# Nickel(II) Complexes of Hydrazone of  Isoniazid and Their Magneto-Spectral, Electrochemical,  Thermal and Antimicrobial Investigations

Authors: Surendra Prasad; Ram K. Agarwal
Journal: Research Letters in Inorganic Chemistry
 (2008)

---

## Abstract

The synthesis of novel nickel(II) complexes with new ligand derived from hydrazone of isoniazid has been reported. The complexes have general compositions[Ni(L)2X2] or [Ni(L)3](ClO4)2, where L = N-isonicotinamido-furfuraldimine (INH-FFL) and X=Cl− or NCS−. The ligand hydrazone behaves as neutral bidentate (N and O donor) through the carbonyl oxygen and azomethine nitrogen. On the basis of elemental analysis, molecular weight determinations, magnetic susceptibility/moment, thermogravimetric, electrochemical, and spectroscopic studies, the new complexes have been characterized with octahedral geometry. The antibacterial and antifungal studies of the present complexes show that they are moderate antibacterial and antifungal agents.


---

## Body

## 1. Introduction

The  synthesis of  transition metal complexes with Schiff bases
of nitrogen and oxygen donor has stimulated interest due to their vast variety
of biological activities ranging from pharmacological, antitumour, fungicide,
bactericide, anti-inflammatory, and antiviral activities [1, 2]. We have
recently published some lanthanide(III)
complexes of semicarbazones [3] and oxovanadium(IV) [4, 5], platinum(II)
[6], cobalt(II), and nickel(II) [2, 7] complexes of thiosemicarbazones derived
from 4-aminoantipyrine. The antibacterial and antifungal properties of the
thiosemicarbazone ligands and their cobalt(II) [2, 7], nickel(II) [7], and oxovanadium(IV) [5]
complexes have also been examined. In continuation of our work on hydrazones of
isoniazid (a drug of proven therapeutical importance [8]) complexes of metal
ions [9], the present work describes the synthesis, magneto-spectral, electrochemical, thermal, and biological studies
of a novel series of Ni(II) complexes of N-isonicotinamido-furfuraldimine (INH-FFL) (Figure 1).Figure 1
N-Isonicotinamido-furfuraldimine (INH–FFL)


## 2. Experimental

The nickel(II) salt,NiCl2⋅6H2O, was
obtained from BDH and used as received. Ni(NCS)2 and Ni(ClO4)2 were prepared by methods reported elsewhere [7]. The hydrazone of isoniazid viz. INH-FFL was synthesized by following a general method reported by us [9] (yield ca. 80%). A general method was used
for the synthesis of the nickel(II) complexes [7]. A hot ethanolic solution of
the corresponding nickel(II) salt was mixed with a hot ethanolic solution of
the hydrazone ligand in molar ratio 1:2, and 1:3 for [Ni(L)2X2] and [Ni(L)3](ClO4)2 complexes, respectively.
The reaction mixture was refluxed on a water bath for ~2 hours. On cooling the
reaction mixture at room temperature, the colored complexes precipitated out in
each case. The complexes were filtered out, recrystallized, washed with ethanol,
and dried over P4O10 under vacuum.The
molecular weight of the complexes was determined cryoscopically using  Beckmann thermometer. The nickel contents of
the complexes were determined complexometrically after decomposing with conc.H2SO4 and H2O2 [7], while the chlorine was estimated by
reported method [10]. The thiocyanate was estimated argentometrically. The perchlorate was estimated by the
method reported in our previous work [7]. The percentage of nitrogen was
determined by Kjeldahl method. The conductivity and the magnetic measurements
of the complexes were performed using a Toshniwal conductivity bridge and Evans
magnetic balance, respectively [2, 7]. The infrared spectra and diffused reflectance
spectra of the solid complexes were recorded on a Perkin Elmer FT-IR infrared
spectrophotometer model 521 and Beckmann DK-2A spectrophotometer, respectively.
Thermogravimetric analyses of the complexes were performed on Perkin Elmer
Pyris Diamond in static air with unlidded small platinum boat sample holder at
heating rate 6C°min−1. The antibacterial and antifungal activities
of the representative nickel(II) complexes and standard drugs (ampicillin and
tetracycline) were screened using reported methods [2].


## 3. Results and Discussion

The reaction of nickel(II) salts with INH-FFL resulted in the
formation of[NiX2(L)n], where X=Cl− or NCS−,  n=2, and [Ni(L)n]X2,
while X=ClO4−, n=3. The analytical data, molar
conductance in nitrobenzene, and molecular weights of the complexes are
presented in Table 1. The complexes were quite stable and could be stored for
several weeks without any appreciable change but decomposed on heating beyond
250C°. The paramagnetism observed for the present complexes ranges from 3.1–3.2 BM (Table 1)
and is consistent with the octahedral stereochemistry [7].Table 1
Analytical, conductivity, molecular weight, and magnetic
moment data of nickel(II) complexes of hydrazones of isoniazid.
ComplexYield (%)Analysis: found (calcd.) (%)m.wt. found (Calcd.)Ωm(ohm−1cm2mole−1)μeff (BM)NiCHNAnion[NiCl2(INH‐FFL)2]7210.4747.003.1814.9012.555553.13.1(10.53)(47.14)(3.21)(15.00)(12.67)(560)[Ni(NCS)2(INH‐FFL)2]689.6947.482.9318.4519.066003.33.2(9.75)(47.60)(2.97)(18.51)(19.17)(605)[Ni(INH‐FFL)3](CIO4)2656.4843.732.9613.8921.8989951.83.2(6.53)(43.85)(2.99)(13.95)(22.03)(903)The
infrared frequencies in the present ligand associated with amide group
(carbonyl-oxygen), azomethine-nitrogen (C=N), and heterocyclic nitrogen are
expected to be influenced on complex formation with nickel(II). Generally,
amides show two absorption bands: (i) the carbonyl absorption band near 1640cm−1 (amide-I
band) and (ii) strong band in the 1600-1500cm−1 region
(amide-II band). The amide-I band in INH-derivatives, however, appeared at 1655cm−1 [11]. In
the infrared spectra of the complexes, a considerable negative shift in v(C=O) was observed indicating a decrease in the
stretching force constant of (C=O) as a consequence of coordination through the
carbonyl oxygen atom of the ligand. Another important band occurs at 1585cm−1 range is
attributed to v(C=N) (azomethine) mode [12]. In spectra of all
the complexes, this band is shifted to lower wave number and appears in 1545-1535cm−1 region
indicating the involvement of N-atom of the azomethine group in coordination
[12]. The overall infrared spectral evidence suggests that the present ligand
acts as bidentate ligand and coordinates through amide oxygen and azomethine nitrogen
atoms forming a five-membered chelate ring.
The three fundamental absorptions in [Ni(NCS)2(L)2] complex, that is, C–N stretching (v1), C–S stretching (v3), and N–C–S bending (v2) identified at 2040-2035, 845-830,
and 470-465cm−1 region
are associated with the terminal N-bonded isothiocyanate ions [7]. In the
perchlorato complex, the presence of the v3(1100-1090cm−1) and v4(625-620cm−1) bands
indicates that the Td symmetry of ClO4− is
maintained in the complex. It suggests the presence of ClO4− outside
the coordination sphere [13].The electronic spectra of the
octahedral nickel(II) complexes exhibit spectra showing three spin-allowed
transitions in 7000–11000cm−1(v1), 15000–19000cm−1(v2), and 25000–29000cm−1(v3) regions [2, 7]. In the present
complexes, the electronic spectra were very similar to each other and consist
of bands in 8200–10930 {v1,A2g3(F)→T2g3(F)},
17540–17700 {v2,T1g4(F)→A2g4(F)}, and
26950–27500cm−1{v3,T1g4(F)→T1g4(P)} regions,
which clearly indicated the octahedral stereochemistry of the complexes.The thermogravimetric results
of representative complexes clearly suggested the absence of any water molecule
in the complexes. During 160–265C° temperature
range, the weight loss corresponds to 37.21–39.34% indicates
the loss of one molecule of INH-FFL, while second ligand molecule evaporated
off at ~400C°. Finally, at ~600C°, NiO formation takes place according to the
following general equation: (1)[Ni(INH‐FFL)2Cl2]→175–265C°[Ni(INH‐FFL)Cl2]→325–400C°[NiCl2]→515–600C°NiO. The antibacterial activities of the
nickel(II) complexes and standard drugs (ampicillin and tetracycline) were
screened by agar cup method in DMF solvent at a concentration of 50μg/mL under identical conditions. The results
were checked against gram positive bacteria, Bacillus subtilis and Staphylococcus
aureus, and gram negative bacteria, Escherichia coli and Salmonella
typhi, which show that the nickel(II) complexes of INH-FFL have moderate
antibacterial activities against these bacteria (Table 2). The screened
antifungal activities of the complexes against two fungi (Aspergillus niger and Candida albicans) show that they are less active compared to
salicylic acid and appear to be moderate antifungal agents (Table 2). The
antibacterial and antifungal activities of the present complexes were also
compared with the activity results of some other nickel(II) complexes having
different ligands (Table 2) [14–17]. It was found
that the present complexes are less potent bactericides with respect to few
reported nickel(II) complexes [14, 15], while some
other complexes have almost comparable [16, 17] or less [17] antibacterial and
antifungal activities. However, the experimental conditions for complexes
reported in literature are different [14–17].Table 2
Antifungal
and antibacterial activities of nickel(II) complexes of INH-FFL and their
comparison with the activity results of some other reported nickel(II)
complexes [14–17].
ComplexAntibacterial activityZone of inhibition in numbersAntifungal actionB.s.S.a.E.c.S.t.A. nigerC. albicaus[Ni(INH‐FFL)2Cl2]1210109++++[Ni(INH‐FFL)2(NCS)2]16151514++++++[Ni(INH‐FFL)3](CIO4)213111211++++Ampicillin24221716——Tetracycline18172122——Salicylic acid————++++++++[Ni(HIBN)Cl] [14]—3840———Ni2L1 [15]—1818———Ni2L2 [15]—2021———[Ni(Pr–BIAN)2](CIO4)2 [16]na1418———[Ni(cyclam)(2-napthoata)2] [17]7777++++++[Ni(cyclam)(3-nitrobenzoata)2] [17]1412nana++HIBN:
2-hydroxy-1-naphthaldehyde)-3-isatin]-bishydrazone
L1: 4-methyl-2,6-di-formylphenol
L2: 4-t-butyl-2,6-di-formylphenol
Pr–BIAN:bis[N-(2,6-diisopropylphenyl)imino]acenaphthene
na: No
activityThe overall experimental
evidences thus show that the studied nickel(II) complexes,[Ni(L)2X2] and [Ni(L)3](ClO4)2, display a coordination
number six and have an octahedral environment around the metal ion. The complexes appear to be moderate
antibacterial and antifungal agents.



---

*Source: 350921-2008-12-01.xml*