An N4-Tetradentate Hydrazone Ligand That Binds in a Neutral, Mono- and Bisdeprotonated Form to Iron(II) and Zinc(II) Metal Ions

The coordination chemistry of butane-2,3-dione bis (2′-pyridylhydrazone) towards the divalent first-row transition metals zinc and iron has been explored. Depending upon the conditions, the ligand in the six complexes was found to be either neutral, mono, or doubly deprotonated. The zinc(II) and iron(II) complexes were fully characterized by elemental analysis, mass spectrometry, and X-ray diffraction methods.


Introduction
A great interest has been devoted towards the coordination chemistry of first-row transition metal complexes containing organic chelating ligands. Particularly, coordination complexes play a significant role in numerous biological functions, which has led to intensive studies in the field of bioinorganic chemistry [1][2][3]. Coordination compounds are fundamental in biological systems such as energy storage, oxygen transport, the proper functioning of different enzymes, electron transfer, and selective oxidation of carbonhydrogen bonds, nitrogen fixation, and photosynthesis [4][5][6]. Over the past two decades, tremendous efforts have been devoted to the development of various types of supporting ligands and their metal complexes in order to model and mimic the biological systems. Iron and zinc have been found in the active sites of metalloenzymes; they catalyze a wide range of chemical reactions. Specifically, the chemistry of mono and binuclear iron(II) and zinc(II) metal complexes has aroused considerable interest in their use as model complexes as well as their biomedical applications [7][8][9][10][11][12].
Schiff bases continue to occupy an important position as ligands in metal coordination chemistry, even after more than a century since their discovery [13][14][15][16][17][18][19]. Schiff bases have played a key role as chelating and widely used ligands in main group and transition metal coordination chemistry due to their ease of synthesis, stability under a variety of oxidative and reductive conditions, and the structural versatility associated with their diverse applications [20][21][22][23][24][25]. A large number of Schiff bases and their metal complexes have been studied for their interesting and important properties, for example, their catalytic activity [26-32], photochromic properties [33], and use as potential antitumor drugs [34][35][36].
The earliest studies relevant to our work are those by Lions and co-workers, who reported the formation of cationic complexes from neutral ligands. The cationic complexes could be deprotonated, yielding neutral complexes for metals in oxidation state +II (Scheme 1) [37]. Working with butane-2,3-dione bis (2 ′ -pyridylhydrazone), the same group described the synthesis of deprotonated complexes using 5 M sodium hydroxide [38]. Furthermore, Bailey et al. published work on the doubly deprotonated binuclear nickel complexes and their electrochemical characterization [39,40]. In 2017, Naskar et al. reported on butane-2,3-dione bis (2 ′ -pyridylhydrazone) and hexane-3,4-dione bis (2 ′ -pyridylhydrazone) based copper(II) complexes [41]. Based on the very few earlier reports on the neutral N4 donor ligands and their coordination towards the transition metals, we turned our attention towards the synthesis of stable butane-2,3-dione bis (2 ′ -pyridylhydrazone) and their coordination with zinc(II) and iron(II) metal ions in different experimental conditions. Herein, we provide a detailed description of the synthesis and structural characterization of a series of zinc(II) and iron(II) complexes with the butane-2,3-dione bis (2 ′ -pyridylhydrazone) ligand that is either in the neutral or (bis)deprotonated form. The characterization of complexes (1-6) has been carried out on the basis of their analytic and spectroscopic parameters (see the experimental section).
Crystallographic data were collected at 183(2) K with either Mo K α radiation (λ = 0.7107 Å) or Cu K α radiation (λ = 1.5418 Å). The complexes (2)(3)(4)(5)(6) were measured on an Rigaku Su-perNova, Dual source (Rigaku Europe SE, Neu-Isenburg, Germany), with an Atlas detector, while complex 1 was measured on an Rigaku Oxford Diffraction CCD Xcalibur system with a Ruby detector (Rigaku Europe SE, Neu-Isenburg, Germany). Suitable crystals were covered with oil (Infineum V8512, formerly known as Paratone N; Infineum, Milton Hill, UK), placed on a nylon loop that was mounted in a CrystalCap Magnetic™ (Hampton Research, Aliso Viejo, CA, USA), and immediately transferred to the diffractometer. Data were corrected for Lorentz and polarization effects as well as for absorption (numerical). The program suite CrysAlis Pro was used for data collection, multi-scan absorption correction, and data reduction [45]. Structures were solved with direct methods using SIR97 [46] and were refined by full-matrix least-squares methods on F 2 with SHELXL-2018 [47]. The structures were checked for higher symmetry with the help of the program Platon [48]. The graphical output was produced with the help of the program Mercury [49]. Further crystallographic information can be found in the Supplementary Materials (Table S1). CCDC entries 1017003-1017008 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html (accessed on 16 August 2021).

Synthesis of Neutral Zinc(II) Complexes
General Procedure [Zn(LH 2 )Cl 2 ] (1): A hot methanolic (20 mL) solution of LH 2 (185 mg, 0.689 mmol) was added to a hot methanolic solution of zinc(II) chloride (110 mg, 0.807 mmol) in a 50-mL round bottom flask under nitrogen atmosphere. The above reaction mixture was allowed to reflux for 2 h, and the reaction progress was monitored through thin layer chromatography. During the reaction, an orange-red solid was precipitated. The solid that formed was filtered off, washed with cold methanol, and dried in vacuo. Single crystals suitable for Xray diffraction analysis were grown from a mixture of an acetonitrile-water solution at room temperature. Yield (0.253 g, 90%), elemental analysis calcd (%) for C 14   [Zn(LH 2 )(N 3 ) 2 ] (3): A 15-mL methanol solution of complex 1 (50 mg, 0.0124 mmol) and NaN 3 (16 mg, 0.0246 mmol) was mixed in 10 mL of water and stirred at room temperature overnight. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mass was filtered, and the corresponding filtrate was slowly evaporated at room temperature. The greenish yellow crystals of [Zn(L)(N 3 ) 2 ] (3) were isolated (43 mg, 83% yield). Complex 3 was also prepared by the reaction of ligand (LH 2 ) with ZnCl 2 /NaN 3 (1:2 ratio), which were mixed with 15 mL of methanol and 5 mL of water and heated to reflux for 6 hours. The greenish yellow crystals of complex 3 were isolated with 73% yield. Elemental analysis calcd (%) for C 14  [Zn(LH 2 )(OTf) 2 ] (4): 100 mg of LH 2 and 135 mg of Zn(OTf) 2 were dissolved in 10 mL of acetonitrile. After 24 h, the precipitated solid was isolated by filtration and drying. Yield (0.168 g, 71%), elemental analysis calcd (%) for C 16
[Fe(LH) 2 ]·H 2 O (6): Ligand (LH 2 ) (0.025 g, 0.0925 mmol) and iron(II) bis (trimethylsilyl) amide (0.035 g, 0.0929 mmol) were dissolved in 4 mL of dry acetonitrile. The reaction changed their color into a brownish red, and the reaction was stirred for 24 h at RT. The reaction mixture was filtered, and the resulting brownish red suspension was washed with pentane (10 mL). Single crystals of 6 were obtained by slow evaporation of the solvent from a saturated solution in dry acetonitrile, yield 11 mg (19%, based on iron salt

Synthesis and Characterization
The neutral N4-tetradentate ligand LH 2 was prepared according to a procedure described in the literature [41,42] by employing the condensation reaction of two equivalents of 2-hydrazinopyridine and one equivalent of 2,3-butanedione. The prepared ligand LH 2 was characterized by NMR and ESI-MS. The subsequent reactions between LH 2 and the metal salts are shown in Scheme 2. Complexes 1, 2, and 4 were synthesized from an equal molar ratio of ligand LH 2 and ZnX 2 (X = Cl, OAc, and OTf) in the presence of methanol as a solvent. Complex 3 was synthesized either from complex 1 or as complex 1 but in the presence of an additional two equivalents of sodium azide. In all of the reactions, coordination was immediate and followed by formation of a solid. The solid residue thus obtained was filtered and washed with cold methanol and diethyl ether. The yields of the complexes were relatively good, and the details are given in the experimental section. All the new complexes (1-4) were isolated as colorless to yellow, air stable solids, and are non-hygroscopic in nature. The synthesized complexes are highly soluble in water and DMSO, and partially soluble in chloroform. On the other hand, the Zn(II) complex 5 and the mono nuclear Fe(II) complex 6, both with a deprotonated ligand, were synthesized in the glove box by treating an equal molar ratio of ligand and the corresponding silyl amide salts in either THF or acetonitrile as solvent (Scheme 2). The complexation processes were monitored by 1 H NMR spectroscopy. After the completion of the reaction, the solvent was evaporated, and the residue was washed with dry pentane.
The Zn-Zn dimer and iron(II) complexes are pink and brown colored solids, respectively, that are insoluble in apolar solvents but are highly soluble in chloroform and acetonitrile, respectively. The synthesized complexes 1-6 were characterized by X-ray and ESI-MS. Structural studies of complexes 1-4 showed that the ligand acts as a planar tetradentate chelate ligand coordinating through the imine and the pyridine nitrogen atoms, while in complex 5, one bisdeprotonated ligand coordinates to two different zinc metal centers, and in complex 6, each monodeprotonated ligand only coordinates with three nitrogen atoms to the iron.

NMR Spectra of the Zinc Complexes 1-4
Zinc complexes 1-4 were fully characterized, and their structures in solution were investigated in detail via NMR spectroscopy with the aim of understanding the coordination environment around the metal center. Zinc would be expected to elicit slight 1 H shift differences relative to the frequencies of the free ligands. The 1 H-NMR spectrum of the symmetrical complex 1 in D 2 O shows five well-resolved signals: (i) four aromatic signals in the low-field region (between 6.5 and 8.2 ppm, detailed assignment in the experimental section); (ii) a sharp singlet around 2.30 ppm corresponding to the methyl protons of the ligand, which is slightly downfield shifted relative to the free ligand (2.22 ppm). Similar spectral patterns were also observed for the other neutral complexes 2-4 (see also the Supplementary Materials ( Figures S1 and S2)). In the case of the zinc acetate complex 2, an additional sharp singlet was observed to occur at 1.90 ppm.

Description of Crystal Structures
As part of the structural characterization, the molecular structures of complexes 1-6 were determined by single crystal x-ray analysis. Transparent crystals of complexes 1-4 suitable for X-ray diffraction analyses were obtained by the slow vapor diffusion of hexane into the saturated acetonitrile/dichloromethane solutions at ambient temperature [50]. On the contrary, crystals of the Zn-Zn dimer (5) and the iron(II) complex (6) were grown by slow evaporation of THF and acetonitrile, respectively, in the glove box. The ellipsoidal representations with atom numbering are shown in Figures 1-6, and selected bond lengths and angles are given in the corresponding figure captions. Crystal data and data collection details of complexes 1-6 are presented in Table S1. Zn(LH 2 )Cl 2 (1) crystallized in the monoclinic space group P2/n. The molecular structure of complex 1 adopts an octahedral geometry, with the metal center being coordinated by the chelating N4 ligand (two pyridine and two imine nitrogen atoms) in the equatorial plane and by two axial chloride atoms. The two-fold axis of the space group bisects the C9-C9# bond. The equatorial coordination of the N4 ligand to the zinc center forces the two chloride ligands to be placed trans to each other with a bond angle of Cl(1)-Zn(1)-Cl(1)#1 that is 168.81 (3) • . This is one of the few trans bond angles that is off 180 • for ZnN 4 Cl 2 complexes [51][52][53] (see the following references with examples of 180 • Cl-Zn-Cl bond angles: [54,55]). Notably, 29 out of 40 of the ZnN 4 Cl 2 complexes in the CSD database [56] actually have a cis arrangement of the chlorides (see [57,58]). All of the bond distances and bond angles in the crystal structure are comparable with similar distances in other structurally characterized six-coordinate zinc(II) complex-containing terminal chlorides [59,60].     respectively. This bent-on coordination of inorganic azides to metal centers has been very nicely explained by Dori et al. [61]. There has been only one previously reported ZnN 4 (N 3 ) 2 complex with the two azides in trans position that have an N(azide)-Zn-N(azide) angle off 180 • [62]. Again, all of the other reported ZnN 4 (N 3 ) 2 complexes with the two azides in trans position have a N(azide)-Zn-N(azide) angle of exactly 180 • (see, for example, [63]).
Furthermore, the pink-red and dark brown-colored crystals corresponding to 5 and 6 were isolated by the reaction of the ligand with [Zn{N(SiMe 3 ) 2 } 2 ] and [Fe{N(SiMe 3 ) 2 } 2 ], respectively, in the presence of dry THF solvent. The crystals (5, 6) that were formed are thermally stable and can be crystallized after workup from pentane and evaporation at room temperature. Complex 5 crystallizes in the monoclinic space group I2/a ( Figure 5), and the representation of the asymmetric unit of complex 5 is given in the Supplementary Materials ( Figure S3). Examination of the solid-state structure reveals it to be a neutral complex in which each zinc atom in this molecule is four-fold coordinated and is surrounded by two imine and two pyridine nitrogen donors. The double deprotonation from either side of NH generates the dearomatized Zn-Zn dimer, and the dearomatized structure is clearly indicated by the considerably shorter C2−N7 bond (1.339 (5) Figure 7). The distance between the Zn· · · Zn centers (3.0857(10) Å) is a very comparable range to that found in other dimeric zinc(II) complexes with tetrahedral arrangements [64,65]. In the iron(II) crystal structure, the ligand underwent NH deprotonation on one side followed by the iron coordination with three nitrogen atoms (two imine nitrogen and one pyridine nitrogen atom). The coordination sphere of the iron center is completed with a second equally monodeprotonated ligand (Figure 7).

Conclusions
In conclusion, we have reported a new series of neutral, mono, and doubly deprotonated zinc(II) and iron(II) complexes containing N4 ligand LH n (n: 0-2). The synthesized complexes (1-6) have been carefully studied by extensive spectroscopic and structural characterization. Single crystal X-ray diffraction method revealed that an N4 neutral ligand was coordinated to iron(II) and zinc(II) via two imine nitrogen atoms and pyridine nitrogen and demonstrated the presence of a typical four-and six-coordinate geometry around the metal center. Interestingly, complex 5 represents an unusual four coordination of two zinc centers along with two molecules of doubly deprotonated ligand. On the other hand, complex 6 shows a distorted octahedral geometry around iron(II) with two molecules of mono-deprotonated ligand.