Spectral, thermal, molecular modeling and biological studies on mono- and binuclear complexes derived from oxalo bis(2,3-butanedionehydrazone)

Background Hydrazones and their metal complexes were heavily studied due to their pharmacological applications such as antimicrobial, anticonvulsant analgesic, anti-inflammatory and anti-cancer agents. This work aims to synthesize and characterize novel complexes of VO2+, Co2+, Ni2+, Cu2+, Zn2+, Zr4+and Pd2+ ions with oxalo bis(2,3-butanedione-hydrazone). Single crystals of the ligand have been grown and analyzed. Results Oxalo bis(2,3-butanedionehydrazone) [OBH] has a monoclinic crystal with P 1 21/n 1 space group. The VO2+, Co2+, Ni2+, Cu2+, Zn2+, Zr4+ and Pd2+ complexes have the formulas: [VO(OBH–H)2]·H2O, [Co(OBH)2Cl]Cl·½EtOH, [Ni2(OBH)Cl4]·H2O·EtOH, [Cu(OBH)2Cl2]·2H2O, [Zn(OBH–H)2], [Zr(OBH)Cl4]·2H2O, and [Pd2(OBH)(H2O)2Cl4]·2H2O. All complexes are nonelectrolytes except [Co(OBH)2Cl]Cl·½EtOH. OBH ligates as: neutral tetradentate (NNOO) in the Ni2+ and Pd2+ complexes; neutral bidentate (OO) in [Co(OBH)2Cl]Cl·½EtOH, [Zr(OBH)Cl4]·2H2O and [Cu(OBH)2Cl2]·2H2O and monobasic bidentate (OO) in the Zn2+ and VO2+ complexes. The NMR (1H and 13C) spectra support these data. The results proved a tetrahedral for the Zn2+ complex; square-planar for Pd2+; mixed stereochemistry for Ni2+; square-pyramid for Co2+ and VO2+ and octahedral for Cu2+ and Zr4+ complexes. The TGA revealed the outer and inner solvents as well as the residual part. The molecular modeling of [Ni2(OBH)Cl4]·H2O·EtOH and [Co(OBH)2Cl]Cl·½EtOH are drawn and their molecular parameters proved that the presence of two metals stabilized the complex more than the mono metal. The complexes have variable activities against some bacteria and fungi. [Zr(OBH)Cl4]·2H2O has the highest activity. [Co(OBH)2Cl]Cl·½EtOH has more activity against Fusarium. Conclusion Oxalo bis(2,3-butanedionehydrazone) structure was proved by X-ray crystallography. It coordinates with some transition metal ions as neutral bidentate; mononegative bidentate and neutral tetradentate. The complexes have tetrahedral, square-planar and/or octahedral structures. The VO2+ and Co2+ complexes have square-pyramid structure. [Cu(OBH)2Cl2]·2H2O and [Ni2(OBH)Cl4]·H2O·EtOH decomposed to their oxides while [VO(OBH–H)2]·H2O to vanadium. The energies obtained from molecular modeling calculation for [Ni2(OBH)Cl4]·H2O·EtOH are less than those for [Co(OBH)2Cl]Cl·½EtOH indicating the two metals stabilized the complex more than mono metal. The Co(II) complex is polar molecule while the Ni(II) is non-polar. Graphical abstract Electronic supplementary material The online version of this article (doi:10.1186/s13065-015-0135-y) contains supplementary material, which is available to authorized users.


Synthesis of oxalo bis(2,3-butanedionehydrazone) [OBH]
OBH was prepared by heating under reflux a suspension (6 g, 0.05 mol) of oxalic acid dihydrazide in 50 mL EtOH and 8.6 ml (0.1 mol) of 2,3-butanedione on a heating mantle for 10 h. The precipitate thus formed was filtered off, recrystallized from ethanol and finally dried. It was characterized by elemental analysis and spectral studies. The 1 H NMR spectrum of the ligand showed signals at δ = 11.924 (s, 2H) and 2.129 (s, 6H) ppm for the NH and CH 3 protons. Its 13 C NMR showed peaks at 196.65, 167.58, 148.81 and 23.90 ppm for (C=O) ketonic (C=O) amidic , C=N and CH 3 , respectively.

Preparation of the metal complexes
The metal complexes were prepared by reacting calculated amounts corresponding to 2:1 ratio [M:L] in 50 mL EtOH and the mixture was heated under reflux for 6-8 h.
In the preparation of VO 2+ complex, 0.1 g of sodium acetate was added to raise the pH (~8) and precipitating the complex. The formed precipitates were filtered off, washed with hot water, hot ethanol and diethyl ether and finally dried in a vacuum desiccator over anhydrous silica gel. Attempts to grow single crystals for the complexes were done but unsuccessful. melting points were measured on a Griffin melting point apparatus. The conductance for 10 −3 mol L −1 DMSO solution of the compounds was measured on Orion 3 STAB Conductivity Bridge. The IR spectra were recorded as KBr discs on a FT/IR-6300 type A (400-4000 cm −1 ). The electronic spectra of the complexes were recorded on a Cary 5 UV-vis spectrophotometer, varian (200-900 nm). The 1 H NMR spectra of the ligand and the diamagnetic complexes were recorded in DMSO-d6, on a Bruker WP 200 SY Spectrometer (400 MHz) at room temperature using tetramethylsilane (TMS) as an external standard. The magnetic measurements were carried out on a Johnson-Matthey magnetic balance, UK. The TGA thermograms were recorded (25-800 °C) on a Shimadzu TGA-60; the nitrogen flow and heating rate were 50 ml/min and 10 °C min −1 , respectively. The X-ray single crystal diffraction data were collected on a Rigaku R-Axis Rapid diffractometer using filtered Mo-K α-radiation. The structure was solved by the direct methods and expanded using Fourier techniques at Kuwait University. The ligand and its complexes were investigated for antimicrobial activity against Bacillus, Aspergillus, Escherichia coli, Pennicillium and Fusarium as reported earlier [15]. All molecular calculations were carried out by HyperChem 7.51 software package. The molecular geometry of the Co 2+ and Ni 2+ complexes are first optimized at molecular mechanics (MM+) level. Semi empirical method PM3 is then used for optimizing the full geometry of the system using Polak-Ribiere (conjugate gradient) algorithm and Unrestricted Hartee-Fock (UHF) is employed keeping RMS gradient of 0.01 kcal/Å mol.

Crystal analysis of OBH
The crystal structure of OBH is shown in Structure 1. Its refinement data are summarized in Table 1 while the bond lengths and bond angles are presented in Table 2. OBH was crystalized as monoclinic system and P 121/n1 space group with molecular weight of 254.25. The N 1 -C 3 , O 1 -C 2 and O 2 -C 4 distances are 1.283(3), 1.210(3) and 1.206 Å, respectively, indicating true double bond; the amidic carbonyl has value slightly higher than the ketonic carbonyl. The N 2 -C 4 and N 1 -N 2 are 1.351(4) and 1.381 Å indicating single bonds. All bond angles are between 115 and 127 and 109.5° meaning the trigonal and tetrahedral geometries with sp 2 and sp 3 hybridization. The presence of lone pair of electrons on N 1 in C 3 N 1 N 2 reduces the angle from 120° to 115.7°. The bond angle of N 2 -C 4 -C 4 reduces to 110.6°, in consistent with some distortion, while that of O 2 -C 4 -N 2 increases to 126.9° due to the existence of two more electronegative atoms (O atoms).

Analytical data
The data of CHN and metal contents of the complexes are presented in Table 3 (Table 3) of 10 −3 mol L −1 DMSO solution proved the non-electrolytic nature. The measured value for the Co(II) complex supports the formation of [Co(OBH) 2 Cl] + Cl − ·½EtOH [18].

F (000) 268
Inspections of the IR spectral data of the complexes, O coordinating through the two amidic carbonyl groups based on the following observations: the υ(C=O) band observed at 1701 cm −1 in ligand spectrum was shifted to 1686-1699 cm −1 in complexes having little intensity indicating that the two amidic carbonyl groups (C=O amidic ) participated in bonding while the other two carbonyl (C=O ketonic ) still at the same position. The new band at 464-495 cm −1 is due to υ(M-O) vibration [19]. The υ(C=N) at 1605 cm −1 appeared very weak, less intensity with little shift to higher wavenumber in the Co(II) and Cu(II) complexes and to lower wavenumber in the Zr(IV) complex (1585 cm −1 ).
In the second mode, OBH acts as a mononegative bidentate in Zn 2+ and VO 2+ complexes coordinating through the two amidic carbonyl (enolic form), from each ligand molecule. The shift of υ(C=O) to lower or higher wavenumbers with appearance of υ(C=N)*, υ(C-O) (due to enolization of one amidic group) [20] and υ(M-O) at 1550, 1140 and 463 cm −1 indicates the participation of carbonyl group in bonding. In the VO 2+ complex, the band observed at 3412 cm −1 is attributed to hydrated water [21] and absence of sulfate bands indicates enol type of complexes. The 1 H NMR spectrum of [Zn(OBH-H) 2 ] showed splitting of NH signal as a result of conversion of one of NHC=O to N=C-OH and the existence of the others without participation (Structure 3). The signals of CH 3 protons appeared at the same position as in ligand spectrum. In its 13 C NMR, peaks of both ketonic and amidic groups still at the same position with appearance of a new one at 166.21 ppm although one of the C=O amidic changed to enol form. Also, the appearance of C=N as doublet peak in 149.44-148.44 ppm range confirming enolization. In the 13 C NMR spectrum      (Fig. 1b, c). The coordination sites are two azomethine nitrogens of the hydrazone moiety and two carbonyl groups of amidic moiety; each two donors chelated one metal ion. The shift of υ(C=N) to 1542 cm −1 and υ(C=O) amidic to 1644 in the Pd(II) complex and to 1552 and 1676 in the Ni(II) complex together with appearance of υ(M-N) [22] and υ(M-O) bands at ~465 and ~540 cm −1 , respectively. In the Ni(II) complex, the band of carbonyl groups splitted to two at 1697 and 1676 cm −1 ; the first is due to ketonic group which is not participated in bonding. The NH band appeared very weak in Ni(II) complex and very broad in Pd(II) complex. Finally, the band at 3389 or 3441 cm −1 in Ni(II) or Pd(II) complex is due to hydrated water or ethanol.

Mass spectra
The data of FAB-mass spectra of OBH and some of its complexes are shown in Table 3. The mass spectrum of OBH showed the molecular ion peak (base peak) at m/z = 255. 30  Moreover, the mass spectrum of [Ni 2 (OBH) Cl 4 ]·H 2 O·EtOH has a value of 371.7 (the base peak) corresponding to Ni(OBH)Cl·½EtOH meaning that this species is highly stable. Multi peaks were observed ending with one at 128.9 (intensity 65 %) due to ZrO 2 .

Magnetic moments and electronic spectra
The electronic spectral bands of the complexes as well as the magnetic moment values are presented in Table 6. The DMSO solutions of complexes have the same color as in the solid complexes. OBH exhibits one absorption band at 38,460 cm −1 collectively due to π → π* transitions of C=N, C=O ketonic and C=O amidic groups [23]. The broadness of the band may be due to existence of these groups in opposite sides. The two bands at 25,510 and 23,810 cm −1 in Cu(II) complex may be due to N → MCT and O → MCT [24]. The Ni(II) complex has only one band at 28,330 cm −1 due to N → MCT while Co(II) and Zr(IV) have also one band but at 23,320 and 22,830 cm −1 , respectively, due to O → MCT.   [25] having dsp 2 or dsp 3 hybridization. Evidence is electronic spectrum which showed one band at 15,250 cm −1 with molar extension coefficient of 94 mol −1 L. The spectrum resembled the spectra of the five-coordinate Co(II) complexes [26] and the square-pyramid is the suggested geometry.
The magnetic moment value, for each atom, in [Ni 2 (OBH-2H)Cl 4 ]·H 2 O·EtOH is 1.36 BM which is less than the normal values reported for tetrahedral or octahedral coordination containing two unpaired electrons. Its electronic spectrum showed a broad band at 19,050 cm −1 (ɛ = 180 mol −1 L) typical of a square-planar structure with some distortion [26] may be of tetrahedral; the anomalous magnetic value is consistent with mixed stereochemistry (square-planar + tetrahedral) around the two nickel ions [27]. On the other hand, the diamagnetic nature of [Pd 2 (OBH)(H 2 O) 2 Cl 4 ]·2H 2 O proved the square-pyramid structure in which the metal is surrounded by NO donors, two chloro and one coordinated water. The bands at 37,540 and 28,470 cm −1 are attributed to charge transfer transitions, probably O → Pd transition [28].
The electronic spectrum of [Cu(OBH) 2 Cl 2 ]·H 2 O exhibits one band with maximum at 20080 cm −1 assigned to the 2 E 2g → 2 T 2g transition in an octahedral geometry [29]. The band is broad due to the Jhan-Teller effect which enhances the distortion of the octahedral geometry generally important for odd number occupancy of the e g level. The magnetic moment value (1.45 BM) was found lower than the values reported for the d 9 -system containing one unpaired electron (1.73-2.25 BM) suggesting interactions between the copper centers.

Thermal analysis
The decomposition steps, the DTG maximum temperature and the removing species are shown in Table 7. The thermogram of [Co(OBH) 2 Cl]Cl·½EtOH showed three decomposition steps at mid-points of 60, 319 and 500 °C corresponding to the removal of ½Cl 2 + ½EtOH (Found 6.36 %; Calcd. 8.84 %); C 16   Cl·½EtOH indicating that the presence of two metals stabilized the complex more than the mono metal lowering the energy. The dipole moment calculated for the Co(II) complex is 4.949 D proving the polar nature of the complex. The value of Ni(II) complex is 0.413 D indicating its non-polarity.

Biological activity
The antimicrobial activity of the metal complexes depends on the following factors: the chelate effect, i.e., bidentate ligands show higher antimicrobial activity than monodentate; the nature of the ligands; the total charge of the complex: cationic > neutral > anionic; the nature of the counter ion and the nuclearity of the metal center: binuclear are more active than mononuclear ones. It depends more on the metal center itself than on the geometry around the metal ion.
The antimicrobial activities of OBH and its complexes are examined against Bacillus, E. coli, Aspergillus,  Penicillium and Fusarium and the data are given in Table 9. The data showed that [Zr(OBH)Cl 4 ]·2H 2 O has higher activity against all tested microorganisms except E. coli. The activity is highest and more with Penicillium (9 mm zone inhibition). The higher activity may be due the presence of non-ionizable chlorine and to the less planarity of the complex making it more lipophilic. Most compounds have high activity against Fusarium.
[Cu(OBH) 2 Cl 2 ]·2H 2 O has higher value against Fusarium (15 mm). Comparing these data with that of ampicillin and those obtained for different hydrazone complexes showed more or less activity [29,30].

Further materials
Crystallographic data for the structure reported in this paper have been deposited with Cambridge Crystallographic Data Center as supplementary publication CCDC-985982.