1/sec - Royal Society of Chemistry

Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is (c) The Royal Society of Chemistry 2011

Measurement 1

Measurement 2

Measurement 3

Experiment number

pH

k (1/sec)

Temp

k (1/sec)

Temp

k (1/sec)

Temp

Ea/R

lnA

Ea (kJ/mol)

Predicted half-life at 25oC (days)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

7.4 7.4 7.4 8 4 1 1 1 8 7.4 1 1 1 1 8 1 4 8 4 1 6 10 4 8 6 7.4 1 4 1 6 8

0.0000337 0.0000869 0.00195 0.003156 0.0007406 0.001458 0.00139 0.001375 0.000408 0.00006887 0.00251 0.003242 0.001203 0.0006681 0.0000644 0.00018 0 0002605 0.0002605 0.0001245 0.00001643 0.00004036 0.006 0.0000867 0.00002098 0.00001816 0.0005961 0.0001846 0.002672 0.00001547 0.00004066 0.000002343 0.000003916

70 70 60 90 60 70 80 90 90 90 80 90 90 90 90 80 90 90 90 90 90 90 90 90 81 90 90 90 90 90 90

0.00000906 0.000024 0.000239 0.0001387 0.00002624 0.0006419 0.000548 0.0006536 0.000129 0.0000303 0.001071 0.001523 0.000566 0.0002686 0.00001879 0.00008885 0 00000484 0.00000484 0.0000518 0.00000531 0.00003256 0.001916 0.0000368 0.00001153 0.000007311 0.0003535 0.000114 0.0009117 0.000007354 0.000021 0.000001069 0.000001576

60 60 50 80 51 60 70 80 81 81 70 80 80 80 80 70 50 80 80 80 80 80 81 81 70 81 80 80 80 80 80

0.00000237 0.00000611 0.00008279 0.0000425 0.00000796 0.0002671 0.0002369 0.000266 0.000008296 0.0000158 0.0004959 0.0007178 0.00025 0.00007876 0.000006166 0.00004274 0 000001146 0.000001146 0.00001781 0.000001604 0.00001343 0.000587 0.00001132 0.00000507 0.00000254 0.0001806 0.00006273 0.0003427 0.00000393 0.000009979 6.199E-07 0.000000825

50 50 40 69 40 50 60 70 60 71 61 70 70 70 70 60 37 70 70 70 70 70 70 70 62 71 71 70 70 70 70

14949 14955 19467 11654 11552 9781 10302 10010 16210 9543 10081 9423 9516 13017 14508 8554 11565 12124 14497 6895 14230 12416 8703 12009 7404 6790 12979 8515 8755 8268 9685

33 34 52 24 25 22 22 20 37 16 22 20 19 29 30 16 23 24 29 9 34 25 13 22 14 11 30 12 14 10 14

124 124 162 97 96 81 86 83 135 79 84 78 79 108 121 71 96 101 121 57 118 103 72 100 62 56 108 71 73 69 81

173 157 6.3 28.8 6.78 0.41 1.34 2.47 341 36.5 0.62 0.73 2.1 29.7 809 3.97 32 2 32.2 91.2 2939 11.2 7.4 164 73.5 645 0.66 2.61 7.8 88.5 37.5 513 724

Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is (c) The Royal Society of Chemistry 2011

Measurement 1

Measurement 2

Measurement 3

Experiment number

pH

k (1/sec)

Temp

k (1/sec)

Temp

k (1/sec)

Temp

Ea/R

lnA

Ea (kJ/mol)

Predicted half-life at 25oC (days)

32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62

10 6 4 8 4 8 7.4 7.4 1 10 8 7.4 1 1 7.4 1 10 1 4 10 1 4 1 10 1 4 6 8 10 4 6

0.0000104 0.0000118 0.00000879 0.00001096 0.00001343 0.00001969 0.0001734 0.000138 0.000208 0.0000728 0.000023 0.000161 0.0002954 0.000298 0.0000421 0.000132 0 0000767 0.0000767 0.0000291 0.00002 0.00000745 0.0000362 0.0000244 0.000208 0.0000728 0.0000616 0.0000445 0.0000364 0.0000321 0.0000321 0.0000879 0.000077

90 90 90 90 90 90 90 90 80 88 90 90 80 80 94 90 90 90 90 90 90 90 80 88 70 70 70 70 70 90 90

0.000005169 0.000006989 0.000003819 0.00000507 0.000004723 0.000006692 0.00005538 0.0000388 0.0000628 0.0000256 0.0000103 0.0000546 0.0000937 0.000103 0.00002726 0.0000329 0 00002 0.00002 0.00000396 0.00000235 0.00000369 0.00000916 0.00000573 0.0000628 0.0000256 0.0000167 0.0000121 0.0000131 0.00001407 0.00000206 0.000038 0.0000218

80 80 80 80 80 80 80 80 70 78 81 80 70 70 90 80 80 80 80 80 80 80 70 78 60 60 60 60 60 80 80

0.000002519 0.00000232 0.000002514 0.00000291 0.00000277 0.000004029 0.00000822 0.0000112 0.0000114 0.000014 0.000003776 0.0000214 0.0000283 0.0000292 0.000005655 0.00000753 0 00000484 0.00000484 0.0000012 0.00000063 0.00000175 0.00000186 0.00000123 0.0000114 0.000014 0.000009 0.00000411 0.00000514 0.00000469 0.00000612 0.0000291 0.000016

70 70 70 70 70 70 60 70 60 68 71 70 60 60 80 70 70 70 70 70 70 70 60 68 50 50 50 50 50 70 70

8455 8845 7778 8244 9783 9850 12122 15642 17107 12108 11741 12562 13797 13669 18913 17870 17212 20118 21819 8151 18395 18507 17107 10128 10406 12886 10377 10375 8951 6808 9668

13 13 10 11 15 16 24 24 40 18 21 25 31 30 42 41 38 45 49 13 40 40 40 18 20 27 20 19 15 9 14

70 74 65 69 81 82 101 130 142 101 98 104 115 114 157 149 143 167 181 68 153 154 142 84 87 107 86 86 74 57 80

156 239 105 108 233 167 73 708 273 45 417 14.8 36.8 33.2 27108 2762 3213 52574 212245 253 13319 21607 273 45 14.4 1322 23.9 23.5 11.5 6 41

Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is (c) The Royal Society of Chemistry 2011

Measurement 1

Measurement 2

Measurement 3

Experiment number

pH

k (1/sec)

Temp

k (1/sec)

Temp

k (1/sec)

Temp

Ea/R

lnA

Ea (kJ/mol)

Predicted half-life at 25oC (days)

63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93

8 10 4 1 4 6 8 10 1 4 6 8 10 4 6 8 10 1 6 8 10 1 8 10 1 4 6 7.4 8 10 1

0.000079 0.000112 0.0000573 0.0000652 0.0000476 0.000048 0.0000493 0.0000494 0.0000427 0.0000837 0.000055 0.000055 0.00006 0.0000233 0.0000213 0.0000246 0 0000474 0.0000474 0.0000232 0.00003586 0.000106 0.0002574 0.0000399 0.00004364 0.000324 0.000139 0.00009 0.000087 0.00006426 0.0000819 0.0000478 0.00045

90 90 89 89 89 89 89 89 89 89 89 89 89 90 90 90 90 90 90 90 90 90 90 70 80 80 80 80 80 80 90

0.000019 0.0000298 0.0000107 0.0000141 0.0000146 0.0000198 0.0000178 0.00002 0.0000232 0.0000219 0.0000199 0.000007 0.000008 0.0000119 0.0000115 0.0000124 0 0000158 0.0000158 0.0000118 0.0000141 0.00004657 0.0001183 0.0000194 0.00001585 0.0001159 0.0000519 0.0000266 0.00002505 0.00001945 0.0000212 0.0000206 0.0001974

80 80 77 77 77 77 77 77 77 77 77 77 77 80 80 80 80 80 80 80 80 80 80 60 70 70 70 70 70 70 80

0.0000109 0.0000158 0.00000223 0.00000112 0.00000138 0.00000334 0.00000512 0.00000521 0.0000069 0.00000481 0.00000566 0.000001346 0.000002 0.00000583 0.000006 0.000006 0 00000495 0.00000495 0.00000481 0.000004217 0.00001875 0.00004445 0.00000607 0.000006464 0.0000423 0.000014 0.00000747 0.000007222 0.00000631 0.00000642 0.00000808 0.0000804

70 70 68 68 68 68 68 68 68 68 68 68 68 70 70 70 70 70 70 70 70 70 70 50 60 60 60 60 60 60 70

12215 12095 19281 23871 20651 15566 13383 13207 10632 17136 13424 22141 20257 8640 7853 8743 14082 9801 13350 10520 10952 11757 11889 11291 13520 14639 14637 13642 14970 10472 10726

24 24 44 56 47 33 27 26 19 38 27 51 46 13 11 13 28 16 26 20 22 22 22 24 29 32 32 29 33 19 22

102 101 160 198 172 129 111 110 88 142 112 184 168 72 65 73 117 81 111 87 91 98 99 94 112 122 122 113 124 87 89

183 117 12571 141855 28240 1445 426 372 92 2312 391 73849 22995 61 42 62 794 121 653 44 22 218 238 3.6 64 187 195 159 253 39 11

Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is (c) The Royal Society of Chemistry 2011

Measurement 1

Measurement 2

Measurement 3

Experiment number

pH

k (1/sec)

Temp

k (1/sec)

Temp

k (1/sec)

Temp

Ea/R

lnA

Ea (kJ/mol)

Predicted half-life at 25oC (days)

94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124

4 6 8 10 3 7.4 1 4 6 8 10 8 10 1 9.2 10 1 7.4 10 10 1 3.1 3.1 7.4 1 9.8 1 1 7.4 1 7.4

0.0000077 0.00000862 0.0000204 0.00065 0.0000825 0.0000929 0.0001782 0.0000099 0.0000118 0.0000142 0.00002463 0.0000535 0.000089 0.000249 0.0000416 0.00077 0 00001419 0.00001419 0.000271 0.00011 0.00001618 0.00002173 0.000196 0.00000853 0.0000127 0.000387 0.00002 0.0000728 0.000285 0.0002315 0.001625 0.0003238

90 90 90 90 90 90 90 90 90 90 90 90 90 91 91 91 94 91 91 91 91 91 91 91 90 91 60 90 90 90 90

0.00000321 0.00000299 0.0000057 0.000265 0.0000231 0.0000244 0.0000482 0.00000281 0.00000426 0.00000492 0.0000117 0.0000208 0.000045 0.0001161 0.000013 0.000295 0 00001052 0.00001052 0.00003864 0.00005 0.00000863 0.00001318 0.0000622 0.00000531 0.00000548 0.00016 0.0000134 0.0000205 0.0001574 0.0001069 0.0008135 0.0001327

80 80 80 80 80 80 80 80 80 80 80 80 80 81 81 81 91 52 80 82 81 81 81 81 78 82 45 80 80 91 81

0.00000165 0.00000147 0.00000207 0.000101 0.00000598 0.00000591 0.0000263 0.00000131 0.000001318 0.00000227 0.00000639 0.00000561 0.0000257 0.0000798 0.0000084 0.0001469 0 000004467 0.000004467 0.0000111 0.0000191 0.000002799 0.000005236 0.000017 0.00000154 0.000001528 0.0000778 0.00000618 0.00000278 0.0000409 0.00003044 0.0003739 0.00000303

70 70 70 70 70 70 70 70 70 70 70 70 70 76 76 76 76 38 70 72 72 72 72 72 69 69 25 63 70 70 37

9644 10977 14225 11583 16350 17164 11874 12616 13671 11405 8380 14029 7712 10101 13899 12703 7219 6608 10817 12050 9687 13231 11670 14341 9531 6584 9216 9156 12631 9153 9671

15 19 28 25 35 38 24 28 27 20 12 39 11 19 28 27 8 10 21 52 16 27 21 28 18 7 18 17 26 19 18

80 91 118 96 136 143 99 105 114 95 70 117 64 84 116 106 60 55 90 100 81 110 97 119 79 55 77 76 105 76 80

352 734 2128 13 1779 2579 64 1721 2451 563 52 654 9.5 15 951 23 57 1.6 49 682 121 182 972 3750 6.2 21.4 2.9 6.8 66 1.3 1

Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is (c) The Royal Society of Chemistry 2011

Measurement 1

Measurement 2

Measurement 3

Experiment number

pH

k (1/sec)

Temp

k (1/sec)

Temp

k (1/sec)

Temp

Ea/R

lnA

Ea (kJ/mol)

Predicted half-life at 25oC (days)

125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155

7.4 1 1 5 1 3 7.4 9.4 7.4 7.4 1 9.8 5.1 7.4 9.8 8.2 74 7.4 1 1 7.4 1 7.4 10 1 6 8 10 1 8 10 1

0.000208 0.00003206 0.000877 0.000358 0.0000724 0.00009977 0.00097 0.000024 0.00011 0.00097 0.000032 0.000918 0.00002388 0.000006577 0.0006 0.0000635 0 00097 0.00097 0.0000272 0.000647 0.0000644 0.0000707 0.0000151 0.000108 0.000206 0.00003922 0.00025 0.000463 0.000354 0.000199 0.000458 0.0000908

70 90 90 90 90 91 91 90 70 91 90 92 91 91 92 92 91 91 91 91 91 90 90 89 89 89 89 80 89 89 89

0.0000607 0.0000214 0.000414 0.000202 0.0000442 0.0000391 0.0005 0.0000158 0.00003459 0.0005 0.0000215 0.000468 0.00001 0.00000354 0.000295 0.000026 0 0005 0.0005 0.00001524 0.000241 0.0000302 0.0000354 0.00000875 0.00007047 0.0001027 0.00001468 0.0001269 0.000248 0.0002211 0.00008359 0.0001442 0.0000692

61 82 81 82 82 82 81 83 61 81 82 84 83 86 84 82 81 82 82 81 82 81 83 80 80 80 80 70 80 80 80

0.0000155 0.000006893 0.000209 0.0000982 0.0000183 0.00001151 0.00021 0.00000873 0.00000699 0.00021 0.00000683 0.000192 0.00000436 0.000001549 0.0001419 0.00001138 0 00021 0.00021 0.00000246 0.0000722 0.00000948 0.00000582 0.0000042 0.0000529 0.00002 0.000003745 0.00002231 0.0000482 0.0000535 0.00001314 0.0000415 0.00001529

50 73 71 73 71 72 70 70 50 70 73 74 74 80 76 73 70 60 71 71 60 73 75 60 60 60 60 60 60 60 60

14549 11377 9313 9596 9009 13983 9213 6007 15562 9213 11377 10914 12727 16489 11479 11361 9213 9622 14092 12469 9901 9074 8024 9397 9607 9908 9379 10834 10981 9309 7349

34 21 19 18 15 29 18 5 36 18 21 23 24 33 24 21 18 16 31 27 18 14 13 17 16 19 18 23 22 18 11

121 95 77 80 75 116 77 50 129 77 95 91 106 137 95 94 77 80 117 104 82 75 67 78 80 82 78 90 91 77 61

24 213 62 7.2 25 393 2.2 13 66 2.2 213 7 790 27591 15 134 22 2.2 96 63 223 45 123 9 10 74 12 4.6 5.8 29 5.5 6.2

Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is (c) The Royal Society of Chemistry 2011

Measurement 1

Measurement 2

Measurement 3

Experiment number

pH

k (1/sec)

Temp

k (1/sec)

Temp

k (1/sec)

Temp

Ea/R

lnA

Ea (kJ/mol)

Predicted half-life at 25oC (days)

156 157 158 159 160 161 162 163 164 165 166

4 6 8 10 1 4 6 8 10 1 10

0.0000108 0.0000156 0.0000864 0.000385 0.0000899 0.0000105 0.0000181 0.0000759 0.000419 0.00019 0.000177

89 89 89 89 89 89 89 89 80 81 81

0.00000427 0.00000716 0.0000281 0.0004 0.0000701 0.0000048 0.00000692 0.0000318 0.000161 0.00007 0.0000963

80 80 80 80 80 80 80 80 70 71 71

0.00000322 0.00000139 0.0000127 0.0000881 0.00001511 0.00000302 0.00000142 0.0000122 0.0000531 0.000043 0.00002242

70 70 70 60 60 70 70 70 60 61 61

7478 15482 12023 7189 7403 7787 16226 11564 11867 8543 11854

9 32 23 12 11 10 34 22 26 15 25

62 129 100 60 62 65 135 96 99 71 99

74 4688 133 1.3 6.4 86 6597 106 10 4 22