Synthesis, Physicochemical Studies and Biological Properties of Mixed-Ligand Nickel(II) Complexes Containing β-Diketones With N-donor Ligands

Some mixed ligand nickel(II) complexes of thenoyltrifluoroacetone (tta-H) with 2,2ꞌ-bipyridine (bipy), 1,10-phenanthroline (phen) and tetramethylethylenediamine (tmen) [Ni(tta)(N-N)(NO3)]; N-N= bipy, phen, or tmen] have been synthesized and characterized by molar conductance measurements, elemental analysis, mass spectrometry, spectral measurements and antimicrobial activities. Attempt to prepare the mixed ligand nickel(II) complexes containing acetylacetone (acacH), benzoylacetone (bzacH), dibenzoylmethane (dbm-H) and thenoyltrifluoroacetone (tta-H) with ethylenediamine associated with NO3 counter ion led to the formation of [Ni(β-diketone)2en]. The β-diketones enolized acting as bidentate ligand, coordinating to the metal with carbonyl and enolic oxygen, ethylenediamine (en) coordinates to the metal using N, N chromophores. The nickel complexes of the type [Ni(tta)(N-N)NO3)] are five-coordinate square pyramidal in geometry while those of the type [Ni(β-diketone)2en] are six-coordinate octahedral geometry. The conductivity measurement in nitromethane revealed that the [Ni(tta)(N-N)NO3)] complexes are non-electrolyte. The complexes were screened for their in-vitro antimicrobial activity against six microorganisms. A comparison of the complexes with gentamicin showed that most of the complexes are resistant to tested organisms except [Ni(tta)2(en)].H2O, [Ni(bzac)2(en)] and [Ni(bta)2(en)] which compared favourably well in Staphylococcus aureus.


Introduction
There has been growing interest in the metal derivatives of β-diketones during the past two decades and a lot of articles have been published on the synthesis of these metal complexes (Ahumada et al., 2018;Omoregie et al., 2017;Omoregie et al., 2016;Omoregie, 2014;Omoregie, 2012;Arpita and Raman, 2010).Metal complexes of β-diketones are being focused on in medicinal chemistry and research has revealed that anticancer activity against tumoral cells is exhibited by Platinum(II) complexes of β-diketones (Wilson and Lippard, 2012).
Extensive literature is available on the application of β-diketonate complexes in catalysis and as precursors for MOCVD (Bose et al., 2016;Poncelet et al., 2005;Lassahn et al., 2005;Nable et al., 2003.).Studies revealed that β-diketones were used in the design of many luminescence compounds (Ahumada et al., 2018) and the metal complexes were used to inhibit the growth of K562 cell (Almeida et al., 2015).
Mixed-ligand nickel(II) complexes containing acac and bzac have been synthesized but there is no report on the synthesis and biological activity of the [Ni(tta)(N-N)(NO 3 )] and ethylenediamine series.Hence the need to synthesize the mixed-ligand complexes in ratio 1 of β-diketone to 1 of 2,2′-bipyridine, 1,10-phenanthroline, ethylenediamine/tetramethylethylenediamine and investigate their antimicrobial activity.In the process of synthesizing these, ratio 2 of β-diketone and 1 of ethylenediamine were formed.

Antimicrobial Susceptibility Testing
The antimicrobial activity of the complexes prepared was determined by agar cup diffusion method using each compound in decreasing concentration of 200 mg/mL-6.25 mg/mL dissolved in methanol against isolated organisms.Plate cultures were prepared either by seeding (bacteria/fungi) or spreading using 0.1 mL of 10 -2 dilution from 18-12 hours.3 drops of dissolved compound was used to fill each of the well dug in the set agar media, pre-incubation diffusion period of 1 hour on bench was observed.Incubation of the cultured plates were observed at 37 C for 24 hours (for bacteria) and 28  C for 24-72 hours (for fungi).Observation of the plates for zones of growth inhibition, measured in mm was recorded (Omoregie et al., 2015).

Physical Measurements
The elemental analysis for CHNS were determined at the School of Chemistry and Physics, University of KwaZulu-Natal, South Africa.The percentage metal in the nickel(II) compounds were determined titrimetrically using EDTA.The magnetic susceptibilities of the compounds at room temperature were measured using the Sherwood magnetic susceptibility balance.
The infrared spectra were measured using nujol on Perkin Elmer spectrophotometer 11 FT-IR.The electronic spectra of the compounds in chloroform were recorded on a Perkin Elmer Lambda Double Beam UV/VIS spectrophotometer using 1cm glass cell at the Department of Chemistry, University of Ibadan, Ibadan, Nigeria.

Results and Discussion
The formation of the complexes were confirmed by microanalysis.Scheme 1 is for the formation of [Ni(tta)(N-N)NO 3 )] series while [Ni(β-diketone) 2 en] complexes are formed using scheme 2.
The analytical data, colours, percentage yields, melting points, molar conductivities, and room temperature magnetic moments of the complexes are presented in Table 1.The molar conductivities of the [Ni(tta)(N-N)NO 3 )] complexes in nitromethane were in the range 23-53 ohm -1 cm 2 mole -1 , showing that they are non-electrolytes.A value of 60-115 ohm -1 cm 2 mole -1 is expected for a 1:1 electrolyte (Geary, 1970)

Electronic Spectra, Magnetic Moment and Mass Spectroscopy
The electronic spectra of the nickel complexes in chloroform are presented in Table 3.There is a clear relationship between five coordinate high spin square pyramidal complexes and tetragonal six coordinate complexes through removal of one ligand from an octahedral complexes (Lever, 1986).Bands similar to octahedral complexes were observed in the [Ni(tta)(bipy)(NO 3 )], [Ni(tta)(phen)(NO 3 )] and [Ni(tta)(tmen)(NO 3 )] and are tentatively square pyramidal in geometry (Lever, 1986).This is supported by the X-ray structure of [Ni(bta)(phen)(Cl)] (Omoregie, 2018).The [Ni(β-diketone) 2 en] series had absorption bands typical of six-coordinate octahedral geometry which is corroborated by the observed magnetic moment.
The peak observed at m/z 435 corresponded to [Ni(tta)(bipy)] + and this shows that NO 3 has been lost.

Antimicrobial Activities
The ligands showed good activity at 200 mg/mL in the tested bacteria except in Klebsiella pneumonia in which bta-H and bza-H showed resistance and moderate activity respectively.dbm-H showed pronounced activity in all the tested bacteria while tta-H only showed sensitivity in E-coli.But it had moderate sensitivity in Staphylococcus aureus ; Bacillius subtilis and Salmonella enterica.All the nickel complexes showed good activity in Staphylococcus aureus except [Ni(tta)(bipy)(NO 3 )] and [Ni(tta)(phen)(NO 3 )] that were resistant and [Ni(dbm) 2 (en)]H 2 O showed moderate activity.All the complexes were resistant in Klebsiella pneumonia except [Ni(tta) 2 (en)].H 2 O and [Ni(bzac) 2 (en)] which were moderately sensitive and sensitive respectively.The complexes were also resistant in Escherichia coli except [Ni(bzac) 2 (en)] and [Ni(bta) 2 (en)] with moderate sensitivity.Comparison of the ligands with the standard drug (Tioconazole) showed that the ligands have mild antifungi properties.[Ni(bzac) 2 (en)] and [Ni(bta) 2 (en)] compared favourably well with Tioconazole while [Ni(tta) 2 (en)] and [Ni(dbm) 2 (en)] H 2 O were resistant.There is a good comparison of the ligands with the gentamicin except tta-H which was mild.Comparison of the complexes with gentamicin showed that most of the complexes are resistant except [Ni(tta) 2 (en)].H 2 O, [Ni(bzac) 2 (en)] and [Ni(bta) 2 (en)] which compared favourably well in Staphylococcus aureus.

Conclusion
A tentative five-coordinate square pyramidal geometry is proposed for the [Ni(tta)(NN)(NO 3 )] complexes while the [Ni(β-diketone) 2 en] series have probable six-coordinate octahedral geometry.This is corroborated by magnetic, infrared and electronic spectral measurements.The antibacterial studies revealed that [Ni(bzac) 2 (en)] shows a broad spectrum of antimicrobial activity against Staphylococcus aureus, Klebsiella pneumonia, Escherichia coli, Candida albicans, Aspergillus niger and Penicillium notatum.A similar trend is observed in the antimicrobial activity of [Ni(tta)(bipy)(NO 3 )] and [Ni(tta)(phen)(NO 3 )] which shows that the antimicrobial activity is not affected by the presence of any substituent as compared with [Ni(tta) 2 (en)].

Table 1 .
Analytical and physical data of mixed ligand nickel(II) complexes Key: vs = very strong, s = strong, m = medium, b = Broad, w=weak Table3.Electronic spectral data of mixed-ligand nickel(II) complexes