 21.686333
H -23.936218 -63.305894 22.513316
H -28.614633 -65.239355 18.908662
H -26.866129 -69.683658 19.503032
H -22.556746 -64.142920 23.247851
H -30.973782 -63.518371 22.088613
H -29.562807 -63.391045 23.108069
H -29.750715 -61.426645 21.552285
H -28.293129 -62.327142 21.117877
H -29.765472 -62.509222 20.149388
H -30.668112 -65.765662 20.376326