[PPT] - 1 Sohag University PowerPoint Presentation

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Ahmed Mohammed Abu-Dief

Presented By

"Physicochemical and Biological Studies: Embryos Toxicity,

DNA Interaction and In Vitro Antimicrobial activity of Some New Iron(II) Schiff base Amino Acid Complexes."

Sohag University Faculty of Science

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Under Supervision

Prof. Dr.

Laila Hamdan Abd El-Rhman Dr. Rafat M. El- Khatib Lobna A. Ebaid Nassr

Prof. of Inorganic Chemistry,

Faculty of Science, Sohag University

Assistant Prof. of Inorganic Chemistry, Faculty of Science, Sohag University

Dr.

Assistant Prof. of physical chemistry, Faculty of Science, Sohag University

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Introduction.
Highlights of the work.
Over view of results

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Schiff Bases are characterized by the >C=N (imine) group which

imports in elucidating the mechanism of transamination reaction in biological system

Schiff bases derived from primary amines and substituted

benzaldehydes exhibit antibacterial, anticancer, and antitumor

activity. Numerous studies have shown that such an activity of

Schiff bases is caused by the presence of the >C=N[1]

Schiff bases have catalytic activity in hydrogenation of olefins and

complexing ability towards some toxic metals[2]

[1] Sandermann, W., Naturharze Terpentinol-TalloChemie und Technologie, Berlin: Springer, 1960,303-310

[2]Gehad G. MOHAMED, Mohamed M. OMAR, Ahmed M. HINDY, Turk J Chem,30 (2006) , 361

– 38

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The high affinity for the chelation of the Schiff bases towards the

transition metal ions is utilized in preparing their solid complexes

Metal

complexes play an essential role in agriculture, pharmaceutical and industrial chemistry.

Schiff base metal complexes have been widely studied because

they have industrial, antifungal [3], antibacterial [4], anticancer [5] and herbicidal applications[6]

[3]- Daniel, V. P.; Murukan, B.; Kumari, B. S.; Mohanan, K. Spectrochim Acta Part A 2008, 70, 403. [4]-Prashanthi, Y.; Kiranmai, K.; Subhashini, N. J. P.; Shivaraj, S. Spectrochim Acta Part A 2008, 70, 30. [5]- Galal, S. A.; Hegab, K. H.; Kassab, A. S.; Rodriguez, M. L.; Kerwin, S. M.; El-Khamry, A.-M. A.; El Diwani, H. I. Eur J Med Chem 2009, 44(4), 1500. [6]-Cozzi, P.G., Chem. Soc. Rev. 2004, 33, 410-42

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Schiff base complexes have extensive importance as radiotracers in nuclear medicine[7]

Monamine oxidase enzyme B

[7]Du Preez, J. G. H.; Gerber, T. I. A.; Fourie, P. J.; Van Wyk, A. J., J. Coord. Chem., 1984, 13, 173

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Aromatic Schiff bases and their metal complexes are used as catalysts for:

Oxidation[8].
Epoxidation[9].
Polymerization[10].
Decomposition and hydrolysis reactions[11].
Synthetic Iron (II) Schiff base complexes exhibit

catalytic activity to electro-reduction of oxygen[12].

[8]Sheldon, R. A.; Kochi, J. K., Metal Catalyzed Oxidations of Organic Compounds; Academic Press: New York, 1981 [9] Dede, B.; Karipcin, F.; Cengiz, M. J. HazardMater 2009, 163(2–3), 1148. [10] K.C. Gupta, A.K. Sutar, J. Mol. Catal. A: Chem. 272 (2007) 64.

[11]Bagherzadeh, M.; Tahsini, L.; Latifi, R.; Amani, V.; Ellern, A.; Woo, L. K., Inorg. Chem. Commun., 2009, 12,

476 [12] Abbo, H. S.; Titinchi, S. J. J.; Prasad, R.; Chand, S., J. Mol. Catal. A: Chem., 2005, 225, 225

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Schiff base transition metal complexes are very

important chelates because of their cheap, easy synthesis and because of their chemical and thermal stability.

The central metal ion in these complexes acts as an

active site and thus effectively catalyzes chemical reactions.

Moreover,

these complexes have extensive applications in the fields of medicine, photo, magnetic chemistry, and electrochemistry[13].

[13]Bagherzadeh, M.; Tahsini, L.; Latifi, R.; Amani, V.; Ellern, A.; Woo, L. K., Inorg.

Chem. Commun., 2009, 12, 476

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Schiff base complexes of amino acids have gained importance

not only from the inorganic point of view but also because of their physiological and pharmacological activities. Biological activity of Schiff base amino acid complexes.

They act as good chelating agents [14] and behave as efficient

biologically active [15] and cytotoxic agents. In addition, Schiff base amino acids complexes are considered to constitute new kinds of potential antibacterial and anticancer reagents [16].

[14] El-Said, A. I.; Zidan, A. S. A.; El-Meligy, M. S.; Aly, A. A. M.; Mohammed, O. F. Transition Met Chem 2001, 26, 13. [15] Wang, Z.-M.; Lin, H.-K.; Zhu, S.-R.; Liu, T.-F.; Chen, Y.-T. J Inorg Biochem 2002, 89, 97. [16] Wang, M.-Z.; Meng, Z.-X.; Liu, B.-L.; Cai, G.-L.;Zhang, C.-L.; Wang, X.-Y. Inorg Chem Commun 2005, 8(4), 368.

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The complexes of Schiff bases synthesized from amino acids and

salicylaldehyde derivatives have gained remarkable attention because they are intermediates in many metabolic reactions[17]

Transamination
Decarboxylation
Elimination
Racemization, and C- C bond cleavage)

[17]- Nath, M.; Yadov, R. Bull Chem Soc Jpn 1997, 70, 131.[9 [18]Wang, M.-Z.; Meng, Z.-X.; Liu, B.-L.; Cai, G.-L.; Zhang, C.-L.; Wang, X.-Y., Inorg.

Chem. Commun., 2005
Decarboxylation and transamination reactions are important in the

biosynthesis of hormones, neurotransmitters, and pigments.

In addition amino acid Schiff base complexes are considered to

constitute new kinds of potential antibacterial and anticancer reagents[18]

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The condensation between the NH2 group of the

amino acid and the carbonyl group of the aldehyde or ketone is very difficult because of the Zwitterion effect, and the reaction needs special conditions.

It was found that the formation reaction of amino acid

Schiff bases is facilitated by the presence of the metal ion due to the formation of two five membered chelate rings, because in such a case the Schiff base is more planar[19].

[19] Nasser M. Hosny and Farid I. El-Dossoki, J. Chem. Eng. Data 2008, 53, 2567–2572

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It is known that a compound binding to a DNA in vitro can interact

with DNA in vivo to a certain extent, and the anticancer activities of a drug agent obtained both in vivo and in vitro are parallel to each

ther and have to be related to its interaction with DNA.
Studying the interaction between transition metal complexes and

DNA has attracted many interests[41-46] due to their importance in cancer therapy, design of new types of pharmaceutical molecules and molecular biology. On the other hand, few studies were carried out concerning the interaction of DNA with Schiff base amino acid complexes[47].

[41]Morrow, J.R., Inorg. Chem., 2000, 39, 2130. [42]Liu, C.; Wang, M.; Zhang, T.; Sun, H., Coord. Chem. Rev., 2004, 248, 147 [43]Wang, X.Y.; Zhang, J.; Li, K.; Jiang, N.; Chen, S.Y.; Lin, H.H.; Huang, Y.; Ma, L.J.; Yu, X.Q.,

Bioorg. Med. Chem., 2006, 14, 6745.

[44]Raman, N.; Fathima, S. S. A.; Raja, J. D., J. Serb. Chem. Soc., 2008, 73(11) [45]Mahalakshmi, N; Rajavel, R., Inter. J. Pharm. Techn., 2010, 2(4), 1133 [46]Zhang, Y.; Wang, X.; Ding, L., Nucleos. Nucleot. Nucl., 2011, 30, 49 [47]Erkkila, K. E.; Odom, D.T.; Barton, J. K., Chem. Rev., 1999, 99, 2777

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Design and spectroscopic characterization of some

Fe(II) base complexes.

The teratogenicity of the studied complexes was

tested on chick embryos.

Investigation of the interaction between the studied

complexes and DNA.

The antibacterial and antifungal activities have also

been performed against different strain of organism.

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Over view of results

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The suggested structures for the synthesized complexes

O OH N H2 O OH R N O OH R OH

+

HN AA H2L

N O OH R OH

H2L 2

Fe

2+

+

COO R H N O H N O H OOC Fe R H

Fe(HL)2

+ 2H+

HN + AA → H2L 2(H2L) + Fe2+ → Fe (HL)2 +2H+

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In case of histidine as amino acid H3L + Fe2+ → FeL + 3H+

where HN = 2-hydroxy-1-naphthaldehyde, AA = amino acid, H2L = Schiff base amino acid ligand, Fe(H2L)2 = nali, nphali, nasi, nari complexes and FeL = nhi complex.

N

HO

O N

H N

+ 2H+

FeHL

3

L + Fe2+ H

OH

N

O

O N

H N O

Fe

H2O

O H2

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Analysis Found (Calculated) Decom. temp. (oC) Molar conductance Λm (Ω-1 cm2 mol-1) Yield (%) Empirical Formula (Formula Weight) Comp. N H C 5.61 (5.76) 5.17 (5.39) 69.25 (69.12) 162 83 C14H13NO3 (243.254) nal 4.88 (4.86) 4.67 (4.90) 58.50 (58.34) 260 35.12 75 C28H28FeN2O8 (576.37) nali 4.45 (4.39) 5.21 (5.37) 75.35 (75.22) 170 85 C20H17NO3 (319.346) nphal 3.76 (3.94) 4.57 (4.82) 67.85 (67.61) >350 28.24 83 C40H34FeN2O7 (710.54) nphali 4.72 (4.88) 4.63 (4.56) 62.81 (62.73) 97 73 C15H13NO5 (287.168) nas 4.21 (4.33) 3.92 (4.05) 56.01 (55.74) 185 39.31 72 C30H26FeN2O11 (646.38) nasi 13.44 (13.59) 4.72 (4.89) 66.13 (66.01) 156 85 C17H15N3O3 (309.32) nh 9.58 (9.66) 4.72 (4.86) 46.83 (46.91) >350 47.61 81 C17H21FeN3O7 (435.22) nhi 17.21 (17.07) 6.05 (6.14) 62.29 (62.18) 133 86 C17H20N4O3 (328.37) nar 14.43 (14.66) 5.72 (5.80) 53.64 (53.40) 235 32.21 84 C34H44FeN8O9 (764.62) nari

Analytical and physical data of Schiff base amino acid ligands and their Fe(II) complexes.

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υ (Fe-O) υ (Fe-N) υ (C-O) phen υ COO-) asym υ (COO-) υ (-C=N) υ(OH); H2O Schiff base ligands and their complexe s _____ _____ 1362 (m) 1528 (w) 1413 (m) 1630 (s) 3403 (w) nal 490 (m) 552 (w) 1314 (m) 1548 (w) 1395 (m) 1622 (s) 3439 (m) nali _____ _____ 1326 (m) 1597 (m) 1405 (w) 1624 (s) 3466 (w) nphal 497 (m) 559 (w) 1315 (w) 1542 (w) 1394 (w) 1614 (s) 3440 (m) nphali _____ _____ 1319(m) 1590 (w) 1462(m) 1640 (s) 3440 (m) nas 482 (m) 550 (w) 1311(m) 1550 (w) 1404(w) 1629 (s) 3430 (m) nasi _____ _____ 1352 (m) 1531 (w) 1370 (m) 1626 (s) 3421 (m) nh 491(m) 563 (m) 1294 (w) 1537 (w) 1360 (m) 1610 (s) 3405 (w) nhi _____ _____ 1341 (w) 1577 (w) 1377 (m) 1639 (s) 3413 (w) nar 465(w) 553 (w) 1296 (m) 1537 (w) 1361 (w) 1630 (s) 3421(w) nari

The infrared absorption frequencies (cm-1)a of the investigated Schiff base amino acid ligands and their Fe(II)complexes.

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21 Molecular electronic spectra of (1) [nali] = 5x10-4 mol dm-3, (2) [nphali] = 2.5x10-4 mol dm-3, (3) [nasi] = 5.4x10-4 mol dm-3, (4) [nhi] = 5x10-4 mol dm-3, (5) [nari]=6x10-4 mol dm-3.

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22 The stoichiometry and the stability constants of the prepared complexes have been determined spectrophotometrically Continuous variation plots for the prepared complexes in aqueous-alcoholic mixture at [nali] = 3 × 10-3 M , [nphali] = 3 × 10-3 M, [nasi] =5× 10-3 M, [nhi] = 2× 10-3 M, [nari] = 1×10-3 M and 298 K.

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23 Molar ratio plots for the studied complexes in aqueous- alcoholic mixture at nali, nphali: [Fe2+] = 6 × 10-4 M; nasi: [Fe2+] = 1 × 10-3 M; nhi: [Fe2+] = 4 × 10-4 M; nari: [Fe2+] = 1 × 10-3 M and 298 K.

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24 The formation constant (Kf), stability constant (pK) and Gibbs free energy (ΔG) values of the prepared complexes in aqueous-ethanol at 298 K

ΔG kJ mol-1 pK Kf Type of complex Comple x

57.68

10.11 2.29 × 108 1:2 nali

55.44

9.89 1.12 × 1010 1:2 nphali

51.67

9.06 2.34 × 109 1:2 nasi

33.02

5.79 6.13 × 105 1:1 nhi

60.67

10.65 4.473 × 109 1:2 nari

nhi < nasi < nphali < nali < nari

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Dissociation curve of the prepared complexes in aqueous alcoholic mixture at [complex] = 5 × 10-3 M and 298 K.

Stability range of the investigated complexes

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Teratogenicity Test of the prepared complexes

Photographs of chick embryos exposed to 100 µg/ egg of the investigated complexes.

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28 Mean weight of chick embryos exposed to 100 µg/ egg of the investigated complexes.

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29 (a) Spectrophotometer titration of nali complex (10-3 M) in 0.01 M Tris buffer (pH 7.5, 25 °C) with CT-DNA (from top to bottom, 0-50 µM DNA, at 10 µM intervals). (b) Plot of [DNA]/(εa - εf) versus [DNA] for the titration

f DNA with nali complex.

300 400 500 600 700 0.0 0.5 1.0 1.5 2.0 2.5 3.0

1 2 3 4 5 6 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0

10

8[DNA]/

(a-f) 10

5[DNA]

(b) (a)

Fig. 7

nali+ DNA nali

Abs.

(nm)

DNA Binding Studies

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ΔG0 kJ mol-1 Binding Constant Kb×104 M-1 Type of chromism Chromism (%)a Δn (nm) λmax bound (nm) λmax free (nm) Complex

26.07

3.72 Hypo Hypo 10.30 16.06 4 26 512 372 516 346 nali

25.49

2.94 Hypo Hypo 9.11 16.19 6 34 516 384 522 350 nphali

25.93

3.51 Hypo Hyper 19.85 10.15 2 10 518 392 520 382 nasi

31.68

35.73 Hypo Hypo 9.25 14.53 4 21 514 384 518 363 nhi

27.27

6.02 Hypo Hypo 4.06 27.16 4 36 498 390 502 354 nari

Spectral parameters for DNA interaction with the prepared complexes

 

 

 

   

 

f b b f b f a

K DNA DNA            1

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31 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.

0.0 0.1 0.2 0.3 0.4 0.5 1.0 1.1 1.2 1.3 1.4 1.5 1.6

Fig. 8

[Complex]/ [DNA]



1/3

nhi nari nali nasi nphali EB

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Laila H. Abdel-Rahman, Rafat M. El-Khatib, Lobna A. E. Nassr and Ahmed M. Abu-Dief, J. Mol. Str. 2013, 1040, 9-18

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The main aim of the production and design of

any antimicrobial compound is to inhibit the causal microbe without any side effects on the patients.

In addition, it is worthy to stress here on the

basic idea of applying any chemotherapeutic agent which depends essentially on the specific control of only one biological function and not multiple ones.

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The chemotherapeutic agent affecting only one

function has a highly sounding application in the field of treatment by anticancer.

Most anticancer agents used in the present time

affect both cancerous diseased cells and healthy ones which in turns affect the general health of the patients.

Therefore, there is a real need for having a

chemotherapeutic agent which controls only one function.

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The

antibacterial screening results exhibited marked enhancement in activity on coordination with the metal ions against one or more testing bacterial strains.

This enhancement in the activity can be rationalized to the

basis of the structures of the ligands by possessing an additional azomethine (C=N) linkage which is important in elucidating the mechanism of transamination reaction in biological system.

The process of chelation increases the lipophilic nature of the

central metal atom, which in turn favors its permeation through the lipid layer of the membrane