Molecular Mechanism of NDMA Formation from N,N-Dimethylsulfamide during Ozonation: Quantum Chemical Insights into a Bromide-catalyzed Pathway. Daniela Trogolo, Brijesh Kumar Mishra, Michèle B. Heeb, Urs von Gunten, J. Samuel Arey Correspondence: samuel.arey@epfl.ch Appendix A Optimized Cartesian Coordinates (Angstroms) of all minimum energy structures. DMS 7 -0.048251 -0.268012 0.433229 16 -0.028697 0.995830 1.513946 8 1.232936 1.647997 1.314482 8 -1.288520 1.660212 1.345793 7 -0.012418 0.397806 3.065476 6 1.215486 -0.237500 3.507336 6 -1.234832 -0.226497 3.537091 1 -0.892907 -0.815534 0.469240 1 0.793048 -0.821701 0.446129 1 1.224455 -0.247058 4.596208 1 1.300640 -1.274172 3.156008 1 2.069837 0.334162 3.160829 1 -1.217944 -0.235314 4.625881 1 -2.092225 0.352381 3.210623 1 -1.337392 -1.262601 3.188729 DMS- 7 0.066894 -0.696961 0.713296 16 0.038941 0.696672 1.414875 8 1.308645 1.389083 1.244027 8 -1.179745 1.482232 1.201590 7 0.000702 0.469050 3.166939 6 1.167614 -0.219184 3.665594 6 -1.225264 -0.129503 3.630399 1 -0.904124 -0.970279 0.610228 1 1.181037 -0.158221 4.758815 1 1.194398 -1.281927 3.377553 1 2.061311 0.263986 3.278845 1 -1.263746 -0.076327 4.723045 1 -2.071585 0.421968 3.227340 1 -1.325430 -1.190589 3.342454 BrDMS 6 0.005599 -0.001246 -0.000412 7 0.005989 -0.001250 1.449965 6 1.303887 -0.018237 2.104742 16 -1.330903 0.536766 2.233966 8 -1.091362 0.391950 3.637147 7 -1.557401 2.201162 1.952349 35 -0.142713 3.351319 2.297192 8 -2.483729 -0.010713 1.573647 1 0.610771 -0.837425 -0.349025 1 -1.005105 -0.140331 -0.371292 1 0.425760 0.924363 -0.407930 1 1.813036 -0.945509 1.839525 1 1.920905 0.828168 1.794897 1 1.170671 0.009317 3.179899 1 -1.853760 2.332691 0.993736 BrDMS- 7 0.265481 0.329418 0.521057 16 0.008724 -0.907189 1.498821 8 1.233535 -1.687494 1.429253 8 -1.258233 -1.611010 1.360151 7 -0.031400 -0.389648 3.151633 35 -1.226800 1.442484 0.310986 6 -1.292307 0.059320 3.690601 6 1.098272 0.413587 3.547467 1 1.178890 0.404653 4.639079 1 2.008525 -0.011610 3.132238 1 1.018319 1.458405 3.214198 1 -1.281978 -0.072862 4.778834 1 -1.503322 1.116169 3.477538 1 -2.093898 -0.544223 3.275810 structure G 6 -0.135943 -0.009766 0.024803 7 -0.060978 0.027191 1.472913 6 1.267745 0.269868 1.990505 16 -1.292478 0.873425 2.299874 8 -1.234305 0.445685 3.690167 8 -2.490261 0.593574 1.540256 7 -0.946935 2.529143 2.256848 8 -0.500075 2.983963 1.069958 1 0.398825 -0.899674 -0.329742 1 -1.176027 -0.088022 -0.274386 1 0.289678 0.887826 -0.430547 1 1.935495 -0.516075 1.627102 1 1.663018 1.243435 1.675480 1 1.250866 0.218122 3.077141 1 -0.246673 2.619879 3.000830 BrUDMH (with 1 explicit water molecule) 6 0.004999 0.138499 -0.007323 7 0.007675 0.052990 1.449167 7 1.044730 0.279304 2.144579 35 2.659547 -1.551440 1.820133 6 -1.013337 -0.777020 2.065147 8 3.174524 1.286429 0.231567 1 -0.975959 -0.628368 3.138096 1 -0.796547 -1.823753 1.837569 1 -1.990923 -0.510364 1.672475 1 -1.005704 0.323290 -0.360146 1 0.671100 0.934949 -0.323324 1 0.372444 -0.811479 -0.403833 1 1.711642 0.816568 1.585657 1 3.422077 0.382355 0.480301 1 3.933939 1.822745 0.457300 structure B (with 5 explicit water molecules) 6 -1.991106 2.613783 0.770999 7 -2.462625 2.145612 -0.527742 16 -1.944889 3.119681 -1.877068 8 -2.324519 2.271273 -3.040672 6 -3.894990 1.884816 -0.549511 8 -0.475867 3.227036 -1.684835 7 -2.646365 5.502258 -2.453808 8 -1.729267 5.981813 -2.887880 8 -2.684679 3.791146 -5.425444 35 -3.105750 6.327904 -0.206099 8 0.112264 0.642626 -3.227414 8 -1.073189 -0.606012 -0.802336 8 1.780517 4.389120 2.094692 8 0.350166 5.498090 -0.104379 1 -4.188189 1.545851 -1.538966 1 -4.107112 1.085952 0.162339 1 -4.487724 2.764388 -0.272015 1 -0.926466 2.819305 0.722420 1 -2.515117 3.510091 1.114510 1 -2.148808 1.810783 1.492714 1 -0.781955 0.957549 -3.414746 1 0.456005 1.381750 -2.716153 1 -0.515478 5.879874 0.080710 1 0.152113 4.753635 -0.692395 1 -2.641639 3.223717 -4.639253 1 -1.815682 3.702505 -5.813319 1 1.815670 3.473100 1.824907 1 1.294192 4.824808 1.373880 1 -1.536754 0.233767 -0.694544 1 -0.562076 -0.446879 -1.605811 structure C (with 5 explicit water molecules) 6 -0.396279 -0.172655 0.183298 7 -0.013620 0.003358 1.572650 7 2.101996 -0.070098 1.882552 35 2.922645 -1.556743 -0.008106 6 -0.538977 -0.988876 2.477828 16 -0.264279 1.736174 2.228133 8 -1.741926 1.792808 2.439613 8 0.141542 2.532779 1.037292 8 2.269457 -0.571387 2.873082 8 -2.654422 4.501871 2.018329 8 -2.120407 3.460515 -0.705072 8 2.832352 2.315113 -0.211455 8 -3.707107 1.166706 0.276942 8 0.855219 -4.059821 1.046137 1 -0.133345 -0.830081 3.479373 1 -1.627626 -0.919817 2.547999 1 -0.260590 -1.987844 2.139049 1 0.072028 0.600137 -0.419814 1 -0.042888 -1.142148 -0.161906 1 -1.481404 -0.106405 0.064997 1 -2.462186 3.578571 2.249806 1 -1.800988 4.928625 2.093013 1 1.541176 -3.428555 0.779902 1 0.382442 -4.228769 0.232299 1 -3.212724 1.266774 1.098463 1 -3.318643 1.864429 -0.268227 1 1.965754 2.427699 0.199353 1 2.917157 1.367423 -0.335430 1 -1.294537 3.121172 -0.334554 1 -2.476255 3.970109 0.033925 structure F (with 3 explicit water molecules) 6 -0.365980 0.158780 0.276140 7 -0.204678 -0.237365 1.669135 6 1.094395 0.004149 2.285363 16 -1.329066 -1.120184 2.445405 8 -2.601772 -0.962505 1.765139 8 -1.211890 -0.920891 3.873998 7 -0.822072 -3.010997 2.060361 8 -0.485607 -3.568953 3.013154 8 -4.259739 1.264356 2.562385 8 -1.946464 2.161812 3.943756 8 -0.081906 3.028672 2.023432 1 1.873440 -0.556143 1.763941 1 -0.018324 3.980505 2.074214 1 -0.743844 2.785963 2.695025 1 -1.371248 -0.069426 -0.059045 1 -0.205461 1.234223 0.211554 1 0.355969 -0.364011 -0.353975 1 1.304026 1.071044 2.229163 1 1.071522 -0.292604 3.328653 1 -2.804526 1.961447 3.537046 1 -1.666213 1.325572 4.321899 1 -3.868886 0.451485 2.216624 1 -5.065888 0.994577 3.000314 structure D (with 3 explicit water molecules) 1 -0.094379 0.029889 0.017610 6 -0.051418 0.002499 1.110891 1 0.998950 -0.051218 1.403597 1 -0.545250 -0.919405 1.451449 7 -0.644695 1.199170 1.651291 6 -2.057248 1.324420 1.368248 1 -2.195520 1.444798 0.289236 1 -2.648132 0.462491 1.702022 1 -2.439166 2.215607 1.862485 16 -0.172835 1.451592 3.332867 8 -0.760225 0.282339 4.093524 8 -0.929188 2.700232 3.676864 1 -2.677908 2.646213 4.460921 1 -1.029933 0.883011 5.922133 8 -1.130857 1.480289 6.684509 1 -0.804863 2.303638 6.316463 8 -3.441805 2.516974 5.051119 1 -3.010854 2.156575 5.834120 1 -3.825981 0.559222 4.431016 1 -2.636375 -0.292309 4.123750 8 -3.601138 -0.351031 4.202144 NDMA 6 0.001663 0.062809 -0.017390 7 0.085963 0.290123 1.402273 6 1.338005 0.101123 2.098503 7 -1.039117 0.675996 2.008255 8 -0.970963 0.867744 3.198339 1 1.173230 0.324024 3.148084 1 1.678228 -0.929373 1.988979 1 2.098871 0.769984 1.694243 1 -1.019335 0.261482 -0.330025 1 0.681068 0.726572 -0.555087 1 0.260106 -0.969854 -0.258425 ----------------------------------------------------------------------- Optimized Cartesian Coordinates (Angstroms) of all transition state structures. TS-pathway-b (with 3 explicit water molecules) 6 0.000424 0.000546 -0.000239 7 0.000518 0.002266 1.450247 16 1.482805 -0.000938 2.188904 8 1.191654 0.042483 3.615910 6 -1.136011 -0.644480 2.081513 7 2.300676 -1.396658 1.929205 35 1.419923 -3.304103 2.143257 8 0.747526 -5.213655 2.464846 8 2.243943 1.064138 1.585540 8 1.672879 -5.643567 4.774670 8 2.413503 -3.536472 5.812864 8 3.095333 -1.568924 4.621350 1 -1.025511 -0.608679 3.159235 1 -2.036064 -0.092287 1.807824 1 -1.249111 -1.684350 1.764481 1 0.819122 0.610367 -0.369988 1 0.079405 -1.011499 -0.413205 1 -0.933686 0.442456 -0.345711 1 2.760224 -1.326707 1.030682 1 3.186707 -1.703706 3.652322 1 2.747386 -2.589895 5.188444 1 2.375182 -0.900946 4.614559 1 2.985580 -3.711770 6.558787 1 2.128730 -4.451777 5.336856 1 1.233744 -5.505069 3.851190 1 2.332211 -6.324917 4.650800 1 -0.202857 -5.201492 2.347595 TS-pathway-g (with 1 explicit water molecule) 6 -0.053502 -0.159907 -0.064134 7 0.017475 0.006106 1.379985 6 1.342024 0.107354 1.980357 16 -1.405871 -0.316443 2.402636 7 -1.151340 1.208698 1.905809 8 -2.391175 -1.014015 1.649907 8 -0.956240 -0.733921 3.689363 35 -3.110399 1.947039 3.551699 1 0.399063 0.705238 -0.546385 1 0.488808 -1.064317 -0.339969 1 -1.089494 -0.251666 -0.369359 1 1.888439 -0.813258 1.774232 1 1.870030 0.952594 1.540677 1 1.255824 0.245379 3.052616 1 -0.638800 1.724278 2.648267 8 0.040734 2.529889 4.155368 1 -0.891051 2.485069 4.436107 1 0.236951 3.466779 4.136186 TS-pathway-j 6 -0.044998 -0.111194 -0.023199 7 0.007729 0.064202 1.412357 6 1.332540 0.035783 2.000488 16 -1.213934 0.892712 2.180430 8 -2.444633 0.463373 1.563161 8 -0.995721 0.705285 3.589425 7 -1.063654 2.586910 1.945258 8 0.472577 2.907567 2.257539 8 0.573607 3.771525 3.291207 8 0.514411 5.045901 2.913797 35 -1.555904 3.138447 0.192791 1 1.259339 0.196053 3.069927 1 1.769302 -0.950118 1.817647 1 1.984530 0.803061 1.576031 1 -1.077405 -0.109747 -0.356500 1 0.502392 0.673372 -0.554753 1 0.400730 -1.078292 -0.271027 TS-pathway-n 6 0.012889 -0.022075 -0.009199 7 0.015582 -0.003782 1.435547 6 1.268626 -0.007831 2.136257 16 -1.475769 -0.645271 2.340311 8 -0.900999 -1.349430 3.481385 8 -2.205872 -1.403644 1.333329 7 -1.040110 1.578757 2.010261 8 -0.512791 2.125234 2.855609 1 1.334135 0.873442 2.791343 1 1.352363 -0.887584 2.772854 1 2.097049 0.026786 1.432078 1 -1.011130 0.001208 -0.370722 1 0.556512 0.842697 -0.395525 1 0.481703 -0.934386 -0.382980 ----------------------------------------------------------------------- Cartesian Coordinates (Angstroms) of structures approximately at the top of the electronic energy barrier Step k. Barrier structure. 8 0.000000 0.000000 0.000000 7 0.000000 0.000000 1.120288 7 3.132218 0.000000 2.959781 16 3.020075 1.564949 2.124385 8 2.731911 0.762888 -1.257795 1 3.279077 0.986523 -0.481193 8 4.110165 1.420040 1.104839 8 3.407147 2.504292 3.223440 1 2.685398 1.582920 -1.745649 8 1.732721 2.888812 6.878752 1 1.418859 3.202639 6.014884 1 2.630222 2.610476 6.700046 1 2.264081 0.764234 4.698989 6 2.201705 -0.116276 4.065175 1 1.157576 -0.243538 3.744894 1 2.474514 -0.983329 4.670282 1 2.130849 -1.385611 1.675787 6 3.125577 -1.149647 2.082271 1 3.813741 -0.985223 1.258067 1 3.469066 -2.023362 2.640984 8 1.074996 3.709259 4.213304 1 0.393476 3.203842 3.768094 1 1.907488 3.381808 3.822464 35 -1.467119 1.371965 2.025210 8 6.341132 2.363475 2.757175 1 5.564987 2.685420 3.231379 1 5.908628 1.992759 1.976212 8 5.952873 -0.232196 4.135499 1 5.041747 -0.163889 3.817892 1 6.339854 0.577639 3.778255 Step l. Barrier structure. 6 0.000000 0.000000 0.000000 7 0.000000 0.000000 1.451302 7 1.824372 0.000000 2.025742 8 1.863470 -0.223892 3.132096 16 -0.625336 1.673997 2.204518 8 -2.085403 1.583547 1.940388 6 -0.673082 -1.112431 2.084848 8 0.039078 2.631715 1.283249 35 2.754743 -2.249327 0.726621 8 -3.269949 4.212503 1.614703 8 -1.700372 3.816489 -0.857266 8 -3.227047 1.294310 -0.876168 8 2.891368 3.096841 1.575904 8 0.364107 -4.572852 1.291067 1 -0.440231 -1.113375 3.151750 1 -1.754130 -1.011168 1.974555 1 -0.341331 -2.053233 1.650596 1 0.571993 0.854789 -0.353014 1 0.475706 -0.914431 -0.348743 1 -1.018136 0.075482 -0.386256 1 -2.997251 3.295223 1.772113 1 -2.680013 4.724558 2.166854 1 1.127341 -3.974309 1.230767 1 0.185737 -4.784464 0.375946 1 -3.061911 1.239007 0.069738 1 -2.764421 2.110607 -1.111535 1 1.933553 3.024099 1.462197 1 3.236428 2.335218 1.110965 1 -0.992499 3.449475 -0.312491 1 -2.319032 4.148240 -0.193868 Step m. Barrier structure. 35 0.000000 0.000000 0.000000 7 0.000000 0.000000 6.630000 16 1.765114 0.000000 5.753137 7 1.449738 -0.159857 4.172158 8 -0.220716 -1.030785 7.117531 8 2.458886 -1.184382 6.237883 8 2.296619 1.310883 6.023414 6 0.991755 1.005079 3.408848 6 1.148090 -1.477999 3.614276 1 1.675687 -2.249654 4.161795 1 1.452362 -1.469993 2.569340 1 0.070362 -1.630569 3.643268 1 1.032101 1.890175 4.034328 1 1.638426 1.135979 2.543980 1 -0.016567 0.835930 3.040386 8 -2.188883 -1.089860 2.324557 1 -1.473395 -0.957639 1.685094 1 -2.796719 -0.399031 2.035341 1 -2.034415 0.971543 0.268593 8 -2.946091 1.256257 0.497569 1 -3.471367 0.846200 -0.188695 8 2.015136 0.850573 10.117538 1 2.629439 0.166465 9.826202 1 1.426575 0.440871 10.746480 8 3.375707 -1.359330 8.876396 1 3.099348 -1.360045 7.946468 1 4.164750 -1.895891 8.942307 1 2.316290 -2.390073 10.187823 8 2.129992 -3.110370 10.803754 1 1.211756 -3.328442 10.651414 Step o. Barrier structure. 7 0.000000 0.000000 0.000000 16 0.000000 0.000000 4.467896 8 1.309747 0.000000 3.720375 8 -0.707422 -1.306060 4.302076 35 -0.796719 1.503916 -1.528599 8 0.815578 -0.637039 -0.394108 8 2.773657 2.131610 -0.966090 1 1.940898 2.179718 -1.439673 1 2.495927 1.992935 -0.050613 8 1.455756 1.657208 1.558657 1 0.778739 2.313024 1.718922 1 1.449569 1.084458 2.356872 8 -0.607591 -2.461059 1.612786 1 0.240656 -2.830134 1.876995 1 -0.876509 -2.006132 2.423317 8 1.689459 -2.883780 3.604603 1 0.820430 -2.805257 4.019054 1 1.899711 -1.943554 3.498474 8 2.443858 -2.540767 6.513175 1 1.852362 -1.781293 6.399653 1 2.469547 -2.903208 5.621352 7 0.608281 -0.164694 6.146156 6 1.454044 0.954590 6.516025 1 2.239306 1.075794 5.774586 1 0.899855 1.901576 6.608029 1 1.923070 0.744396 7.479353 6 -0.478431 -0.366517 7.085971 1 -1.111855 0.525563 7.210021 1 -1.097774 -1.193670 6.749828 1 -0.062415 -0.622260 8.062666 Step p. Barrier structure. 1 7 0 0.000000 0.000000 0.000000 2 7 0 0.000000 0.000000 4.239455 3 8 0 0.924614 0.000000 -0.617457 4 35 0 -1.842516 -0.847502 -1.089090 5 8 0 -0.041146 -1.863579 1.981802 6 1 0 -0.915077 -1.872393 1.589094 7 1 0 -0.078576 -1.169290 2.668212 8 16 0 0.513240 1.644992 3.770335 9 8 0 -0.686758 2.094841 2.980630 10 8 0 0.575322 2.397008 5.068418 11 6 0 -1.310910 -0.054144 4.861078 12 1 0 -1.644025 -1.093935 4.898695 13 1 0 -2.016844 0.513458 4.258374 14 1 0 -1.316582 0.346247 5.881746 15 1 0 0.819335 -1.714063 5.098795 16 6 0 1.027400 -0.643866 5.034932 17 1 0 1.996727 -0.519605 4.550745 18 1 0 1.094469 -0.235839 6.050925 19 8 0 -0.732576 2.376405 0.222987 20 1 0 -0.697863 2.329988 1.199999 21 1 0 -1.639289 2.155209 0.009114 22 8 0 -0.078242 5.293948 5.261461 23 1 0 0.392195 4.459853 5.134486 24 1 0 -0.902415 5.129255 4.782712 25 1 0 -1.118737 4.065974 6.895088 26 8 0 -1.435834 3.158046 6.931798 27 1 0 -0.773640 2.710884 6.377789 28 8 0 -2.517950 3.943969 4.252625 29 1 0 -1.963449 3.327126 3.748865 30 1 0 -2.460981 3.597215 5.151832