Quantum Computational Investigation of (E)-1-(4-methoxyphenyl)-5-methyl-N′-(3-phenoxybenzylidene)-1H-1,2,3-triazole-4-carbohydrazide
Abstract
:1. Introduction
2. Results and Discussion
2.1. Crystal Structure
2.2. Surface Studies
2.2.1. MEP Surface
2.2.2. Hirshfeld Surface
2.3. Vibrational Analysis
2.3.1. Aromatic C–H, Aliphatic (CH3) and Aromatic C–C Vibrations
2.3.2. Carbohydrazide (N–H, N–N, C=N, C=O) and Other C–O Group Vibrations
2.3.3. 1H-1,2,3-Triazole Ring Vibrations
2.4. NMR Chemical Shift Analyses
2.5. UV–Visible Spectrum and Frontier Orbital Analysis
2.6. Nonlinear Optical (NLO) Properties
2.7. Drug-Likeness and ADME Studies
2.8. Molecular Docking Study
3. Materials and Methods
3.1. Instrumentation
3.2. Synthesis of 2
3.3. Theoretical Details
3.4. Crystal Structure Determination
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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D–H···A | D–H | H···A | D···A | D–H···A |
---|---|---|---|---|
N2–H2A···N3 | 0.86 | 2.39 | 2.763 (5) | 107 |
N7–H7···N8 | 0.86 | 2.38 | 2.752 (5) | 107 |
C17–H17B···O2 | 0.96 | 2.55 | 3.105 (7) | 117 |
C41–H41B···O5 | 0.96 | 2.59 | 3.133 (7) | 116 |
C13–H13···O2 i | 0.93 | 2.45 | 3.316 (5) | 155 |
C41–H41C···N8i | 0.96 | 2.62 | 3.444 (6) | 144 |
C37–H37···O5 ii | 0.93 | 2.45 | 3.334 (5) | 158 |
C17–H17C···N3 ii | 0.96 | 2.65 | 3.486 (6) | 147 |
Structural Parameters | X-ray Diffraction | DFT/B3LYP/6-31++G(d,p) |
---|---|---|
Bond Distances (Å) | ||
C1–O1 | 1.392 (6) | 1.38203 |
C7–O1 | 1.388 (6) | 1.38124 |
C9–C13 | 1.441 (6) | 1.46417 |
C13–N1 | 1.287 (5) | 1.28080 |
N1–N2 | 1.369 (5) | 1.35305 |
N2–C14 | 1.363 (5) | 1.38069 |
C14–O2 | 1.215 (5) | 1.21697 |
C14–C15 | 1.463 (6) | 1.48180 |
C15–N3 | 1.363 (5) | 1.36541 |
N3–N4 | 1.303 (5) | 1.29101 |
N4–N5 | 1.372 (5) | 1.36720 |
N5–C18 | 1.427 (6) | 1.42794 |
C21–O3 | 1.343 (6) | 1.35941 |
O3–C24 | 1.425 (8) | 1.42349 |
Bond angles (°) | ||
C1–O1–C7 | 117.3 (4) | 120.61383 |
C9–C13–N1 | 120.9 (4) | 121.94730 |
C13–N1–N2 | 115.0 (4) | 117.12147 |
N1–N2–C14 | 120.8 (4) | 121.49785 |
N2–C14–O2 | 124.0 (4) | 124.86186 |
N2–C14–C15 | 113.4 (4) | 112.05835 |
C14–C15–C16 | 127.9 (4) | 128.42862 |
C16–N5–C18 | 130.5 (4) | 129.54940 |
N4–N5–C18 | 118.6 (4) | 119.44218 |
C21–O3–C24 | 117.2 (5) | 118.83652 |
Torsion angles (°) | ||
C1–O1–C7–C12 | 35.0 (8) | 41.52414 |
O2–C14–C15–C16 | 14.0 (8) | 2.42954 |
C16–N5–C18–C19 | 137.2 (5) | 128.19985 |
O3–C21–C22–C23 | 177.2 (5) | 179.59354 |
O2–C14–N2–N1 | 1.6 (8) | 1.64013 |
Atom | δexp. | δcalc. | Atom | δexp. | δcalc. |
---|---|---|---|---|---|
C1 | 156.76 | 168.30 | H3 | 7.18 | 7.45 |
C2 | 119.47 | 127.10 | H5 | 7.44 | 7.49 |
C4 | 130.71 | 137.00 | H7 | 7.21 | 7.31 |
C6 | 124.32 | 130.10 | H9 | 7.44 | 7.51 |
C8 | 130.71 | 136.70 | H11 | 7.18 | 7.11 |
C10 | 119.47 | 124.50 | H14 | 7.57 | 8.32 |
C12 | 157.77 | 167.30 | H17 | 7.50 | 7.38 |
C13 | 115.98 | 122.10 | H19 | 7.33 | 7.51 |
C15 | 137.44 | 144.80 | H21 | 7.15 | 7.02 |
C16 | 123.23 | 133.10 | H23 | 8.58 | 8.21 |
C18 | 128.46 | 137.50 | H28 | 2.11 | 2.00 |
C20 | 120.75 | 126.30 | H29 | 2.11 | 3.27 |
C22 | 147.68 | 152.40 | H30 | 2.11 | 2.37 |
C24 | 157.78 | 164.00 | H33 | 7.60 | 7.53 |
C25 | 136.92 | 145.10 | H35 | 7.10 | 7.28 |
C26 | 138.53 | 149.20 | H38 | 7.10 | 7.07 |
C27 | 9.89 | 12.40 | H40 | 7.60 | 7.40 |
C31 | 131.10 | 136.20 | H42 | 3.86 | 3.82 |
C32 | 127.42 | 135.40 | H43 | 3.86 | 4.16 |
C34 | 115.22 | 125.30 | H44 | 3.86 | 3.84 |
C36 | 160.68 | 170.00 | H47 | 12.18 | 10.29 |
C37 | 115.22 | 115.20 | |||
C39 | 127.42 | 134.80 | |||
C41 | 55.85 | 58.60 |
Solvent | λexp. (nm) | Transitions | λcalc. (nm) | f | ΔE (eV) | Computed Major Transitions |
---|---|---|---|---|---|---|
CHCl3 | 293 and 301 | π→π* | 327.30 | 0.6290 | 3.7881 | H→L (93%) |
π→π* | 308.20 | 0.7463 | 4.0228 | H-1→L (90%) | ||
π→π* | 287.25 | 0.0088 | 4.3163 | H-2→L (94%) | ||
π→π* | 271.87 | 0.0001 | 4.5604 | H-6→L (44%), H-7→L (35%) | ||
π→π* | 271.00 | 0.0078 | 4.5750 | H-3→L (72%) | ||
π→π* | 263.06 | 0.0236 | 4.7132 | H→L + 1 (83%), H-1→L + 1 (12%) | ||
MeOH | 293 and 299 | π→π* | 327.61 | 0.5721 | 3.7845 | H→L (92%) |
π→π* | 308.08 | 0.7446 | 4.0244 | H-1→L (69%), H-2→L (24%) | ||
π→π* | 293.23 | 0.0560 | 4.2283 | H-2→L (71%), H-1→L (27%) | ||
π→π* | 271.83 | 0.0079 | 4.5612 | H-3→L (71%), H-4→L (11%) | ||
π→π* | 269.00 | 0.0003 | 4.6091 | H-7→L (73%), H-6→L (13%) | ||
π→π* | 259.93 | 0.0572 | 4.7699 | H→L + 1 (68%), H-1→L + 1 (22%) | ||
MeCN | 292 and 298 | π→π* | 327.75 | 0.5797 | 3.7829 | H→L (93%) |
π→π* | 308.21 | 0.7388 | 4.0227 | H-1→L (68%), H-2→L (25%) | ||
π→π* | 293.35 | 0.0552 | 4.2264 | H-2→L (71%), H-1→L (28%) | ||
π→π* | 271.85 | 0.0080 | 4.5607 | H-3→L (71%), H-4→L (11%) | ||
π→π* | 268.96 | 0.0003 | 4.6098 | H-7→L (73%), H-6→L (13%) | ||
π→π* | 259.91 | 0.0594 | 4.7703 | H→L + 1 (67%), H-1→L + 1 (23%) | ||
DMF | 299 | π→π* | 328.38 | 0.6195 | 3.7757 | H→L (94%) |
π→π* | 308.81 | 0.7133 | 4.0149 | H-1→L (67%), H-2→L (27%) | ||
π→π* | 293.55 | 0.0459 | 4.2236 | H-2→L (69%), H-1→L (29%) | ||
π→π* | 271.90 | 0.0083 | 4.5599 | H-3→L (71%), H-4→L (11%) | ||
π→π* | 268.95 | 0.0003 | 4.6099 | H-7→L (73%), H-6→L (13%) | ||
π→π* | 259.98 | 0.0656 | 4.7690 | H→L + 1 (66%), H-1→L + 1 (24%) |
Parameters | CHCl3 (ε = 4.7113) | MeOH (ε = 32.613) | MeCN (ε = 35.688) | DMF (ε = 37.219) |
---|---|---|---|---|
ELUMO (eV) | −2.0169 | −2.1089 | −2.1105 | −2.1111 |
EHOMO (eV) | −6.2902 | −6.3705 | −6.3718 | −6.3724 |
Energy bandgap |EHOMO−ELUMO| (eV) | 4.2733 | 4.2616 | 4.2613 | 4.2613 |
Ionization potential (I = −EHOMO) (eV) | 6.2902 | 6.3705 | 6.3718 | 6.3724 |
Electron affinity (A = −ELUMO) (eV) | 2.0169 | 2.1089 | 2.1105 | 2.1111 |
Chemical hardness (η = (I − A)/2) (eV) | 2.1366 | 2.1308 | 2.1307 | 2.1307 |
Chemical softness (ζ = 1/2η) (eV−1) | 0.2340 | 0.2347 | 0.2347 | 0.2347 |
Electronegativity (χ = (I + A)/2) (eV) | 4.1535 | 4.2397 | 4.2412 | 4.2417 |
Chemical potential (μ = −(I + A)/2) (eV) | −4.1535 | −4.2397 | −4.2412 | −4.2417 |
Electrophilicity index (w = μ2/2η) (eV) | 4.0372 | 4.2179 | 4.2211 | 4.2222 |
Maximum charge transfer index (ΔNmax. = −μ/η) | 1.9440 | 1.9897 | 1.9905 | 1.9908 |
MeCN | CHCl3 | ||||||
---|---|---|---|---|---|---|---|
P | Value (esu) | P | Value (esu) | P | Value (esu) | P | Value (esu) |
αxx | 1.06054264 × 10−22 | βxxx | 2.7232392281 × 10−29 | αxx | 1.02029387 × 10−22 | βxxx | 2.3952996201 × 10−29 |
αxy | 3.34406970 × 10−24 | βxyy | −6.7163351322 × 10−30 | αxy | 2.71384369 × 10−24 | βxyy | −5.3041591257 × 10−30 |
αxz | −1.96406718 × 10−25 | βxzz | 3.9775500915 × 10−31 | αxz | −1.74450518 × 10−26 | βxzz | 3.4264850753 × 10−31 |
αyy | 6.14781650 × 10−23 | βyyy | 2.5742850132 × 10−30 | αyy | 5.53813340 × 10−23 | βyyy | 1.9066353494 × 10−30 |
αyz | 5.61089698 × 10−24 | βyxx | −4.2660804480 × 10−30 | αyz | 4.95659385 × 10−24 | βyxx | −3.8201464576 × 10−30 |
αzz | 4.89191925 × 10−23 | βyzz | 4.1525419899 × 10−31 | αzz | 4.34111794 × 10−23 | βyzz | 2.7472139962 × 10−31 |
αtotal | 72.1505403 × 10−24 | βzzz | −7.2495596707 × 10−31 | αtotal | 66.9406335 × 10−24 | βzzz | −4.4045838309 × 10−31 |
Δα | 53.2230869 × 10−24 | βzxx | −6.2103327791 × 10−31 | Δα | 54.5298916 × 10−23 | βzxx | −4.5456621571 × 10−31 |
μx | −1.9477408 | βzyy | 4.0011609701 × 10−31 | μx | −1.9675829 | βzyy | 2.6810099604 × 10−31 |
μy | 0.2212355 | β0 | 209.74073818 × 10−31 | μy | 0.2212355 | β0 | 190.72367172 × 10−31 |
μz | 0.079071 | μz | 0.0277634 | ||||
μtotal | 1.9618592 | μtotal | 1.9801764 | ||||
MeOH | DMF | ||||||
P | Value (esu) | P | Value (esu) | P | Value (esu) | P | Value (esu) |
αxx | 1.05991420 × 10−22 | βxxx | 2.7186313156 × 10−29 | αxx | 1.06081731 × 10−22 | βxxx | 2.7252481965 × 10−29 |
αxy | 3.33205805 × 10−24 | βxyy | −6.6900564567 × 10−30 | αxy | 3.34934748 × 10−24 | βxyy | −6.7278538996 × 10−30 |
αxz | −1.93663892 × 10−25 | βxzz | 3.9658089890 × 10−31 | αxz | −1.97595431 × 10−25 | βxzz | 3.9828977750 × 10−31 |
αyy | 6.13687028 × 10−23 | βyyy | 2.5625263928 × 10−30 | αyy | 6.15261523 × 10−23 | βyyy | 2.5794420947 × 10−30 |
αyz | 5.60026327 × 10−24 | βyxx | −4.2586482569 × 10−30 | αyz | 5.61554695 × 10−24 | βyxx | −4.2692974780 × 10−30 |
αzz | 4.88130109 × 10−23 | βyzz | 4.1222501073 × 10−31 | αzz | 4.89658696 × 10−23 | βyzz | 4.1658927840 × 10−31 |
αtotal | 72.0577113 × 10−24 | βzzz | −7.1870785944 × 10−31 | αtotal | 72.1912509 × 10−24 | βzzz | −7.2771077289 × 10−31 |
Δα | 53.2598403 × 10−24 | βzxx | −6.1728143986 × 10−31 | Δα | 53.2068187 × 10−24 | βzxx | −6.2270660838 × 10−31 |
μx | −1.9482024 | βzyy | 3.9736307175 × 10−31 | μx | −1.9475465 | βzyy | 4.0132371478 × 10−31 |
μy | 0.2190976 | β0 | 209.53283113 × 10−31 | μy | 0.2221764 | β0 | 209.83099781 × 10−31 |
μz | 0.0777472 | μz | 0.0796567 | ||||
μtotal | 1.9620247 | μtotal | 1.9617963 |
Value | MeCN | CHCl3 | MeOH | DMF |
---|---|---|---|---|
αtotal | 14.21 | 13.19 | 14.19 | 14.22 |
∆α | 24.92 | 25.53 | 24.94 | 24.91 |
β0 | 29.04 | 26.41 | 29.01 | 29.05 |
SMILES | COc1ccc(cc1)n1nnc(c1C)C(=O)N/N=C/c1cccc(c1)Oc1ccccc1 |
---|---|
Physicochemical Properties | Values |
Molecular weight (MW) | 427.16 g/mol |
Number of heavy atoms | 32 |
Number of aromatic heavy atoms | 23 |
Fraction Csp3 | 0.08 |
Number of rotatable bonds | 8 |
Number of H-bond acceptors (HBA) | 6 |
Number of H-bond donors (HBD) | 1 |
Molar refractivity (MR) | 120.50 |
Topological polar surface area (TPSA) | 90.63 Å2 |
Lipophilicity | Values |
LogPo/w (iLOGP) | 3.82 |
LogPo/w (XLOGP3) | 4.49 |
LogPo/w (WLOGP) | 4.14 |
LogPo/w (MLOGP) | 3.00 |
LogPo/w (SILICOS-IT) | 3.59 |
Consensus LogPo/w | 3.81 |
Water solubility | Values |
Log S (ESOL) | −5.32 |
Solubility | 2.03 × 10−3 mg/mL; 4.76 × 10−6 mol/L |
Class | Moderately soluble |
LogS (Ali) | −6.11 |
Solubility | 3.29 × 10−4 mg/mL; 7.70 × 10−7 mol/L |
Class | Poorly soluble |
LogS (SILICOS-IT) | −7.83 |
Solubility | 6.25 × 10−6 mg/mL; 1.46 × 10−8 mol/L |
Class | Poorly soluble |
Pharmacokinetics | Values |
Gastrointestinal (GI) absorption | High |
Blood–brain barrier (BBB) permeant | No |
P-glycoprotein (P-gp) substrate | No |
CYP1A2 inhibitor | No |
CYP2C19 inhibitor | Yes |
CYP2C9 inhibitor | Yes |
CYP2D6 inhibitor | No |
CYP3A4 inhibitor | Yes |
LogKp (skin permeation) | −5.72 cm/s |
Drug-likeness | Values |
Lipinski | Yes; zero violation |
Ghose | Yes |
Veber | Yes |
Egan | Yes |
Muegge | Yes |
Bioavailability score | 0.55 |
Medical chemistry | Values |
PAINS | 0 alert |
Brenk | 1 alert: imine_1 |
Lead-likeness | No; three violations: MW > 350, rotors > 7; XLOGP3 > 3.5 |
Synthetic accessibility | 3.52 |
Mode | Binding Affinity (kcal/mol) | Distance from the Best Mode (Å) | |
---|---|---|---|
RMSD/lb | RMSD/ub | ||
1 | −10.10 | 0.000 | 0.000 |
2 | −9.90 | 2.271 | 9.987 |
3 | −9.80 | 1.851 | 10.125 |
4 | −9.60 | 2.361 | 10.036 |
5 | −9.50 | 3.371 | 9.958 |
6 | −9.10 | 1.826 | 10.625 |
7 | −9.00 | 14.962 | 17.748 |
8 | −8.80 | 2.062 | 2.664 |
9 | −8.70 | 2.603 | 4.106 |
10 | −8.60 | 15.096 | 18.245 |
Chemical Formula | C24H21N5O3 |
---|---|
Formula weight | 426.46 |
F(000) | 896 |
Radiation | CuKα (λ = 1.54184 Å) |
Crystal system | Triclinic |
Space group | P |
a, b, c (Å) | 6.6452 (5), 7.4466 (5), 43.403 (2) |
α, β, γ (°) | 86.250 (4), 89.193 (5), 80.484 (6) |
Volume (Å3) | 2113.7 (2) |
Z | 4 |
Crystal dimension (mm) | 0.30 × 0.18 × 0.03 |
Temperature (K) | 293 |
Dcalc (mg m−3) | 1.343 |
Measured reflections | 9077 |
Independent reflections | 9077 |
Number of reflections with I > 2 σ(I) | 6949 |
θ range (°) | 6.0–77.1 |
Range of h, k, l | −8 < h < 8, −9 < k < 9, −54 < l < 52 |
Refinement on | F2 |
Calculated weights | W = 1/(σ2(Fo2) + (0.1235P)2 + 1.0892P), where P = (Fo2 + 2Fc2/3) |
Number of refinement parameters | 582 |
S | 1.08 |
R (F2 > 2σ(F2)) | 0.075 |
wR (F2) | 0.241 |
(Δρ)max (e Å−3) | 0.30 |
(Δρ)min (e Å−3) | −0.23 |
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Gökce, H.; Şen, F.; Sert, Y.; Abdel-Wahab, B.F.; Kariuki, B.M.; El-Hiti, G.A. Quantum Computational Investigation of (E)-1-(4-methoxyphenyl)-5-methyl-N′-(3-phenoxybenzylidene)-1H-1,2,3-triazole-4-carbohydrazide. Molecules 2022, 27, 2193. https://doi.org/10.3390/molecules27072193
Gökce H, Şen F, Sert Y, Abdel-Wahab BF, Kariuki BM, El-Hiti GA. Quantum Computational Investigation of (E)-1-(4-methoxyphenyl)-5-methyl-N′-(3-phenoxybenzylidene)-1H-1,2,3-triazole-4-carbohydrazide. Molecules. 2022; 27(7):2193. https://doi.org/10.3390/molecules27072193
Chicago/Turabian StyleGökce, Halil, Fatih Şen, Yusuf Sert, Bakr F. Abdel-Wahab, Benson M. Kariuki, and Gamal A. El-Hiti. 2022. "Quantum Computational Investigation of (E)-1-(4-methoxyphenyl)-5-methyl-N′-(3-phenoxybenzylidene)-1H-1,2,3-triazole-4-carbohydrazide" Molecules 27, no. 7: 2193. https://doi.org/10.3390/molecules27072193