Theoretical Investigation of Loratadine Reactivity in Order to Understand Its Degradation

Theoretical investigation of loratadine reactivity in order to understand its degradation properties: DFT and MD study

Stevan Armaković1, Sanja J. Armaković2, Biljana F. Abramović2

1University of Novi Sad, Faculty of Sciences, Department of Physics, Trg D. Obradovića 4, 21000 Novi Sad, Serbia

2University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad, Serbia

* Corresponding Author: Stevan Armaković; Tel: +381 21 485 2796; Fax: +381 21 455318; E-mail:[email protected]

Supplementary materials

1 Fig. S1. Changes of energy in the last ns of the MD simulation

Fig. S2. IR spectra of LOR

Fig. S3. IR spectra of LOR compound 1

2 Fig. S4. IR spectra of LOR compound 2

Fig. S5. IR spectra of LOR compound 3

3 Fig. S6. IR spectra of LOR compound 4

Fig. S7. IR spectra of LOR compound 5

4 Fig. S8. IR spectra of LOR compound 6

Fig. S9. IR spectra of LOR compound 7

5 Table S1. LOR 13C NMR chemical shifts [ppm] [ppm] Atom #   Theo Exp C2 154.64 NA* C4 63.03 62.43 C5 14.59 14.78 C7 45.57 45.50 C8 32.17 31.22 C9 145.73 NA C10 141.42 NA C11 140.13 NA C12 134.10 146.73 C13 126.42 126.82 C14 131.09 NA C16 132.30 130.15 C17 143.28 NA C18 34.62 32.57 C19 31.13 31.88 C20 136.43 NA C21 137.96 139.29 C22 123.40 123.84 C23 149.22 131.33 13 C25 165.19 NA Fig. S10. Correlation between measured and calculated C C26 32.48 31.22 NMR NMR chemical shifts C27 45.69 45.50 *Not available Table S2. LOR 1H NMR chemical shifts [ppm] [ppm] Atom #   Theo Exp H28 4.69 4.12 H29 3.93 4.12 H30 1.09 1.26 H31 1.31 1.26 H32 1.52 1.26 H33 4.10 3.78 H34 2.66 NA H35 2.28 2.21 H36 2.34 2.34 H37 7.09 8.32 H38 7.06 7.16 H39 7.18 7.21 H40 3.46 NA H41 3.72 NA H42 2.82 NA H43 3.28 NA H44 7.83 7.63 H45 7.29 7.24 H46 8.43 7.11 Fig. S11. Correlation between measured and calculated 1H H47 2.50 2.39 NMR chemical shifts H48 2.63 2.39 H49 4.20 3.78 H50 2.78 3.21

6 Table S3. Compound 1 13C NMR and 1H NMR chemical shifts Atom #  [ppm] Atom #  [ppm] C1 145.1 H26 7.10 C2 144.29 H27 7.06 C3 130.77 H28 7.20 C4 128.87 H29 2.26 C5 127.74 H30 3.43 C6 131.20 H31 3.86 C7 141.45 H32 3.29 C8 160.32 H33 7.88 C9 138.64 H34 7.30 C10 31.82 H35 8.42 C11 35.01 H36 2.47 C12 141.67 H37 2.93 C13 122.95 H38 2.25 C15 147.95 H39 2.36 C16 146.90 H40 4.06 C17 31.80 H41 2.96 Fig. S12. Structure and atom numeration of C18 32.93 H42 2.65 compound 1 C19 46.67 H43 4.12 C21 46.36 H44 5.72 C22 153.59

Table S4. Compound 2 13C NMR and 1H NMR chemical shifts Atom #  [ppm] Atom #  [ppm] C1 145.10 H26 7.10 C2 144.29 H27 7.06 C3 130.77 H28 7.20 C4 128.87 H29 2.26 C5 127.74 H30 3.43 C6 131.20 H31 3.86 C7 141.45 H32 3.29 C8 160.32 H33 7.88 C9 138.64 H34 7.30 C10 31.82 H35 8.42 C11 35.01 H36 2.47 C12 141.67 H37 2.93 C13 122.95 H38 2.25 C15 147.95 H39 2.36 C16 146.90 H40 4.06 C17 31.80 H41 2.96 C18 32.93 H42 2.65 Fig. S13. Structure and atom numeration of C19 46.67 H43 4.12 compound 2 C21 46.36 H44 5.72 C22 153.59

7 Table S5. Compound 3 13C NMR and 1H NMR chemical shifts Atom #  [ppm] Atom #  [ppm] C1 145.46 H27 6.96 C2 141.52 H28 7.15 C3 129.25 H29 7.37 C4 128.00 H30 7.23 C5 127.78 H31 2.12 C6 128.15 H32 2.74 C7 142.41 H33 4.12 C8 160.62 H34 3.94 C9 137.63 H35 8.18 C10 31.45 H36 7.25 C11 35.45 H37 8.28 C12 140.99 H38 2.50 C13 121.67 H39 2.78 C15 146.45 H40 2.46 C16 145.44 H41 2.47 C17 31.81 H42 4.24 C18 34.05 H43 2.85 C19 45.69 H44 2.60 Fig. S14. Structure and atom numeration of C21 45.67 H45 4.05 compound 3 C22 154.91 H46 3.84 C24 63.81 H47 3.93 C25 13.29 H48 1.21 H49 1.54 H50 1.58

Table S6. Compound 4 13C NMR and 1H NMR chemical shifts Atom #  [ppm] Atom #  [ppm] C1 146.29 H25 7.26 C2 146.49 H26 7.45 C3 131.92 H27 7.40 C4 129.39 H28 2.78 C5 129.13 H29 4.23 C6 132.18 H30 3.08 C7 142.37 H31 2.59 C8 159.31 H32 7.08 C9 139.91 H33 7.12 C10 32.16 H34 8.46 C11 34.78 H35 2.36 C12 141.66 H36 2.88 C13 122.12 H37 2.44 C15 149.14 H38 2.32 C16 147.42 H39 3.49 C17 32.61 H40 3.23 C18 33.84 H41 2.64 Fig. S15. Structure and atom numeration of C19 46.65 H42 4.30 compound 4 C21 40.86 H43 8.01 C22 161.43

8 Table S7. Compound 5 13C NMR and 1H NMR chemical shifts Atom #  [ppm] Atom #  [ppm] C1 140.53 H23 7.09 C2 143.50 H24 6.85 C3 134.69 H25 7.14 C4 131.70 H26 3.15 C5 127.62 H27 3.22 C6 130.49 H28 3.05 C7 140.04 H29 3.04 C8 164.68 H30 8.05 C9 136.45 H31 7.38 C10 32.61 H32 8.35 C11 32.14 H33 2.18 C12 136.75 H34 2.13 C13 121.55 H35 2.34 C15 146.91 H36 2.60 C16 149.16 H37 2.37 Fig. S16. Structure and atom numeration of C17 33.82 H38 2.88 C18 35.90 H39 1.20 compound 5 C19 48.51 H40 2.90 C21 49.93 H41 2.50

Table S9. Compound 6 13C NMR and 1H NMR chemical shifts Atom #  [ppm] Atom #  [ppm] C1 137.01 H28 6.91 C2 143.85 H29 6.67 C3 130.66 H30 6.56 C4 114.19 H31 2.21 C5 111.89 H32 3.33 C6 156.01 H33 3.78 C7 142.34 H34 3.31 C8 161.15 H35 7.85 C9 137.77 H36 7.28 C10 32.09 H37 8.33 C11 35.31 H38 2.42 C12 141.28 H39 2.90 C13 121.84 H40 2.34 C15 147.23 H41 2.27 C16 145.95 H42 4.26 C17 31.87 H43 2.91 C18 33.69 H44 2.64 C19 45.98 H45 4.04 C21 45.88 H46 3.89 Fig. S17. Structure and atom numeration of C22 154.72 H47 3.98 compound 6 C24 63.76 H48 1.28 C25 13.32 H49 1.50 H50 1.53 H51 5.09

9 Table S10. Compound 7 13C NMR and 1H NMR chemical shifts Atom #  [ppm] Atom #  [ppm] C1 140.84 H22 7.09 C2 140.86 H23 7.26 C3 132.38 H24 7.25 C4 131.95 H25 7.31 C5 126.07 H26 3.48 C6 127.33 H27 3.07 C7 140.10 H28 2.56 C8 166.87 H29 3.83 C9 140.04 H30 7.66 C10 33.71 H31 7.27 C11 31.23 H32 8.55 C12 138.59 H33 2.22 C13 122.69 H34 2.17 C15 149.10 H35 2.30 Fig. S18. Structure and atom numeration of C16 146.86 H36 2.57 C17 34.32 H37 2.51 compound 7 C18 35.53 H38 2.97 C19 48.90 H39 1.18 C21 49.86 H40 2.98 H41 2.63

References