Synthesis, crystal structure, characterization and biological activity of 2,5-hexanedione bis(isonicotinylhydrazone) and N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide complexes

Article abstract of DOI:10.1016/j.saa.2015.05.071

The reaction between 2,5-hexanedione and isonicotinic acid hydrazide in EtOH gave two products. The ethanol insoluble product was identified as 2,5-hexanedione bis(isonicotinylhydrazone) [HINH] and the soluble ethanol product as N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide [DINA]. A series of Cr³⁺, Fe³⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Hg²⁺ and Pd²⁺ complexes of HINH and Co²⁺, Cu²⁺, Zn²⁺ and Hg²⁺ complexes of DINA have been synthesized and structurally characterized. Based on the elemental analysis, mass spectra and molar conductance, the complexes have assigned the proposed imperical formulae. The crystal structures of N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide and its Zn²⁺ and Hg²⁺ complexes have been solved by X-ray diffraction having [Zn(DINA)₂Cl₂] and [Hg(DINA)₂Cl₂] in a tetrahedral structure. In the DINH complexes, the ligand coordinates as a monodentate through the pyridine nitrogen. On the other hand, HINH behaves as a tetradentate (neutral or binegative) manner with the two metal ions. The magnetic moments and electronic spectra of all complexes provide tetrahedral, square-planar, trigonal biyramid and/or octahedral structure. The thermal decomposition of the complexes revealed the outer and inner solvents as well as the end product. The steady part of [Zn(DINA)₂Cl₂] and [Hg(DINA)₂Cl₂] thermograms till 303 and 286 °C indicates the absence of any outside solvents. All compounds have activity against bacteria more than fungi. [Cd₄(HINH)Cl₈]·3H₂O has the highest values.

Full text of DOI:10.1016/j.saa.2015.05.071

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Accepted Manuscript
Synthesis, crystal structure, characterization and biological activity of 2,5-hex-
anedione bis(isonicotinylhydrazone) and N-(2,5-dimethyl-1H-pyrrol-1-yl)iso-
nicotinamide complexes
Bakir Jeragh, Mayada S. Ali, Ahmed A. El-Asmy
PII:
S1386-1425(15)00684-8
http://dx.doi.org/10.1016/j.saa.2015.05.071
SAA 13739
DOI:
Reference:
Spectrochimica Acta Part A: Molecular and Biomo-
lecular Spectroscopy
To appear in:
Received Date:
Revised Date:
Accepted Date:
1 February 2015
3 May 2015
23 May 2015
Please cite this article as: B. Jeragh, M.S. Ali, A.A. El-Asmy, Synthesis, crystal structure, characterization and
biological activity of 2,5-hexanedione bis(isonicotinylhydrazone) and N-(2,5-dimethyl-1H-pyrrol-1-
yl)isonicotinamide complexes, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2015), doi:
http://dx.doi.org/10.1016/j.saa.2015.05.071
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Synthesis, crystal structure, characterization and biological activity
of 2,5-hexanedione bis(isonicotinylhydrazone) and N-(2,5-dimethyl-
1H-pyrrol-1-yl)isonicotinamide complexes
Bakir Jeragh, Mayada S. Ali, Ahmed A. El-Asmy*
Chemistry Department, Faculty of Science, Kuwait University, Kuwait
Abstract
The reaction between 2,5-hexanedione and isonicotinic acid hydrazide in EtOH gave two
products. The ethanol insoluble product was identified as 2,5-hexanedione
bis(isonicotinylhydrazone) [HINH] and the soluble ethanol product as N-(2,5-dimethyl-1H-
pyrrol-1-yl)isonicotinamide [DINA]. A series of Cr3+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+
and Pd2+ complexes of HINH and Co2+, Cu2+, Zn2+ and Hg2+ complexes of DINA have been
synthesized and structurally characterized. Based on the elemental analysis, mass spectra and
molar conductance, the complexes have assigned the proposed imperical formulae. The crystal
structures of N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide and its Zn2+ and Hg2+ complexes
have been solved by X-ray diffraction having [Zn(DINA)2Cl2] and [Hg(DINA)2Cl2] in a
tetrahedral structure. In the DINH complexes, the ligand coordinates as a monodentate through
the pyridine nitrogen. On the other hand, HINH behaves as a tetradentate (neutral or binegative)
manner with the two metal ions. The magnetic moments and electronic spectra of all complexes
provide tetrahedral, square-planar, trigonal biyramid and/or octahedral structure. The thermal
decomposition of the complexes revealed the outer and inner solvents as well as the end product.
o
The steady part of [Zn(DINA)2Cl2] and [Hg(DINA)2Cl2] thermograms till 303 and 286 C
indicates the absence of any outside solvents. All compounds have activity against bacteria more
than fungi. [Cd4(HINH)Cl8].3H2O has the highest values.
Keywords: 2,5-Hexanedione bis(isonicotinylhydrazone); N-(2,5-Dimethyl-1H-pyrrol-1-yl)iso-
nicotinamide; Biological activity; x-ray crystallography
_________________________________
Corresponding author, Tel.: +96566734989.
E.mail address: aelasmy@yahoo.com

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Introduction
A number of hydrazone derivatives have been developed and evaluated for their antibacterial
activity. Also, their metal complexes have antimicrobial and antitumor activity due to the ability
of the ligands to coordinate with the metal ions needed in the metabolism of fungus. Liu et al.
synthesized and evaluated acetyl hydrazone derivatives for antitumor activity against A549,
HCT11b, HepG2, PC-9 and A375 cell lines with an IC50 value of 4-17 µM. Aryl hydrazone
derivatives synthesized by Vogel et al.were reported to have an IC50 of 6.7 nM against MDA-MB
231 and MCF-7 breast cancer cell lines [1]. Mono- and polynuclear Schiff base complexes were
used as oxidants serving as models for galactose oxidase. The Cu(II) model has a special interest
in some biological systems [2]. Much interest has been focused on the hydrazone complexes to
show the coordinative behavior- antimicrobial activity relationship. Some hydrazones and their
complexes have antitumor activity [3]: oximinohydrazones as antiparasitic, fungicidal and
bactericidal properties [4]. Compounds containing oxime and amino groups were used for the
separation and determination of some transition metal ions [5]. Aromatic heterocycles containing
nitrogen act as ligands toward some metal ions [6]. Pyrroles belong to this class and are five-
membered heterocyclic ligands containing nitrogen. They have a considerable attention due to
their applicability in medicine [7–9] as antitumor, anti-inflammation, antipyretic, antiviral,
antimicrobial, anticonvulsant, antihistaminic, antidepressant, insecticides, and fungicides [10-16].
In coordination chemistry, nitrogen ligands exhibit various coordination modes and have received
considerable attention for the synthesis of transition metal complexes with various nuclear ties
[17]. Complexes of some transition metal ions with 2-acetylpyridineisonicotinyl, pyrrolyl-2-
carboxaldehydeisonicotinyl, 2,5-dihydroxyacetophenoneisonicotinoyl, isonicotinamidofurfur-
aldimine, 2-thiophenecarbonyl and isonicotinoylhydrazones of 3-(N-methyl)isatin were reported
[18-21].
On continuation to the work done on 2,5-hexanedione bis(isonicotinylhydrazone) as well
as its metal complexes [22], the aim is to synthesize and characterize new keto-form complexes in
which the method of preparation and conditions are changed. Also, the formation of N-(2,5-
dimethyl-1H-pyrrol-1-yl)isonicotinamide during the preparation of the parent one in crystalline
form pushed us to prepare its complexes.

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Experimental
Reagents
The starting materials, CrCl3.3H2O, VOSO4.H2O, FeCl3.3H2O, CoCl2.6H2O, NiCl2.6H2O,
CuCl2.2H2O, ZnCl2.2H2O, CdCl2.2H2O, HgCl2, K2PdCl4 and ZrCl4, isonicotinic acid hydrazide,
2,5-hexanedione and solvents used for the synthesis of ligands and complexes were Sigma
Chemicals and used as received.
Synthesis of HINH and DINH
HINH was prepared similar to our previous work [22]. On evaporating the mother liquor to its
half volume, the precipitate formed was separated by filtration, recrystallized from ethanol and
dried. It was confirmed as N-(2,5-dimethyl-1H-pyrrol-1yl)isonicotinamide (DINH) using
elemental analysis, spectra (IR, NMR and MS) and single crystal structure (Structure 1).
Structure 1. N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide (DINA)
Synthesis of the metal complexes of HINH
The complexes were prepared by heating a mixture of HINH (3 mmol), dissolved in 20 mL
ethanol and the metal salt (3 mmol) in 30 mL ethanol on a water bath for 1h. The binuclear
complexes were prepared by heating a mixture of the ligand (3 mmol) dissolved in 20 mL
ethanol and the metal salt (6 mmol) in 30 mL ethanol solution (v/v) under reflux on a water bath
for 4 - 6 h. The precipitate was filtered off, washed with diethyl ether and finally dried in a
vacuum desiccator over silica gel.