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, BiljanaF. 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:
Supplementary materials
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 compound1
Fig. S4. IR spectra of LOR compound2
Fig. S5. IR spectra of LOR compound3
Fig. S6. IR spectra of LOR compound4
Fig. S7. IR spectra of LOR compound5
Fig. S8. IR spectra of LOR compound6
Fig. S9. IR spectra of LOR compound7
Table S1. LOR 13C NMR chemical shiftsAtom # / [ppm]
Theo / [ppm]
Exp [1-4]
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
C25 / 165.19 / NA
C26 / 32.48 / 31.22
C27 / 45.69 / 45.50
*Not available /
Fig. S10. Correlation between measured and calculated 13C NMR NMR chemical shifts
Table S2. LOR 1H NMR chemical shifts
Atom # / [ppm]
Theo / [ppm]
Exp[1-4]
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
H47 / 2.50 / 2.39
H48 / 2.63 / 2.39
H49 / 4.20 / 3.78
H50 / 2.78 / 3.21
/
Fig.S11. Correlation between measured and calculated 1H NMR chemical shifts
Table S3. Compound 113C 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
C18 / 32.93 / H42 / 2.65
C19 / 46.67 / H43 / 4.12
C21 / 46.36 / H44 / 5.72
C22 / 153.59
/
Fig.S12. Structure and atom numeration of compound 1
Table S4.Compound 213C 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
C19 / 46.67 / H43 / 4.12
C21 / 46.36 / H44 / 5.72
C22 / 153.59
/
Fig.S13. Structure and atom numeration of compound 2
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
C21 / 45.67 / H45 / 4.05
C22 / 154.91 / H46 / 3.84
C24 / 63.81 / H47 / 3.93
C25 / 13.29 / H48 / 1.21
H49 / 1.54
H50 / 1.58
/
Fig.S14. Structure and atom numeration of compound 3
Table S6. Compound 413C 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
C19 / 46.65 / H42 / 4.30
C21 / 40.86 / H43 / 8.01
C22 / 161.43
/
Fig.S15. Structure and atom numeration of compound 4
Table S7. Compound 513C 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
C17 / 33.82 / H38 / 2.88
C18 / 35.90 / H39 / 1.20
C19 / 48.51 / H40 / 2.90
C21 / 49.93 / H41 / 2.50
/
Fig.S16. Structure and atom numeration of compound 5
Table S9. Compound 613C 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
C22 / 154.72 / H47 / 3.98
C24 / 63.76 / H48 / 1.28
C25 / 13.32 / H49 / 1.50
H50 / 1.53
H51 / 5.09
/
Fig.S17. Structure and atom numeration of compound 6
Table S10. Compound 713C 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
C16 / 146.86 / H36 / 2.57
C17 / 34.32 / H37 / 2.51
C18 / 35.53 / H38 / 2.97
C19 / 48.90 / H39 / 1.18
C21 / 49.86 / H40 / 2.98
H41 / 2.63
/
Fig.S18. Structure and atom numeration of compound 7
References
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4. Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, Cheng D, Jewell K, Arndt D, Sawhney S (2007) HMDB: the Human Metabolome Database. Nucleic Acids Research 35:D521-D526
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