New palladium (II) and silver (I) Schiff base complexes Promising - - PowerPoint PPT Presentation

7thInternational Chemistry Conference 12th - 14th November 2018 Riyadh, Saudi Arabia

New palladium (II) and silver (I) Schiff base complexes Promising antibiotic and anticancer agents

Laila H Abdel-Rahman, Ahmed M Abu-Dief, Azza A Hassan Abdel-Mawgoud

Reflux for 1-3 h at 80 C

HN HNA Reflux 4-6h metal salt HNAPd HNAAg HNAV Stirring A

OH CHO

H2N HO O O V N O O O

H2O

O Pd N O O H2O HO Ag N O O H2O

.2H2O

Characterization of the prepared imine ligand and their complexes

Characterization of the investigated ligands and their complexes

• Fig. 1: 1H NMR spectrum of HNA imine ligand
• Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha and Azza A.

Hassan Abdel-Mawgoud, accepted manuscript, Applied organometallic Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

• Fig. 2: 13C NMR spectrum of HNA imine ligand.
• Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha

and Azza A. Hassan Abdel-Mawgoud, accepted manuscript, Applied organometallic Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

Compounds (Molecular formula)

• M. wt

Color Yield (%)

• M. p and
• Dec. temp

(o C) Analysis (%) Found (Calcd.) C H N HNA C18H13NO3 291.32 Yellow (93) 280 74.07 (74.15) 4.40 (4.46) 4.77 (4.81) HNAPd C18H13NO4Pd 413.40 Dark orange (90) ( >300) 51.34 )52.25) 3.05 )3.14) 3.33 )3.39) HNAV C18H13NO5V 373.94 Black (86) (>300) 47.99 )47.79) 3.92 )3.98) 3.01 )3.09) HNAAg C18H18NO6Ag 451.90 Light brown (91) (>300) 52.03 )51.94) 3.19 )3.37) 3.38 )3.37)

Analytical and physical data of the prepared imine ligands and their complexes

• Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha and Azza A.

Hassan Abdel-Mawgoud, accepted manuscript, Applied organometallic Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

• Laila H. Abdel-Rahmana, Ahmed M. Abu-Diefa, Moustafa O. Aboelez, Azza A. Hassan

Abdel-MawgoudaJournal of Photochemistry & Photobiology, B: Biology 170 (2017) 271–285

FT-IR spectrum of HNA imine ligand. FT-IR spectrum of HNAAg complex. Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha and Azza A. Hassan Abdel-Mawgoud, accepted manuscript, Applied organometallic Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

4000 3500 3000 2500 2000 1500 1000 500 0.4 0.5 0.6 0.7 0.8 0.9 1.0

Transmission (%) Wave number (cm

• 1)

4000 4000 3500 3500 3000 3000 2500 2500 2000 2000 1500 1500 1000 1000 500 500 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

Transmission (%) Wave number (cm

• 1)

The infrared absorption frequencies (cm-1)a of the investigated imine ligands and their complexes

Comp. υ)OH)/H2 O υSt (-C=N)

ʋ(CH)ar

υph(C-O) υph(V=O) υ )M-O) υ )M-N) HNA 3425 (m) 1613 (s) 3097 1279 (m)

• HNAPd

3423 (s)

1587 (s)

3053 (w) 1269 (s)

• 583 (s)

469 (w) HNAAg 3422 (s) 1589 (s) 3025 (w) 1276 (m)

• 568 (w)

497 (w) HNAV 3443 (s) 1593 (s) 3063 (m) 1247 (s) 968 573 (s) 421( m)

S = strong, m = medium, w = weak, Ar = aromatic, A = aliphatic, ph = phenolic, As = Asymmetric, S = Symmetric, St = Stretching

• Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha and Azza A.

Hassan Abdel-Mawgoud, accepted manuscript, Applied organometallic Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

• Laila H. Abdel-Rahmana, Ahmed M. Abu-Diefa, Moustafa O. Aboelez, Azza A. Hassan Abdel-

MawgoudaJournal of Photochemistry & Photobiology, B: Biology 170 (2017) 271–285

• Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha and Azza A.

Hassan Abdel-Mawgoud, accepted manuscript, Applied organometallic Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

• Laila H. Abdel-Rahmana, Ahmed M. Abu-Diefa, Moustafa O. Aboelez, Azza A. Hassan

Abdel-MawgoudaJournal of Photochemistry & Photobiology, B: Biology 170 (2017) 271– 285

200 300 400 500 600 0.0 0.5 1.0 1.5 2.0

Abs

,(nm)

HNA(II) HNAPd HNAVO HNAAg

C A A A A K

m m f 2

1        

Xligand = 0.56

Continuous variation plots for the prepared complexes in aqueous-alcoholic mixture at 298 K. The stoichiometry and the stability constants of the prepared complexes have been determined spectrophotometrically

Abdel-Rahman, L. H. , Abu-Dief, A. M. , Hamdan, S. K., Seleem, A. A., Int. J. Nano.

• Chem. 1, No. 2, (2015) 65 - 77.
• Laila H. Abdel-Rahmana, Ahmed M. Abu-Diefa, Moustafa O. Aboelez, Azza A. Hassan Abdel-

MawgoudaJournal of Photochemistry & Photobiology, B: Biology 170 (2017) 271–285

Abdel-Rahman, L.H., El-Khatib, R.M., Abu-Dief, A.M., Abdel-Fatah, S.M., ., J.

• Photochem. Photobio B. 162, 298–308 [2016 ].

0.0 0.2 0.4 0.6 0.8 1.0 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8

HNAPd HNAV HNAAg-0.1

[L]/ [L]+[M] Abs

Molar ratio plots for the prepared complexes in aqueous-alcoholic mixture 298 K.

Molar ratio method

• Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha and

Azza A. Hassan Abdel-Mawgoud, accepted manuscript, Applied

• rganometallic

Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

• Laila H. Abdel-Rahmana, Ahmed M. Abu-Diefa, Moustafa O. Aboelez, Azza A.

Hassan Abdel-MawgoudaJournal of Photochemistry & Photobiology, B: Biology

170 (2017) 271–285

0.0 0.5 1.0 1.5 2.0 2.5 3.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6

Abs

[L]/ [M]

HNAAg HNAPd HNAV

Thermal analysis of the prepared HNA imine complexes

Complexes Temperature

• C

Fragment loss % Weight loss % Molecular formula

• M. Wt. Found

Calc. HNAPd 33- 171 oC H2O 18 4.33 (4.35) 173-380 oC C7H4O2 120 29.07 (29.03) 382- 563 oC C11H7N 153 36.99 (37.01) Residue > 563 oC PdO 122.40 29.58 (29.61) HNAV 35-187 oC H2O 18 4.80 (4.81) 189-373 oC C7H4O2 120 32.11 32.09 375-586 oC C11H7NO 169 45.16 45.19 Residue >586 oC VO 66.94 17.88 17.90 HNAAg 35- 110 oC 2 H2O 36 7.99 (7.97) 112- 191 oC H2O 18 3.99 (3.98) 193- 377 oC C7H4O 104 23.07 (23.01) 379- 642 oC C11H8 139 30.77 (30.76) Residue > 642 oC 0.5Ag2O+0.5N2O3 153.90 34.05 (34.06)

Kinetic and thermodynamic parameters studies of the prepared metal complexes

RT E E RT E AR W W W

T

303 . 2 2 1 log )) /( log( log

* * *

2

                     

 



ΔH* = E* - RT

ΔG* = ΔH* - TΔS

Complex Decomp. Temp. ( oC) E* (KJmol-1) A (S-1) ∆H* (KJmol-1) ∆G* (KJmol-1) ∆S* (Jmol-1K-1)

HNAPd

102 15.90 0.031 15.10 42.10

• 264.92

276 13.60 89.00

• 273.19

473 11.97 143.30

• 277.68

HNAV

111 51.70 0.10 50.80 79.20

• 255.88

281 49.40 123.50

• 263.61

480 48.00 176.70

• 268.06

HNAAg

72 15.60 0.027 15.19 31.10

• 259.17

113 14.70 44.90

• 266.92

285 13.20 91.50

• 274.61

510 11.40 153.90

• 279.45
• Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha and Azza

A. Hassan Abdel-Mawgoud, accepted manuscript, Applied

• rganometallic

Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

Molar conductivity of the prepared complexes at 298 K

Complex es Conc. Mol dm-3 Molar conductance ᴧm, Ohm-1 cm2 mol-1 μeff (B. M.) Geometry HNAPd 1 × 10-3 24.00 Diamagnetic Square planer HNAV 2 × 10-3 15.00 1.76 Distorted Square Pyramidal HNAAg 1 × 10-3 5.68 Diamagnetic Tetrahedral

Molar conductivity and Magnetic moment measurements

pH stability

• A. Roth, E.T. Spielberg, W. Plass, Inorg. Chem. 46 , 2007, 4362–4364.
• L. H. Abdel-Rahman, R. M. El-Khatib, L. A. E. Nassr, A.M. Abu-Dief, J. Mol. Struct. 2013, 1040, 9.
• L. H. Abdel-Rahman, R. M. El-Khatib, L.A.E. Nassr, A. M. Abu-Dief, F.E. Lashin, Spectrochim. Acta A 2013, 111, 266-276.
• L. H. Abdel-Rahman, R. M. El-Khatib, L. A. E. Nassr, A. M. Abu-Dief, A. A. Seleem, Spectrochim. Acta A 2014, 117, 366.
• A. M. Abu-Dief and L. A. E. Nassr, J. Iran. Chem. Soc. 2015, 12 943-955.
• L. H. Abdel-Rahman, A. M. Abu-Dief, S. K. Hamdan, A. A. Seleem, Int. J. Nano. Chim. 2015, 1 (2) 65 – 77
• L. H. Abdel-Rahman, A. M. Abu-Dief, M., Ismael, M. A. A., Mohamed, N. A. Hashem, J. Mol. Struct. 2016, 1103, 232– 244

2 4 6 8 10 12 14

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6

pH

Abs

HNAAg+0.05 HNAPd HNAV

The suggested structure for the prepared complexes

O Pd N O O H2O

O V N O O O

H2O

HO Ag N O O H2O

.2H2O

Theoretical modeling calculations of HNA imine ligand and its complexes

Optimized bond lengths, bond angles and dihedral angles of thestudied complexes using B3LYP/LANL2DZ

Type of bond Bond length )Å) Type of Angle Angle () Type of Angle Angle () Pd-N1 1.981 N1-Pd-O1 93.20 N1-Pd-O4 173.1 Pd-O1 2.005 N1-Pd-O2 95.40 O1-Pd-O2 170.1 Pd-O2 1.994 O1-Pd-O4 93.63 O2-N1-O1- O4 2.831 Pd-O4 2.120 O2-Pd-O4 77.74 V-N1 2.044 N1-V-O1 87.72 O5-V-N1 101.9 V-O1 1.910 N1-V-O2 86.91 O5-V-O1 114.1 V-O2 1.909 O1-V-O4 83.90 O5-V-O2 115.6 V-O4 2.061 O2-V-O4 77.52 O5-V-O4 107.0 V-O5 1.598 O2-N1-O1- O4 11.74*

Calculated lowest total energy (E), highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), energy gap )∆E) and dipole moment )Debye) of imines and their complexes at B3LYP/LANL2DZ. Parameter HNA HNAPd HNAVO Total E (au)

• 974.230
• 1176.07
• 1196.04

HOMO (au)

• 0.2275
• 0.2159
• 0.2284

LUMO (au)

• 0.0919
• 0.0952
• 0.1015

∆E )eV) 3.6897 3.2842 3.4529 dipole moment (Debye) 7.900 6.094 6.705

Theoretical modeling calculations of HNA imine complexes

Molecular electrostatic potential surface of compounds of ligand (HNA) and complexes (HNAPd and HNAVO) using B3LYP/LANL2DZ.

 HOMO and LUMO charge density maps of ligand

(HNA) and complexes (HNAPd and HNAVO) using B3LYP/LANL2DZ.

• Tri- imine ligand based on 2-hydroxynapthaldehyde (HN) with

Anthrinilic acid (A) has been prepared.

• The prepared imine ligand was analyzed by their melting points, 1H

NMR, 13C NMR spectra, elemental analysis, UV-Vis and IR spectra.

• Molecular structures of the prepared imine complexes were

identified via their decomposition temperatures, elemental analyses, IR, UV/ Vis, TGA, conductivity and magnetic susceptibility measurements.

• Moreover, the stoichiometry and the stability constants of the

prepared complexes have been determined spectrophotometrically .

• Spectral scans in different pH values revealed that is a wide range of

pH stability of the investigated complexes ) ̴ 4 -11 ).

Pharmaceutical applications

Anticancer activity

Antimicrobial activity

Docking Studies DNA interaction

Microccus luteus

Getrichm Candidum

Antimicrobial activity

• Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha and Azza A. Hassan Abdel-

Mawgoud, accepted manuscript, Applied organometallic Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

• Laila H. Abdel-Rahmana, Ahmed M. Abu-Diefa, Moustafa O. Aboelez, Azza A. Hassan

Abdel-MawgoudaJournal of Photochemistry & Photobiology, B: Biology 170 (2017) 271– 285

10 15 20 25

4 8 12 16 20 24 28 32 36 40

HNAAg HNAVO HNAPd HNA Inhibition zone (cm)

mg/ml 10 15 20

3 6 9 12 15 18 21 24 27 30 33 36

HNAAg HNAVO HNAPd HNA Inhibition zone (cm)

mg/ml

Determination of the activity index (A) for the prepared compounds

Inhibition Zone of compound (mm) Inhibition Zone of standard drug (mm) Activity index (A) = x 100

Activity index (%) Comp. Fungi Bacteria Aspergillus flavus Getrichm candidum Fusarium

• xysporum

Microccus Luteus (+ve) Serratia Marcescence (-ve)

• E. coli

29.17 25.64 30.00 29.27 34.48 20.83 HNA 91.67 89.74 86.67 87.80 86.21 83.33 HNAPd 87.50 87.18 83.33 85.37 82.76 70.83 HNAAg 79.17 84.62 80.00 80.49 75.86 66.67 HNAVO

Gel Electrophoreses Spectrophotometric Study

Hydrodynamic method

DNA –binding studies

Plot of [DNA] / (εa - εf) versus [DNA] for the titration of DNA with HNAPd complex Spectral scans of the interaction of HNAPd complex ( 10-3 mol dm-3) in 0.01 mol dm-3 Tris buffer (pH 7.2, 298 K) with CT- DNA (0 - 30) µM DNA, from top to bottom

DNA interaction using electronic spectra

200 250 300 350 400 450 500 550 0.0 0.5 1.0 1.5 2.0 2.5 HNAPd HNAPd+ DNA

Abs

,(nm)

20 40 60 80 100 120 100 200 300 400

10

6[DNA]

10

9[DNA]/(a-f)

Spectral parameters for DNA interaction with the prepared imine complexes

• Laila H. Abdel-Rahman, Nabawia M. Ismail, Mohamed Ismael, Ahmed M.

Abu-Dief and Ebtehal Abdel-Hameed Ahmed, Journal of Molecular Structure 1134 (2017) 851-862.

• Laila H. Abdel-Rahman, Ahmed M. Abu-Dief, Maram Basha and Azza A.

Hassan Abdel-Mawgoud, accepted manuscript, Applied organometallic Chemistry ,2017, e3750. https:// doi.org/10.1002/aoc.3750

• Laila H. Abdel-Rahmana, Ahmed M. Abu-Diefa, Moustafa O. Aboelez, Azza A. Hassan

Abdel-MawgoudaJournal of Photochemistry & Photobiology, B: Biology 170 (2017) 271–285

Com plex λmax free (nm) λmax bound (nm) ∆n Chromism (%)a Type of Chromis m Binding Constant 104 (Kb)b ∆G* (KJmol-

1)

HNA Pd 481 356 289 250 239 463 354 270 251 238 18 2 19 1 1 8.85 7.51 5.08 9.95 9.63 Hypo Hyper Hypo Hyper Hyper 7.41

• 27.78

HNA VO 431 353 252 239 430 349 250 238 1 4 2 1 28.25 1.79 12.57 12.90 Hypo Hypo Hyper Hyper 7.11

• 27.68

HNA Ag 451 449 2 17.18 Hypo 9.08

• 28.29

319 316 3 17.02 Hypo 252 239 13 6.06 Hyper

30

η = )t-t°)/ t°

The effect of increasing the amount of the synthesized complexes on the relative viscosities of DNA at [DNA] = 0.5 mM, [complex] = 25 - 250 µM and 298 K.

• L. H.Abdel-Rahman, , Abu-Dief, A. M. , Hamdan, S. K., Seleem, A. A., Int. J. Nano. Chem. 1, No.

2, (2015) 65 - 77. Laila H. Abdel-Rahmana, Ahmed M. Abu-Diefa, Moustafa O. Aboelez, Azza A. Hassan Abdel-MawgoudaJournal of Photochemistry & Photobiology, B: Biology 170 (2017) 271–285

Viscosity measurements

0.0 0.1 0.2 0.3 0.4 0.5 1.05 1.20 1.35 1.50 [Complex]/ [DNA]



1/3

HNAV EB HNAPd HNAAg

DNA binding results of the prepared imine complexes based on gel

• electrophoresis. Lane 1: DNA Ladder, lane 2: HNAPd+ DNA, lane

3: HNAV+ DNA, lane 4: HNAAg+ DNA; lane 5: HNAV+ DNA; lane 6: HNAPd.

Gel electrophoresis

Laila H. Abdel-Rahman, A.M. Abu-Dief, M.O .Aboelez, AAH Abdel- Mawgoud, Journal of Photochemistry and Photobiology B: Biology, Journal of Photochemistry & Photobiology, B: Biology 170 (2017) 271–285

• S. Tabassum, M. Zaki, M. Afzal, F. Arjmand, Dalton Trans. 2013, 42, 10029– 10041.
• L. H. Abdel-Rahman, R. M. El-Khatib, L. A. E. Nassr, A.M. Abu-Dief, J. Mol. Struct. 2013, 1040, 9.
• L. H. Abdel-Rahman, R. M. El-Khatib, L.A.E. Nassr, A. M. Abu-Dief, F.E. Lashin, Spectrochim. Acta A 2013, 111, 266-276.
• L. H. Abdel-Rahman, R. M. El-Khatib, L. A. E. Nassr, A. M. Abu-Dief, A. A. Seleem, Spectrochim. Acta A 2014, 117, 366.

] A. M. Abu-Dief and L. A. E. Nassr, J. Iran. Chem. Soc. 2015, 12 943-955.

• L. H. Abdel-Rahman, A. M. Abu-Dief, S. K. Hamdan, A. A. Seleem, Int. J. Nano. Chim. 2015, 1 (2) 65 – 77
• L. H. Abdel-Rahman, A. M. Abu-Dief, M., Ismael, M. A. A., Mohamed, N. A. Hashem, J. Mol. Struct. 2016, 1103, 232– 244.

Mode of DNA interaction

• The presence of metal binding sites in DNA structure make different type of interactions

possible such as:

• Minor and major groove binding, electrostatic and interclation
• Major groove binding which play an important role in the efforts of the drug targeted to

DNA.

• A large number of transition metal complexes have been used as potential DNA-targeted

antitumor drugs

Suggested mechanism for interaction of HNAPd with DNA via (A) intercalation binding and (B) replacement.

H2O

H2O

A B

O N

O

O

Pd

O N

O

O

Pd Interaction with DNA Interclation Replacement

Anticancer activity evaluation

IC50 values of the HNA ligand and its complexes against human Colon carcinoma cells, (HCT-116 cell line) and colon carcinoma cells, (MCF-7 cell line).

Anticancer activity

Molecular Docking studies

The proposed binding mode of HNA ligand in surface docking

Laila H. Abdel-Rahman, A.M. Abu-Dief, M.O .Aboelez, AAH Abdel- Mawgoud, Journal of Photochemistry and Photobiology B: Biology, Journal

• f Photochemistry & Photobiology, B: Biology 170 (2017) 271–285

Molecular Docking studies

The proposed binding mode of HNAAg complex in solid surface docking.

The proposed binding mode of HNAPd complex in hydrophobic docking.

Laila H. Abdel-Rahman, A.M. Abu-Dief, M.O .Aboelez, AAH Abdel- Mawgoud, Journal of Photochemistry and Photobiology B: Biology, Journal

• f Photochemistry & Photobiology, B: Biology 170 (2017) 271–285

• The in-vitro biological evaluations of the prepared compounds against

various microbial strains showed that the metal complexes exhibit higher antimicrobial activity than free ligands.

• The interaction of these complexes with (CT-DNA) was investigated by using

spectrophotometry, viscosity and agarose gel electrophoresis measurements and the results showed that the prepared complexes bind to the calf thymus (CT- DNA) mainly via intercalative mode.

• The in vitro cytotoxicity (IC50) of the investigated complexes were tested against

colon carcinoma cells, (HCT-116 cell line), Breast carcinoma cells, (MCF-7 cell line) and hepatic cellular carcinoma cells, (HepG-2).

• All the prepared complexes displayed significantly cytotoxic activities (which are

greater than that of ligand) compared to vinblastine standard drug.

• Molecular docking as a powerful approach for structure-based drug

discovery was done for the optimization of the investigated compounds as potential TRK inhibitors

Thank you for attention!