Dioxidomolybdenum(VI) complexes with isoniazid-related hydrazones: solution-based, mechanochemical and UV-light assisted deprotonation

Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. Accepted Manuscript NJC


Introduction
The chemistry of hydrazones is continuing to be an interesting area of research because of their modularity, easiness of synthesis and stability towards hydrolysis. 1 It is known that aroylhydrazones can exist in solution as configurational isomers (in E or Z forms) or in tautomeric forms (QN-NH-(CQO)-or QN-NQ(C-OH)-) that occur in equilibrium.In most cases they have an acidic proton and their coordination to transition metals often leads to proton displacement. 1Depending on the protonaccepting ability, metal complexes with neutral (H 2 L), singly-(HL À ) and doubly-deprotonated ligands (L 2À ) can be obtained. 2n such a way different dimensionalities of the hydrogen-bonded networks can be formed.The protonation state of these ligands in metal complexes plays an important role since it offers finetuning of properties such as electrochemical, photophysical or catalytic. 3Recent attention has been paid to the configurational switching mechanism based on coordination-coupled deprotonation which explains the role of hydrazone deprotonation in activating the molecular switch. 4soniazid-related aroylhydrazones and their coordination compounds are of great interest owing to their biological activities 5 and their structural diversity.7][8][9] Otherwise, the sixth coordination site is occupied by the oxygen atom from the solvent D thus forming mononuclear complexes [MoO 2 (L)D].In these compounds, the hydrazone ligand is in the doublydeprotonated (L 2À ) form.Surprisingly, chloride salts of charged dioxidomolybdenum(VI) complexes with tridentate ONO-donor ligands are very rare.Only two such structures have been published to date. 10 A typical method employed in the preparation of some fully deprotonated metal complexes involves addition of a base during the complexation reaction, commonly in organic solvents. 1o the best of our knowledge, alternative methods towards deprotonation of cis-dioxidomolybdenum(VI) complexes (including grinding or UV irradiation as the method of activation) were not investigated.With these possibilities in mind, we set out to explore the influence of UV light on singly protonated isonicotinoyl hydrazone complexes to see if deprotonation of the pyN-H + moiety could proceed without a photoinduced E-to-Z configurational switch about the hydrazone double bond.Deprotonation has been investigated also by using Et 3 N as a base (by a conventional solution-based method and a mechanochemical approach).To achieve this aim we have prepared and characterized dioxidomolybdenum(VI) complexes [MoO 2 (HL R )(MeOH)]Cl (1-3) with three ligands, H 2 L R , salicylaldehyde isonicotinoylhydrazone (H 2 L SIH ), 2-hydroxy-naphthaldehyde isonicotinoylhydrazone (H 2 L NIH ), and p-(N,N 0 -diethylamino)salicylaldehyde isonicotinoylhydrazone (H 2 L Et2NSIH ), Scheme 1.We were also interested to investigate the importance of nonbonding interactions in the structures as well as the ability of these complexes to form different hydrogen-bonded networks depending on the protonation state of the complexes.

Synthesis of dioxidomolybdenum(VI) complexes
Synthesis of [MoO 2 (HL R )(MeOH)]Cl was carried out in dry methanol using MoO 2 Cl 2 and the corresponding aroylhydrazone H 2 L R (R = SIH, NIH or Et 2 NSIH), Scheme 2. In all of the investigated compounds formed after chelation, the ligands are found to be in the singly-deprotonated form (HL R ) À coordinated to the cis-{MoO 2 } 2+ core via the ONO donor atoms.The cis-{MoO 2 } 2+ core is additionally coordinated by a solvent molecule resulting in the formation of [MoO 2 (HL R ) (MeOH)]Cl, where R = SIH (1), NIH (2) or Et 2 NSIH (3), respectively.If the reaction was not performed in dry methanol a mixture of the corresponding [MoO 2 (HL R )(MeOH)]Cl and [MoO 2 (HL R )(H 2 O)]Cl complexes was obtained.All of the isolated compounds 1-3 are moisturesensitive crystalline solids (Fig. S1, see ESI †).Exposure of samples 1-3 to water vapour resulted in crystalline products distinct from the starting compounds.In all cases they were identified to be [MoO 2 (HL R )(H 2 O)]Cl (1a-3a) where the coordination sphere around the molybdenum atom is completed by coordination of a water molecule.Crystals of 1a suitable for single crystal X-ray diffraction were obtained from wet methanol, whereas those of 2a and 3aÁH 2 O were obtained from wet acetonitrile.This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015 isolation of the corresponding mononuclear complex.It is expected that the deprotonation reaction leads to the formation of a labile intermediate complex with the coordinated methanol molecule, which is then displaced by the isonicotinoyl part of the neighbouring molecule.Compounds 4-6 were synthesised more easily by liquid-assisted grinding (LAG) of the complexes 1-3 and Et 3 N in the presence of a small amount of methanol (method B).Triethylammonium chloride impurities can be removed by rinsing the products with water affording 4-6 in a pure, chloride-free form.Compounds 4-6 can be prepared alternatively by photoassisted deprotonation of the corresponding complexes 1-3 (method C).To achieve deprotonation, mononuclear complexes were exposed to UV radiation (254 nm) in dry methanol.Absence of chloride in the prepared compounds was proven by a negative test reaction with aqueous AgNO 3 .

Deprotonation reactions
In complexes 4-6, the ligands are coordinated tridentately in the doubly-deprotonated form (L R ) 2À to the molybdenum centre.The remaining sixth coordination site is occupied by the oxygen atom of the solvent methanol molecule (in 4 and 5) or by the nitrogen atom of the bridging isonicotinyl moiety of the neighboring complex (in 6).This suggests that the obtained complexes are inert towards further photoisomerization.To the best of our knowledge, deprotonation of cis-dioxidomolybdenum(VI) complexes leading to formation of the mononuclear complexes or polynuclear assemblies through a UV-light assisted reaction or by mechanochemical synthesis has not been reported so far.
Crystal and molecular structures of 5 and 6 were determined by the single crystal X-ray diffraction method.The crystals of 4 are identical to those known from the literature. 11The products obtained by methods A, B and C (Scheme 2) were examined also by PXRD, Fig. 1 (Fig. S2 and S3, see ESI †).Although grinding of 1-5 during sample preparation for PXRD experiments resulted in a partial release of the coordinated solvent molecule (about 1% according to TG measurements) this change was not significant and PXRD patterns could be used for comparison with those calculated from the structures obtained by the single crystal X-ray diffraction method.

Thermogravimetric analyses
Crystals of all samples were used for TG analysis without grinding in the atmosphere of pure oxygen (at a heating rate of 5 1C min À1 ).TG study of the [MoO 2 (HL R )(MeOH)]Cl complexes revealed that three main processes occurred: desolvation, loss of a HCl molecule and decomposition.In the case of the mononuclear complexes 1 and 2 the loss of MeOH

Spectroscopic characterisation
All complexes were characterized also by IR spectral data.Compounds were identified by the appearance of the stretching frequencies characteristic for n asym (MoO 2 ) (found at about 945-935 cm À1 ) and antisymmetric combination of MoQO and Mo-O EtOH stretchings (found at ca. 910 cm À1 for 1-5).The corresponding symmetric stretching bands n sym (MoO 2 ) having significantly lower intensities appear in the same region but they either overlap with the asymmetric ones or appear as shoulders. 12The bands found in the IR spectra of H 2 L R , characteristic for the CQO vibration at ca. 1680 cm À1 and N-H vibration (at 3180 cm À1 (H 2 L SIH ), 3223 cm À1 (H 2 L NIH ), 3215 cm À1 (H 2 L Et2NSIH )), are absent in the IR spectra of 1-3, suggesting the hydrazone tautomerism (QN-NH-(CQO)--QN-NQ(C-OH)-), deprotonation and coordination through the oxygen atom.This is also supported by the presence of a new band at ca. 1330 cm À1 assigned to the C-O group of the hydrazone moiety. 13The bands typical for CQN imine and C-O phenolic appear at ca. 1610 cm À1 and 1550 cm À1 , respectively.A band at around 1050 cm À1 seen in the IR spectra of 1-5 is assigned to the C-O stretching vibration of the coordinated MeOH molecule. 14This band is absent in the spectra of 1a-3a and 6.Formation of the Mo-N isonicotinyl bond is additionally supported by the presence of a band at 907 cm À1 assigned to n asym (OQMo-N isonicotinyl ) and absence of a broad band at E850 cm À1 characteristic for an intermolecular MoQOÁ Á ÁMo interaction. 15he NMR analysis has confirmed chemical structures of all compounds in solution.The proton and carbon chemical shifts (Tables S1-S3, see ESI †) were assigned by using one ( 1 H and APT) and two-dimensional NMR experiments (COSY, HSQC and HMBC).The proton spectra of the ligand molecules displayed signals resonating at B11 ppm and B12 ppm which were assigned to OH and NQNH protons, respectively (Fig. 2).The signals were somewhat broadened indicating their involvement in hydrogen bonding interactions.
In the compounds [MoO 2 (HL R )(MeOH)]Cl (1-3) these signals disappeared indicating their deprotonation upon coordination of the ligand to molybdenum.Simultaneously, the pyridine nitrogen became protonated which is supported by the appearance of new signals at 3.17   This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015 down-field shifts observed for neighboring hydrogen and carbon atoms (as can be noticed in Fig. 2), as a result of electron redistribution upon complexation.The largest effects were detected in compound 6 for carbons C-5 and C-7,9 amounting to 5.42 ppm and À5.15 ppm, respectively.The atoms C-6,10, C-4 and C-1 were also affected but to a smaller extent.These findings are in accordance with the crystal structures obtained for these compounds.

Crystallographic studies
The ligand coordinates the metal centre of the cis-MoO 2 2+ core tridentately via the phenolic-oxygen, azomethine-nitrogen and isonicotinic-oxygen forming five and six membered chelate rings in all complexes.The sixth coordination molybdenum site is occupied by the oxygen atom from the solvent (methanol or water) thus forming mononuclear complexes 1-3 (Fig. 3), 1a, 2a, 3aÁH 2 O (Fig. 4) and 5 (Fig. 5(a)).An exception is the coordination polymer 6 (Fig. 5(b)) where the coordination sphere is completed by the nitrogen atom of the isonicotinyl moiety of a neighboring molybdenum complex.This moiety acts as a linker between the molybdenum centers and enables formation of a larger structural assembly, a 1D zig-zag coordination polymer.In all reported complexes the coordination sphere of molybdenum is a distorted octahedron (Tables 1 and 2).The smallest cis-angle at the Mo atom is that of O1-Mo-N1 being in the range from 71.63(5)1 in 1 to 72.42 (8)1 in 2a, while the largest one involves the oxo-oxygen atoms O3-Mo-O4 being in the range from 105.21 (7)1 in 1 to 105.99(9)1 in 5.
The distance from the molybdenum atom to the O atom from the solvent molecule (1-3, 5, 1a, 2a, 3aÁH 2 O) or the N atom of the isonicotinyl moiety (6) represents the largest bond length within the octahedron.The ligand is singly deprotonated in compounds 1-3 and 1a, 2a and 3aÁH 2 O which are all chloride salts, whereas in compounds 5 and 6 it is doubly deprotonated resulting in neutral complexes.The ligands are not planar, the smallest and largest deviation from planarity is that between the isonicotinyl and phenyl/naphthaldehyde moieties in compounds 6 (3.85(12)1) and 2, respectively (8.47(9)1, Table S4, see ESI †), and between the five-and six-membered chelate rings in compounds 3 (5.20(10)1)and 5 (8.32(9)1,Table S4, ESI †).The C1-N1 bond in the complexes is not significantly different from that in the free ligands. 16,17However, the bond length N2ÀC2 is shortened, whereas that of N1ÀN2 is lengthened in the complexes in comparison to the free ligands H 2 L NIH (1.357(3) Å and 1.370(2) Å, respectively) 16 and H 2 L SIH (1.3558(17) Å and 1.3699(15) Å, respectively) 17 due to the electron delocalization.
Complexes 1, 2 and 3 (Fig. 6) have two hydrogen bond donors, the methanol hydroxyl group and the protonated nitrogen atom of the isonicotinyl moiety.They are both involved in hydrogen bonding to the chloride ion (Table S5, see ESI †).Hydrogen bonds of the type NÀHÁ Á ÁCl are in the range from 2.988(3) Å in 3 to 3.0199(16) Å in 1, and are shorter than those involving the hydroxyl group, OÀHÁ Á ÁCl which are from 3.057(3) Å in 3 to 3.0936( 16) Å in 1.
The longer hydrogen bonds are formed in 1 and 2 where the hydrogen bonds connect the complex molecules into infinite one-dimensional chains (C 1 2 (11)) parallel to the c-axis, in contrast  to 3 which is built up of centrosymmetrical dimers (R 2 4 ( 22)).Therefore, in these three complexes the typical hydrogen bonding connection is NÀHÁ Á ÁClÁ Á ÁHÀO, which is either bent (1 and 3) or linear (2).It seems that the linear connection is more favorable for a shorter distance between the p systems (Fig. 6).
Complexes 1a, 2a and 3aÁH 2 O (Fig. 7) have a water molecule coordinating the molybdenum atom and so there is one more hydrogen atom donor than in 1-3 thus forming a more extensive hydrogen bonding network.Indeed, both hydrogen atoms are involved as donors, in 1a and 2a toward chloride ions, while in 3aÁH 2 O one is toward a chloride ion and the other toward the solvent water molecule.The presence of the solvent water molecules increases the number of hydrogen bonds that are found in the structure 3aÁH 2 O.The chloride ion is an acceptor of three (1a and 3aÁH 2 O) or four (2a) hydrogen bonds.
Interestingly, only two ionic chloride structures of molybdenum complexes with ONO-donor ligands were found in the Cambridge Structural Database: 18 cis-dioxido-methanol-(N-salicylidene-N 0 -(pyridinium)ethylidenehydrazone)-molybdenum(VI) chloride, 10b and  Complexes 5 and 6 are deprotonated and chloride free 2 and 3, respectively.In 5 the molecules are connected by hydrogen bonds into helical chains around the 4 1 axis involving the methanol hydroxyl group and the deprotonated isonicotinyl nitrogen OÀHÁ Á ÁN of 2.709(3) Å.The chains are connected by pÁ Á Áp interactions between the isonicotinyl and naphthaldehyde moieties with the strongest interactions between centroids Cg3Á Á ÁCg5[1 À x, Ày, Àz] of 3.7563(15) Å suggesting that pÁ Á Áp interactions are weaker than in 2 (Fig. 8a and Table S6, ESI †).The only complex with no classical hydrogen bonds within this study is 6.The polymeric zig-zag chains are parallel to the b-axis (Fig. 8(b)).There are only van der Waals interactions between the chains.Coordination polymers with such linking through the nitrogen atom are very rare.A methanol solvate of 6 has been recently reported. 9It is also polymeric without hydrogen bonds between the solvent methanol molecules and the complex molecules.Interestingly, the two diethyl substituents are in a trans position whereas in all our structures they are cis to each other.Two other coordination polymers with the linker being the isonicotinyl moiety have been described previously. 6,7Packing diagrams of all complexes are given in Fig. S4 to S11, see ESI. †

Conclusions
Substitution of the chloride ligands in MoO 2 Cl 2 by the corresponding aroylhydrazone ligand H 2 L R in methanol gives rise to formation of the mononuclear complexes [MO 2 (HL R )(MeOH)]Cl (1-3).In these compounds, the ligands (HL R ) À are coordinated to the cis-{MoO 2 } 2+ core via the ONO donor atoms.We have shown that mononuclear complexes 1-3 can be readily deprotonated into the mononuclear [MoO 2 (HL R )(MeOH)] (4 and 5) and/or polynuclear [MoO 2 (L R )] n (6) complexes by using Et 3 N as a base, either by a conventional solution-based method or by a mechanochemical approach.Compounds 4-6 can be prepared alternatively without using a base by photoassisted deprotonation of the corresponding complexes 1-3.The introduction of UV light enables deprotonation without altering the tridentate presentation of donor atoms characteristic of this class of chelating agent.In the polynuclear complex 6, the isoniazid ligand is coordinated instead of the solvent molecule.
A diversity of supramolecular achitectures are formed in the complexes by non-bonding interactions, especially hydrogen bonds and pÁ Á Áp interactions.In the singly-deprotonated ionic complexes 1-3 and 1a-3aÁH 2 O the protonated nitrogen atom of the isonicotinyl moiety and the coordinated solvent molecules  are the hydrogen bond donors while the chloride ion is the main hydrogen bond acceptor (of two hydrogen bonds in 1-3, three in 1a and 3aÁH 2 O, and four in 2a).pÁ Á Áp interactions are found in all of these complexes except 1a and 3aÁH 2 O.The main motifs formed are either layers (1) or chains (2, 3), whereas in 1a, 2a and 3aÁH 2 O which has an extra hydrogen bond donor (coordinated water instead of methanol) there are either layers (1a and 3aÁH 2 O) or a 3D-network (2a).Quite different is the doubly-deprotonated molecular complex 5 where the molecules are connected by hydrogen bonds into helical chains around the 4 1 axis involving the methanol hydroxyl group and the deprotonated isonicotinyl nitrogen.Weak pÁ Á Áp interactions interconnect the chains into a 3D-network.As expected, the complexes with coordinated solvent molecules have low thermal stability.In the structure of the heteronuclear complex 6 there are only van der Waals interactions between the chains.This is also the thermally most stable complex since it is polymeric without coordinated solvent molecules.

Experimental section
Preparative part.Ligands H 2 L SIH , H 2 L NIH , and H 2 L Et2NSIH were prepared by the reaction of isonicotinyl hydrazine (''isoniazid'') with an appropriate aldehyde according to the procedures described in the literature. 16The starting MoO 2 Cl 2 was prepared as described in the literature. 19Methanol was dried using magnesium turnings and iodine and then distilled.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015

Fig. 1
Fig. 1 PXRD patterns of 3 (a and b); 6 (c-f).The colored lines indicate patterns obtained by powder diffraction, Cu Ka radiation ((c) sample obtained by method A, (d) sample obtained by method B and (e) sample obtained by method C)), while the black lines indicate patterns calculated from the X-ray single-crystal structures of the corresponding compounds.

Fig. 4
Fig. 4 ORTEP drawings of the ions in 1a (a), 2a (b) and 3aÁH 2 O (c) with the atom-labeling scheme (displacement ellipsoids of non-hydrogen atoms are drawn at the 50% probability level).

Fig. 5
Fig. 5 ORTEP drawings of the molecules of 5 (a) and 6 (b) with the atomlabeling scheme (displacement ellipsoids of non-hydrogen atoms are drawn at the 50% probability level).

Fig. 6
Fig. 6 Nonbonding interactions connecting the ions into supramolecular motifs in 1 (a), 2 (b) and 3 (c).Hydrogen bonds are shown by blue dotted lines.The distance between centroids (green dashed lines) is in Å.

Fig. 7
Fig. 7 Nonbonding interactions connecting the ions into supramolecular motifs in 1a (a), 2a (b) and 3aÁH 2 O (c).Hydrogen bonds are shown by blue dotted lines.The distance between centroids (green dashed lines) is in Å.

Fig. 8
Fig. 8 (a) Nonbonding interactions connecting the molecules into a 3D-network in 5. Hydrogen bonds are shown by blue dotted lines.The distance between centroids is in Å; (b) two polymeric chains in 6.