Structural features, thermal behavior and biological activities of two new organically templated (CoII, NiII) sulfates

Accepted Manuscript Structural features, thermal behavior and biological activities of two new organically II II templated (Co , Ni ) sulfates Salem Saïd, Rihab Ben Abdallah Kolsi, Houcine Naïli PII:

S0022-328X(16)30055-9

DOI:

10.1016/j.jorganchem.2016.02.022

Reference:

JOM 19406

To appear in:

Journal of Organometallic Chemistry

Received Date: 7 January 2016 Revised Date:

12 February 2016

Accepted Date: 18 February 2016

Please cite this article as: S. Saïd, R. Ben Abdallah Kolsi, H. Naïli, Structural features, thermal behavior II II and biological activities of two new organically templated (Co , Ni ) sulfates, Journal of Organometallic Chemistry (2016), doi: 10.1016/j.jorganchem.2016.02.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Structural features, thermal behavior and biological activities of

RI PT

two new organically templated (CoII, NiII) sulfates

a

SC

Salem Saïd a, Rihab Ben Abdallah Kolsi b, Houcine Naïli a *

Laboratoire Physico-chimie de l’Etat Solide, Département de Chimie, Faculté des Sciences

Laboratory of Plant Biotechnology, Faculty of Sciences of Sfax, 3000 Sfax, Tunisia.

AC C

EP

TE D

b

M AN U

de Sfax, B.P. 1171, 3000 Sfax, Université de Sfax, Tunisie.

*Corresponding author Tel: +216 98 660 026; Fax: +216 74 274 437. E-mail address: [email protected]

1

ACCEPTED MANUSCRIPT

Abstract The present paper undertakes the study of two new compounds with similar general formula (C6H9N2)2[MII(H2O)6](SO4)2·2H2O with MII = Ni (1) and Co (2). In this context 1 and 2 are

RI PT

synthesized and characterized by single-crystal X-ray diffraction which revealed that these phases are centrosymmetric and crystallize, respectively, in triclinic and monoclinic symmetries. The thermal properties of both complexes are investigated as well as the IR

SC

spectroscopic and in vitro biological activities. The changes in geometry between these two complexes and intermolecular interactions such as hydrogen bonding and π···π stacking

M AN U

arrangement are discussed. Then, the cohesion between the amine cations, the inorganic parts and the free water molecules is performed via several types of hydrogen bonding forming interesting structural patterns. The pyridinium cations are aligned with each other in a face-toface manner. The interlayer space is filled with aromatic amines that form chains through

TE D

π···π interactions. The interlayer distances are 13.213 and 12.615 Å for 1 and 2, respectively. These materials were evaluated for their in vitro antibacterial activity against Escherichia coli, Salmonella enterica, Bacillus subtilis, Pseudomonas aerigunosa, Staphylococus aureus and

EP

Micrococcus luteus. The ligand and its metal complexes have been also screened for their antifungal activity, using agar disc diffusion, against Aspergilus niger, saccharomyces

AC C

cerevisiae and Candida albicans. In addition, the antioxidant activities of the complexes were also investigated through scavenging effect on DPPH radicals, total antioxidant activity and reducing power.

KEYWORDS:

Crystal

packing,

Intermolecular

interactions,

lamellar

structure,

supramolecular assembly, Biological Activities.

2

ACCEPTED MANUSCRIPT

1. Introduction The design and synthesis of hybrid complexes have attracted great attention in the fields of inorganic and coordination chemistry [1]. Therefore, it extends the range of designing new solids with desired physical and chemical properties [2]. Such as, the supramolecular

RI PT

compounds which exhibit a wide range of technological and industrial applications [3−6]. The main idea in development of the hybrid materials is to take advantage of the best properties of each component that forms an hybrid, trying to decrease or eliminate their drawbacks getting

SC

in an ideal way a synergic effect; that results in the development of new materials with new properties. The bonding in these materials is just as diverse as their structures, with covalent,

M AN U

ionic, and coordination bonds, hydrogen bonding, van-der Waals (vdW) forces, and π···π stacking being observed in a single compound. Furthermore, hydrogen bonding between the organic cations and the metal layers is an important issue in understanding the hybrid organicinorganic materials, which influences both the alignment and spacing of the nearest-neighbor

TE D

metal sheets or chains. Unfortunately, despite some recent progress, the ability to predict and control the supramolecular assembly of molecules remains an elusive goal, and much more work is required to understand the intermolecular forces that determine the patterns of

EP

molecular packing in the solid state. Metal complexes may constitute one such possible class

AC C

exhibiting biological activities [7-10]. Therefore, we have already drawn attention [11] to the strong relationship between metals or their complexes, and antibacterial [12], antitumour [13], and anticancer [14] activities. To the best of our knowledge, complexes in this report have never been explored for their antibacterial, antifungal and antioxidant activities. Therefore, this study opened the doors to develop such supramolecular materials that could be used to treat the diabetes, the anti-cancer and the anti-alzheimer. In the field of our investigations in the organic-inorganic hybrid materials, we report, herein, the chemical preparation, the spectroscopic characterization, the thermal behavior, the

3

ACCEPTED MANUSCRIPT biological activities and the crystallographic description of two hybrid frameworks metal sulfates templated by 2-amino-6-methylpyridinium.

2. Materials and Methods 2.1. Materials

RI PT

In order to obtain crystals of high quality, purification of starting materials was found to be an important step and hence the re-crystallized salts were used for the growth of crystals of studied materials. All chemicals and solvents were purchased from Sigma-Aldrich and it was

SC

further purified by repeated re-crystallization process for three times using de-ionized water as the solvent.

M AN U

2.2. Synthesis

Synthesis of compound 1, (C6H9N2)2[Ni(H2O)6](SO4)2·2H2O: one mmol of Nickel(II) sulfate hexahydrate, NiSO4·6H2O, and two mmol of 2-amino-6-methylpyridine, C6H8N2, were each dissolved in 10 mL of distilled water. The Ni(II) salt solution was then added slowly to the

TE D

ligand solution. The pH of the resulting solution was adjusted between 2 and 3 by dropwise addition of concentrated sulfuric acid H2SO4 until the solution becomes clear. This later left for slow evaporation at ambient conditions. After a few days, green block crystals were

EP

harvested and characterized through single crystal X-ray diffraction.

AC C

Synthesis of compound 2, (C6H9N2)2[Co(H2O)6](SO4)2·2H2O: one mmol of Cobalt(II) sulfate heptahydrate, CoSO4·7H2O, and four mmol of 2-amino-6-methylpyridine, C6H8N2, were each dissolved in 10 mL of distilled water. The resulting solution was then added to an aqueous solution of sulfuric acid (initial and final pH: 2, 3) and stirred for 30 min. After agitation, the solution was left to slowly evaporate at room temperature. Pink block crystals suitable for Xray structure analysis formulate and remain stable under normal conditions of temperature and humidity.

4

ACCEPTED MANUSCRIPT 2.3. Single-Crystal X-ray Diffraction Details of crystallographic data collection and refinement parameters for complexes 1 and 2 are given in Table 1. Single crystals of dimensions 0.37×0.31×0.24 (1) and 0.50×0.45×0.35 (2) mm, were mounted onto glass fiber and cooled to low temperatures. Data were performed,

RI PT

respectively, on a Kuma KM-4-CCD and Xcalibur Ruby diffractometers with graphite monochromatized Mokα radiation (λ = 0.71073 Å), using an Oxford Cryosystems cooler. Data collection, cell refinement, data reduction and analysis were carried out with

SC

CrysAlisPRO [15]. Analytical absorption correction was applied to the data with the use of CrysAlisRED [15]. Structures were solved with direct methods using SHELXS-97 [16] and

M AN U

refined by a full-matrix least squares technique with SHELXL-97 [16] with anisotropic thermal parameters for all non H-atoms. The aqua H atoms were located in a difference map and refined with O–H distance restraints of 0.85(2) Å and H–H restraints of 1.39(2) Å so that the H–O–H angle fitted to the ideal value of a water molecule. Hydrogen atoms bonded to C

TE D

and N atoms were positioned geometrically and allowed to ride on their parent atoms, with C– H = 0.95 Å and N–H = 0.88 Å. All figures were made using DIAMOND program [17]. 2.4. Spectroscopic measurements

EP

Infrared measurements were obtained using a PerkineElmer FT-IR spectrometer. Samples were diluted with spectroscopic grade KBr and pressed into a pellet. Scans were run over the

AC C

range of 4000-400 cm-1.

2.5. Thermal analysis measurements TGA-DTA measurements of complexes 1 and 2 were performed using a 'SETSYS Evolution' (Pt crucibles, Al2O3 as a reference) instrument, under air flow (100 ml/min), for any compound, with a heating rate of 5°C min-1 up to 600°C. 2.6. In vitro biological activities 2.6.1. Determination of in vitro antioxidant activities

5

ACCEPTED MANUSCRIPT 2.6.1.1. DPPH radical scavenging activity The DPPH radical scavenging activity of the samples was evaluated according to the method of Blois [18]. The absorbance was measured spectrophotometrically at 517 nm using model

following formula:

RI PT

JENWAY 6300 spectrophotometer. The percent of inhibition (PI) was calculated using the

Scavenging activity (%) = ((A0 – A1)/A0) x 100

determinations were performed in triplicate. 2.6.1.2. Determination of total antioxidant capacity

SC

Where A0 is the optical density of the blank and A is the optical density of the sample. All

M AN U

Total antioxidant activity of the different concentrations of 1 and 2 was determined according to the method of Prieto et al. [19]. Briefly, 0.3 ml of samples was mixed with 3.0 ml reagent solution (0.6 M sulfuric acid, 28 mM sodium phosphate and 4 mM ammonium molybdate). The Reaction mixture was incubated at 95°C for 90 min in a water bath. After the mixture had

TE D

cooled to room temperature, the absorbance of each solution was measured at 695 nm against a blank. The antioxidant capacity was expressed as ascorbic acid equivalent. 2.6.1.3. Reducing power

EP

Reducing power of the complexes 1 and 2 was determined by the method described by M. Oyaizu [20]. Briefly, 1.0 ml containing five different concentrations of samples was mixed

AC C

with 2.5 ml phosphate buffer (0.2 M, pH 6.6) and 2.5 ml potassium ferricyanide (1%). The reaction mixture was incubated at 50°C for 20 min. After incubation, 2.5 ml trichloroacetic acid (10%) was added and centrifuged (650 × g) for10 min. From the upper layer, 2.5 ml solution was mixed with 2.5 ml distilled water and 0.5 ml FeCl3 (0.1%). Absorbance of all the sample solutions was measured at 700 nm. The reducing power of ascorbic acid was used as positive control. 2.6.2. Antimicrobial activity

6

ACCEPTED MANUSCRIPT 2.6.2.1. Test microorganisms The antibacterial activities of newly synthesized compounds 1 and 2 were tested against 6 strains of bacteria, namely Escherichia coli (ATCC 8739), Salmonella enteria (ATCC 43972), Pseudomonas aerigunosa (ATCC 49189), Staphylococus aureus (ATCC6538),

RI PT

Micrococcus luteus (LB 14110), and Bacillus subtilis (ATCC 6633).

Antifungal activities were tested using Aspergilus niger, saccharomyces cerevisiae and Candida albicans. Those fungal strains were kindly provided by the microbial collection of

SC

the biology department, Faculty of Science, Sfax-Tunisia. 2.6.2.2. In-vitro antibacterial activity

M AN U

The antibacterial activities were evaluated by the agar well diffusion method. All the microbial cultures were adjusted to 0.5 McFarland standards. Mueller Hinton agar medium (20 ml) was poured into each Petri plate and plates were swabbed with 100 µl inocula of the test microorganisms and kept for 15 min for adsorption. Using a sterile cork borer of 6 mm

TE D

diameter, wells were bored into the seeded agar plates and these were loaded with a 100 µl solution of each compound in dimethylsulphoxide (DMSO) with a concentration of 4.0 mg/ml. All the plates were incubated at 37°C for 24 h. Antibacterial activity of each synthetic

EP

compound was evaluated by measuring the zone of growth inhibition against the test organisms with a zone reader (Hi Antibiotic zone scale). DMSO was used as a negative

AC C

control where as Ampicillin was used as a positive control. This procedure was performed in three replicate plates for each organism [21]. 2.6.2.3. In-vitro antifungal activity The antifungal activities of these two metal complexes were evaluated by employing disc agar diffusion method using Sabouraud Dextrose agar (SDA). An aliquot (100 µl) of each compound having a concentration of 4.0 mg/ml was deposited on sterile paper discs (6 mm diameter) which were subsequently placed in the inoculated Petri dishes. DMSO was used as

7

ACCEPTED MANUSCRIPT the negative control where as cycloheximide was used as the positive control. The experiments were performed in triplicates. 2.6.2.4. Minimum inhibitory concentration (MIC) The minimum inhibitory concentration (MIC) of the various compounds was determined by a

RI PT

micro-well dilution method [22]. The inoculum of each bacterium was prepared and the suspensions were adjusted to 106 CFU/ml, and 100 µl of the test compounds were added.

values were done in triplicate.

3. RESULTS AND DISCUSSION

SC

MIC was observed after incubating the inoculated tubes at 30 or 37°C for 24 h. The MIC

M AN U

3.1. Description of the structure of (C6H9N2)2[Ni (H2O)6](SO4)2·2H2O

The molecular structure of (C6H9N2)2[Ni(H2O)6](SO4)2·2H2O (1) was confirmed by a single crystal X-ray analysis. Suitable crystals of this complex belong to the triclinic P space group with two molecules in the unit cell. A complete list of structure factors can be seen in table 1.

TE D

As the X-ray result demonstrated, complex 1 is a mononuclear compound in which the both nickel atoms, lying in special positions on inversion centers, are coordinated by six water molecules from which three are crystallographic independent, while all the other atoms

EP

occupy general positions, two mono-protonated 2-amino-6-methylpyridinium as counterions,

AC C

two sulfate anions and two non-coordinated water molecules (figure 1a). One notable feature in this structure is that each Ni(II) atom has coordination number of six. Hence, the average value of Ni-OW bond distances vary from 2.0414(10) to 2.0698(10) Å and the angles OW-NiOW are in the range 85.95(5)-180°. In comparison with the previous results reported in the literature for similar compounds. These values, are slightly different to those found in the Nicomplexes templated by R-2-methylpiperazine, (Ni-OW = 2.054(2)-2.071(2) Å and OW-NiOW = 85.46(9)-178.33(1)° [23]), and 2-methylpiperazine, (Ni-OW = 2.056(2)-2.065(2) Å and OW-Ni-OW = 85.98(9)-94.02(9)° [24]). The detailed list of bond lengths and angles of 8

ACCEPTED MANUSCRIPT complex 1 was quoted in table 2a. Therefore, as expected, the octahedral geometry around the metal atoms in this compound is slightly distorted. The Ni···Ni distance is 6.968 Å, which is shorter than those found in others analogous phases containing R-2-methylpiperazinediium cations, 7.303 Å [23] and 7.034 Å in nickel sulfates templated by 2-methylpiperazinediium

RI PT

[24]. The uncoordinated water molecules play a significant role to provide the supramolecular aspect of the inorganic layer forming a connecting bridge between the isolated Ni-octahedra and sulfate tetrahedra. Indeed, the oxygen of H2O molecule may be, at the same time, an

SC

hydrogen bond acceptor given from oxygen atom of water molecule coordinated to the metallic octahedron and an hydrogen bond donor toward oxygen of anionic sulfate (fig. 2a).

M AN U

These entities are linked together by O-H···O hydrogen-bonding network, ranging between 2.702 and 3.071 Å (table 3a). The supramolecular crystal structures of 1 is built from the alternatively arranged inorganic and organic layers. The structure is stabilized by O-H···O hydrogen bonding between the different inorganic entities, N-H···O and C-H···O hydrogen

TE D

bonding between the inorganic and organic moieties and π stacking interactions between the aromatic rings of the amine molecules themselves (table 3a). The organic sheets, which are connected by π···π interactions, are intercalated between the inorganic layers. The interlayer

EP

space between two inorganic sheets in this compound is of 13.213 Å which equal to the value

AC C

of the b unit cell parameter (fig. 3a). The aromatic ring of the protonated, 2-amino-6methylpyridinium, cation is planar. Distances and bond angles describing different entities are shown in table 2a. The cations contain a protonated N atoms in the pyridine rings. More specifically, protonation of the nitrogen atom leads to an increase in the C−N−C angle in comparison with the unprotonated pyridine [116.94 (3)°]. Therefore, the observed angles of C−N−C in 1 are 123.44 (11) and 123.85 (11)°. The pyridine rings of neighboring molecules interact with each other via π···π stacking, with a centroid···centroid distances of 3.584(2) and

9

ACCEPTED MANUSCRIPT 3.779(2) Å. The π···π interactions in 1 are of the parallel-displaced configurations [25] see Figure 4a. 3.2. Description of the structure of (C6H9N2)2[Co(H2O)6](SO4)2·2H2O (C6H9N2)2[Co(H2O)6](SO4)2·2H2O (2) crystallizes in the monoclinic symmetry with the

RI PT

centrosymmetric space group P21/c (Z = 8). A complete list of structure factors can be seen in table 1. As the X-ray result confirmed, complex 2 is a mononuclear compound. Therefore, it consist of three cobalt(II) cations octahedrally coordinated by six water molecules, four

SC

isolated sulfate anions, four 2-amino-6-methylpyridinuim cations, one of them is crystallographically disordered [N1D, C2D, C3D, C4D, C5D, C6D, C7D, N2D to N1E, C2E,

M AN U

C3E, C4E, C5E, C6E, C7E, N2E] (fig. 1c), and four uncoordinated water molecules (fig. 1b). The cobalt cations Co2 and Co3 are located in special positions on crystallographic inversion centers and each one is coordinated by six oxygen atoms of which three are crystallographically independent. Whereas, all the other atoms are located in general

TE D

positions. The hexaaquacobalt(II) octahedra are slightly distorted. Indeed, the cobalt–oxygen distances vary from 2.063(2) to 2.118 (2) and the bond angles O(water)-Co-O(water) are in the range 86.02(2) and 180° as quoted in table 2b. The cobalt octahedra are separated from

EP

one to each other with a shortest metal–metal distance of Co–Co = 7.364(2) Å. The inorganic layer in 2 is parallel to the (b, c) plane (figure 2b) and is constructed by the cobalt octahedra,

AC C

sulfate tetrahedra and the free water molecules interconnected and stabilized via two types of hydrogen bond OW-HW···OW and OW-HW···O as mentioned in table 3b. The sulfate anions play a significant role in the stability of the crystal structure by linking the organic and inorganic cations via N–H···O, C–H···O and OW–HW···O hydrogen bonds (table 3b). Indeed, all the O atoms of the sulfate tetrahedra participate as acceptors in hydrogen bonds. The structure of 2 can be described as an alternation between organic and inorganic layers along the a-axis. On the other hand, the protonated amines are intercalated between the

10

ACCEPTED MANUSCRIPT mineral layers (fig. 3b). The interlayer distance is equal to 12.615 Å, which is equivalent to the half of the a parameter of the crystallographic unit cell. The sulfate groups tie between Co(II)-complexes and protonated cations through N/C-H···O and OW-HW···O hydrogen bond, so they looks as a bridge between the cations networks. The projection of the organic

RI PT

cations in the (b, c) plane are arranged in undulating form. The organic moieties interact with each other by weak π···π interactions. These interactions are of the parallel-displaced configurations [25] as it can be seen in figure 4b.

SC

3. 2. Infrared Spectroscopy

Fig. 5 (a and b) represents the major selected absorptions in the IR spectra of compounds 1 (a)

M AN U

and 2 (b) with their respective assignments. The vibrational bands at 802 and 1109 cm-1 in (a) and 797 and 1124 cm-1 in (b) are due to the asymmetry bending and symmetry stretching vibrations of the SO4 groups. Frequencies in the range 3804-3694 cm-1 in (a) and 3854-3700 cm-1 in (b) are associated to the O-H stretching of either coordinated or uncoordinated water

TE D

molecules. The intense bands situated at 1668 cm-1 in (a) and 1656 cm-1 in (b) can be assigned to the C=C stretching vibrations of the pyridine ring [26]. The observed bands at about 3160 cm-1 (a) and 3001 cm-1 (b) are related to NH2 stretching. The bands which appear in (a) and

EP

(b) at approximately 1477 cm-1 can be assigned to the C-N groups. Additionally, frequencies in the range 1402–1310 cm-1 are attributed to C–C bending of the 2-amino-6-

AC C

methylpyridinium.

3. 3. Thermal decomposition The thermal behavior of compounds 1 and 2 were studied by simultaneous TG-DTA curves fig. 6 (a and b). Hence, these complexes have the same thermal decompositions. TGA curves show a weight losses of about 23.06% starting at room temperature, 25°C, and ending at about 170°C (a) and 145°C (b), which correspond to the removal of the eight water molecules in each material (theoretical weight losses: 23.48%) and leading to anhydrous frameworks of

11

ACCEPTED MANUSCRIPT (C6H9N2)2MII(SO4)2 (MII = Ni and Co). The dehydration of 1 and 2 are accompanied by several endothermic peaks between, at approximately, 107-165°C and 115-140°C, respectively. Furthermore, the departure of these water molecules is done in two steps. It happened before, a small weight loss of about 5.46% (theoretical value, 5.86%) corresponding

RI PT

to the departure of 2H2O and leading to the formation of the intermediate phase unstable (C6H9N2)2MII(SO4)2·6H2O at around 80°C (no plateau on the TG curves). A similar thermal behavior has already been observed for the hybrid materials with the formula

SC

(C7H7N2)2[MII(H2O)6](SO4)2·4H2O (MII = Zn, Cu, Ni and Co) [27]. The second transformations, start at about 170°C (a) and 145°C (b) and ends above 330°C, are assigned to

M AN U

the decomposition of the organic entities with one sulfate group (experimental losses: 61.89% (a); 61.84% (b) and theoretical losses: 62.59% (a); 62.55% (b)) [24, 27]. These decompositions, which observed on the DTA curves, are accompanied by successive endothermic peaks in the range 234 and 317°C in (a) and between 237 and 312°C in (b).

TE D

Then, decompositions go on and end by the formations of the mixture of metal oxides and metal sulfates as final residue [24, 27, 28]. 4.1. BIOLOGICAL ACTIVITIES

EP

4.1.1. Microbial activities

The antibacterial and antifungal activities of the synthesized compounds against

AC C

microorganisms examined in the present study and their potency were qualitatively and quantitatively assessed by the presence or absence of inhibition zones and zone diameter (DD) and the minimal inhibitory concentration (MIC) values (Table 4). All the tested chemical compounds possessed variable antibacterial activity against both Gram negative (Escherichia coli, Pseudomonas aerigunosa and Staphylococus aureus) and Gram positive (Micrococcus luteus and Bacillus subtilis) bacteria and antifungal activity against Aspergilus niger, saccharomyces cerevisiae and Candida albicans. Positive controls produced significant sized

12

ACCEPTED MANUSCRIPT inhibition zones against the tested bacteria and fungi; however, negative control produced no observable inhibitory effect against any of the test organisms as shown in (Table 5). The strongest activity of Co(II) and N(II)-complexes was observed against Staphylococus aureus with a zone of inhibition 26 mm and 23 mm respectively), followed by Micrococcus luteus

RI PT

with a zone of inhibition 23.5 mm and 21 mm respectively. However moderate activities were noted by others microbial strains with a zone of inhibition ranging between 15 mm and 20 mm. Our results suggest that Gram (+) bacteria are more sensitive to the tested chemical

SC

compounds than Gram (-) bacteria, this was consistent with the previous studies reported by H. Lopez-Sandoval et al 2008 [29]. This generally higher resistance among Gram (-) bacteria

M AN U

could be ascribed to the presence of their outer membrane, surrounding the cell wall, which restricts diffusion of hydrophobic compounds through its lipopolysaccharide covering. The absence of this barrier in Gram (+) bacteria allows the direct contact of the complexes 1 and 2 constituents with the phospholipids bilayer of the cell membrane, causing either an increase of

TE D

ion permeability and leakage of vital intracellular constituents, or impairment of the bacterial enzyme systems [30]. For the fungi strains, the disc diameter zones of inhibition ranged from 4.4-11.6 mm with the maximal was obtained by compound 1 against Aspergilus niger

EP

followed by saccharomyces cerevisiae however Candida albicans exhibited weak activity. Our results revealed that Co-complex was more active as antibiotic compound and the Ni-

AC C

complex was more active as a fungicide, It is therefore reasonable to assume that use as a therapeutic compounds. The antimicrobial results suggested that all the complexes were found to be biologically active and their metal complexes showed significantly enhanced antibacterial and antifungal activities against microbial tested strains in comparison to the free ligands. Chohan et al., in 2001 and 2004, [31, 32], were suggested that chelation tended to make the ligands deed as more powerful bactereostatic agents, thus inhibiting the growth of bacteria more than the parent ligands. It was suspected that factors such as solubility,

13

ACCEPTED MANUSCRIPT conductivity, dipole moment and cell permeability mechanism influenced by the presence of metal ion might be the possible reason for the increase in activity. 4.1.2. Antioxidant assay Antioxidant assay of synthesized compounds and its metal complexes were evaluated for

RI PT

DPPH radical scavenging, Total antioxidant and reducing power activity (figures 7, 8 and 9), which are well-known methods, to some degree complementary, which indicate the host’s total capacity to withstand free-radical stress. It is well known that reactive oxygen species

SC

(ROS) formed during biochemical processes in body system, are vastly reactive and potentially damaging transient chemical species. The oxidative damages caused by ROS on

M AN U

lipids, proteins, and nucleic acids may generate various chronic diseases [33]. Hence, to prevent the free radical damage in the body, it is important to administer drugs that may be rich in antioxidants. In this study, the metal complexes showed good activities as a radical scavenger compared with ascorbic acid (vitamin C), figure 7. These results were in agreement

TE D

with previous metallic complexes studies, where the ligand has an antioxidant potential and it is expected that the metal moiety will increase its activity [34]. Both the compounds exhibited high total antioxidant capacity, they possess an almost equal potential, but the capacity of the

EP

Co complex was observed to be a little higher than its corresponding Ni complex by 84.39 %, and 75.69 % respectively. The DPPH scavenging activity of complex 2 is significantly higher

AC C

than that of 1 (81.54 % and 70.59 % respectively) indicating that the cobalt complex is a better free radical scavenger and antioxidant but lower when compared to ascorbic acid (vitamin C) as standard. Radical scavenging activity of metal complexes as well as the standards was increased in a dose-dependent manner. The results presented above are in line with those described by AKILA et al 2013, [33], which have been reported that all the metal complexes showed comparable or slight less activity to that of standard (Ascorbic acid). The copper complex showed significantly higher DPPH activity followed by Nickel and vanadium

14

ACCEPTED MANUSCRIPT complexes. Therefore, the results obtained from this study provide linkage to the use of the synthesized compounds in the treatment of pathological diseases arising from oxidative stress.

5. Conclusion As demonstrated above, the metal ion complexes of the 2-amino-6-methylpyridine ligand

RI PT

were characterized by using different physico-chemical techniques and biological methods. The structures show a lamellar stacking of supramolecular inorganic layers for which the interlayer space is filled with aromatic amines that form chains through π···π interactions. As

SC

a consequence, the interlayer distances depend on the nature of the transition metal and the interaction types between the organic and inorganic components. The interspaces can be also

M AN U

strongly dependent on the nature and the arrangement of the amine integrated between two mineral layers. All M(II) complexes tested by in vitro anti-microbial, anti-fungal and antioxidant activity which shows fine results with an enhancement of activity on complexation with metal ions. In review, such biological activities testing results reveal that complexes

TE D

possess higher activity compared to parent ligand due to presence of the metals. NOTES

The authors declare no competing financial interest.

EP

ASSOCIATED CONTENT

AC C

Supporting Information:

Crystallographic data for complexes 1 and 2, are available from the Cambridge Crystallographic Data Centre, with CCDC No. 1039274, for compound 1, and No. 1433263 for compound 2. Copies of these data can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223 336-033; or e-mail: [email protected]. Acknowledgments

15

ACCEPTED MANUSCRIPT The authors thank Pr. Abdelmottaleb OUEDERNI for his assistance in TGA/DTA measurements of this study (The Unit of Joint Service of Research–National School of Engineers of Gabes, University of Gabes, Tunisia).

References

RI PT

[1] (a) O. M. Yaghi, M. O’Keeffe, N. W. Ockwig, H. K. Chae, M. Eddaoudi, J. Kim, Nature. 423 (2003) 705; (b) B. Moulton, M. J. Zaworotko, Chem. Rev. 101 (2001) 1629; (c) M. Du, C. P. Li, C-S. Liu, S-M. Fang, Coord. Chem. Rev. 257 (2013) 1282.

SC

[2] G. R. Desiraju, Angew. Chem. Int. Ed. Engl. 34 (1995) 2311.

[3] T. Kusukawa, M. Fujita, J. Am. Chem. Soc. 121 (1999) 1397.

M AN U

[4] M. Fujita, S-Y. Su, T. Kusukawa, H. Funaki, K. Ogura, K. Yamaguchi, Angew. Chem. Int. Ed. 37 (1998) 2082.

[5] F. Baumann, A. Livoreil, W. Kaim, J-P. Sauvage, Chem. Commun. 1 (1997) 35. [6] D. B. Amabilino, C. O. Dietrich-Buchecker, A. Livoreil, L. Perez-Garcia, J-P. Sauvage, J.

TE D

F. Stoddart, J. Am. Chem Soc. 118 (1996) 3905.

[7] Z. H. Chohan, C. T. Supran, J. Enz. Inhib. Med. Chem. 20 (2005) 463. [8] Z. H. Chohan, C. T. Supran, A. Scozzafava, J. Enz. Inhib. Med. Chem. 19 (2004) 79.

EP

[9] K. Singh, Y. Kumar, R. K. Pundir, Synth. React. Inorg. Met. Org. Chem. 40 (2010) 836.

AC C

[10] A. Altundas, S. Nursen, N. Colak, H. Ogutchi, Med. Chem. Res. 19 (2010) 576. [11] Z. H. Chohan, M. Praveen, A. Ghaffar, Metal-Based Drugs. 4(5) (1997) 267. [12] V. K. Patel, A. M. Vasanwala, C. N. Jejurkar, Indian Journal of Chemistry. 28A (1989) 719.

[13] M. J. Cleare, J. D. Hoeschele, Bioinorganic Chemistry. 2(3) (1973) 187. [14] V. A. Narayanan, M. Nasr, K. D. Paull, In: Tin Based Antitumour Drugs. Vol H (1990) 37. Berlin, Germany: Springer; NATO ASI Series.

16

ACCEPTED MANUSCRIPT [15] CrysalisPRO and CrysAlisRED in Xcalibur R software, Agilent Technologies Inc., Yarnton, Oxfordshire, UK. [16] G. M. Sheldrick, Acta Cryst. A64 (2008) 112.

[18] M. S. Blois, Nature. 26 (1958) 1199.

RI PT

[17] K. Brandenburg, Diamond. Version 3.2i., 2012, Crystal Impact GbR, Bonn, Germany.

[19] P. Prieto, M. Pineda, M. Aguilar, Anal. Biochem. 269 (1999) 337. [20] M. Oyaizu, Japanese Journal of Nutrition. 44 (1986) 307.

SC

[21] K. Singh, Y. Kumar, P. Puri, C. Sharma, K. R. Aneja, Arabian Journal of Chemistry, 2013, doi:10.1016/j.arabjc.2012.12.038.

M AN U

[22] D. Wade, A. Silveira, L. Rollins-Smith, T. Bergman Silberring, J. Acta. Biochim. Pol. 48 (2001) 1185.

[23] F. Hajlaoui, H. Naïli, S. Yahyaoui, A. J. Norquist, T. Mhiri, T. Bataille, Journal of Organometallic Chemistry. 700 (2012) 110.

40 (2011) 11613.

TE D

[24] F. Hajlaoui, H. Naïli, S. Yahyaoui, M. M. Turnbull, T. Mhiri, T. Bataille, Dalton Trans.

[25] N. J. Singh, S. K. Min, D. Y. Kim, K. S. Kim, J. Chem. Theory. Comput. 5 (2009) 515.

EP

[26] Z. Liu, Q. Liu, X. Dai, C. Shen-Tu, C. Yao, Y. Kong, ECS. Electrochem. Lett. 2 (2013) G1.

AC C

[27] O. Kammoun, W. Rekik, H. Naïli, T. Bataille, New J. Chem. 39 (2015) 2682. [28] O. Kammoun, H. Naïli, W. Rekik, T. Bataille, Inorganica Chimica Acta (2015), doi: http://dx.doi.org/10.1016/j.ica.2015.05.031. [29] H. Lopez-Sandoval, M.E. Londono-Lemos, R. Garza-Velasco, I. Poblano-Melendez, P. Granada-Macias, I. Gracia-Mora, N. Barba-Behrens, Journal of Inorganic Biochemistry. 102 (2008) 1267.

17

ACCEPTED MANUSCRIPT [30] Z. Zarai, A. Kadri, I. Ben Chobba, R. Ben Mansour, A. Bekir, H. Mejdoub, N. Gharsallah, Lipids Health Dis. 10 (2011) 161. [31] Z. H. Chohan, M. Praveen, Appl. Organomet. Chem. 15 (2001) 617. [32] Z. H. Chohan, C. T. Supran, A. Scozzafava, J. Enz. Inhib. Med. Chem. 19 (2004) 79.

Pharmaceutical Sciences. 5(2) (2013) 573.

RI PT

[33] E. Akila, M. Usharani, R. Rajavel, International Journal of Pharmacy and

[34] A. A. H. Kadhum, A. B. Mohamad, A. A. Al-Amiery, M. S. Takriff, Molecules. 16(8)

AC C

EP

TE D

M AN U

SC

(2011) 6969.

18

ACCEPTED MANUSCRIPT Figure captions Fig. 1a: Part of the crystal structure of compound 1 at 100 K showing the asymmetric unit and atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds are represented by dashed lines, [Ni1 and Ni2 octahedron are completed by

RI PT

symmetry, symmetry code: i = −x+1,−y+1, −z+1 and ii = −x,−y+1,−z; respectively]. Fig. 2a: Hydrogen bonding between the inorganic entities within the mineral layer in compound 1, showing its supramolecular aspect.

SC

Fig. 3a: Projection of the structure along the crystallographic c-axis in compound 1, showing the lamellar character and the stacking along the a-axis (hydrogen atoms are omitted for

M AN U

clarity).

Fig. 4a: Offset-face-to-face interactions motifs (π···π stacking, broken lines) in the cation chains along the crystallographic b-axis in 1.

Fig. 1b: Part of the crystal structure of compound 2 at 100 K showing the asymmetric unit

TE D

and atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds are represented by dashed lines, [Co2 and Co3 octahedron are completed by symmetry, symmetry code: i = −x,−y+2,−z; ii = −x,−y+2,−z+1; respectively].

EP

Fig. 1c: Disorder of the organic cation (C6H9N2)+. Fig. 2b: Hydrogen bonding between the inorganic entities within the mineral layer in

AC C

compound 2, showing its supramolecular aspect. Fig. 3b: Projection of the structure along the crystallographic c-axis in compound 2, showing the lamellar character and the stacking along the b-axis (hydrogen atoms are omitted for clarity). Fig. 4b: Offset-face-to-face interactions motifs (π···π stacking, broken lines) in the cation chains along the crystallographic a-axis in 2. Fig. 5: Infrared absorption spectra of Ni (a) and Co (b) compounds.

19

ACCEPTED MANUSCRIPT Fig. 6: Simultaneous thermogravimetric analysis and differential thermal analysis scan for compounds 1 (a) and 2 (b). The scan was performed in flowing air with a ramp rate of 5°C/min. Fig. 7: DPPH free radical-scavenging activity of synthesized compounds 1 and 2 at different

RI PT

concentrations.

Fig. 8: Total antioxidant activity of synthesized compounds 1 and 2 at different concentrations.

SC

Fig. 9: Reducing power of synthesized compounds 1 and 2 at different concentrations.

M AN U

Table captions

Table 1: Crystallographic data and structure refinement parameters for compounds 1 and 2. Table 2a: Selected bond distances (Å) and angles (°) in compound 1. Table 3a: Hydrogen bonding geometry (Å, °) for compound 1.

TE D

Table 2b: Selected bond distances (Å) and angles (°) in compound 2. Table 3b: Hydrogen bonding geometry (Å, °) for compound 2. Table 4: Antibacterial activity of synthesized compounds 1 and 2 using agar disc diffusion.

AC C

EP

Table 5: Antifungal activity of synthesized compounds 1 and 2 using agar disc diffusion.

20

ACCEPTED MANUSCRIPT

M AN U

SC

RI PT

Figures

AC C

EP

TE D

Figure 1a

Figure 2a

21

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

Figure 3a

Figure 4a 22

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

Figure 1b

Figure 1c

23

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

Figure 2b

Figure 3b

24

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

Figure 4b

Figure 5

25

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

(a)

(b) Figure 6

26

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

Figure 7

Figure 8

27

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

Figure 9

28

ACCEPTED MANUSCRIPT Tables Table 1 Compound 1 (C6H9N2)2[Ni(H2O)6](SO4)2·2H2O 1226.52 100(2) Triclinic P

Compound 2 (C6H9N2)2[Co(H2O)6](SO4)2·2H2O 1226.96 100(2) Monoclinic P 21/c

a(Å) b (Å) c (Å) α (°) β (°) γ (°) V (Å3) Z Diffractometer Programs system Absorption correction ρcal (g cm-3) Crystal size (mm3) Crystal color/shape µ (mm−1) θ range (deg) hkl range

7.3606(18) 13.213(3) 13.897(3) 106.72(2) 105.03(2) 98.69(2) 1212.4(5) 2 Kuma KM-4-CCD SHELXL-2013 and SHELXS-97 Analytical 1.680 0.37× 0.31× 0.24 GREEN, BLOCK 1.050 θmin = 2.87, θmax = 36.71 -12 ≤ h ≤ 9 -19 ≤ k ≤ 21 -23≤ l ≤ 23 9162 7660 644 0.0373 0.1098 1.132 321 Tmin= 0.685; Tmax= 0.737 ∆ρmin = -0.533, ∆ρmax = 0.856

25.231(6) 13.844(3) 14.728(4) 90 103.46(2) 90 5003(2) 8 Xcalibur, Ruby SHELXL-2013 and SHELXS-97 Analytical 1.629 0.50 × 0.45 × 0.35 PINK, BLOCK 0.932 θmin = 3, θmax = 36.81 -36 ≤ h ≤ 41 -22 ≤ k ≤ 23 -19 ≤ l ≤ 24 20448 16550 2568 0.0664 0.1524 1.253 671 Tmin= 0.634; Tmax= 0.722 ∆ρmin = -0.939, ∆ρmax = 1.313

AC C

EP

No. of reflection collected No. of independant reflection F(000) R1 wR2 GooF No. param. Transmission factors Largest difference map hole

TE D

M AN U

SC

RI PT

Structural parameter Formula Formula weight (g mol-1) Temperature (K) Crystal system Space group

Table 2a

29

ACCEPTED MANUSCRIPT

RI PT

Within the organic moieties N1A–C2A 1.3454 (18) N1A–C6A 1.3729 (17) N2A–C2A 1.3415 (17) C2A–C3A 1.4136 (18) C3A–C4A 1.3769 (19) C4A–C5A 1.406 (2) C5A–C6A 1.3682 (18) C6A–C7A 1.491 (2) C2A–N1A–C6A 123.44 (11) N2A–C2A–N1A 118.90 (12) N2A–C2A–C3A 122.39 (13) N1A–C2A–C3A 118.71 (12) C4A–C3A–C2A 118.50 (13) C3A–C4A–C5A 121.26 (12) C6A–C5A–C4A 118.95 (12) C5A–C6A–N1A 119.13 (13) C5A–C6A–C7A 124.44 (12) N1A–C6A–C7A 116.43 (11) N1B–C2B 1.3497 (18) N1B–C6B 1.3698 (18) N2B–C2B 1.3379 (18) C2B–C3B 1.4134 (19) C3B–C4B 1.375 (2) C4B–C5B 1.406 (2) C5B–C6B 1.3712 (19) C6B–C7B 1.491 (2) C2B–N1B–C6B 123.85 (11) N2B–C2B–N1B 118.87 (12) N2B–C2B–C3B 122.73 (14) N1B–C2B–C3B 118.40 (12) C4B–C3B–C2B 118.61 (13) C3B–C4B–C5B 121.29 (12) C6B–C5B–C4B 119.10 (13) N1B–C6B–C5B 118.75 (13) N1B–C6B–C7B 116.73 (11) C5B–C6B–C7B 124.52 (12)

AC C

EP

TE D

M AN U

SC

Compound 1 Octahedron around Ni Tetrahedron around S1 and S2 Ni1–OW1 2.0592 (10) S1–O1 1.4946 (10) Ni1–OW1i 2.0592 (10) S1–O2 1.4927 (11) Ni1–OW2 2.0551 (12) S1–O3 1.4676 (10) Ni1–OW2i 2.0551 (12) S1–O4 1.4667 (11) Ni1–OW3 2.0698 (10) O2–S1–O1 107.32 (6) Ni1–OW3i 2.0698 (10) O4–S1–O1 109.09 (6) Ni2–OW4 2.0454 (10) O3-S1–O1 109.70 (6) Ni2–OW4ii 2.0454 (10) O4–S1–O2 110.54 (6) Ni2–OW5 2.0414 (10) O3–S1–O2 109.52 (6) Ni2–OW5ii 2.0414 (10) O3-S1-O4 110.61 (7) Ni2–OW6 2.0514 (12) S2–O5 1.4762 (10) Ni2–OW6ii 2.0514 (12) S2–O6 1.4845 (11) OW2–Ni1–OW1 89.66 (5) S2–O7 1.4913 (11) OW2i–Ni1–OW1i 89.66 (5) S2–O8 1.4674 (10) OW2i–Ni1–OW1 90.34 (5) O8–S2–O5 110.41 (6) OW2i–Ni1–OW2 180 O8–S2–O6 109.93 (6) 90.34 (5) O5–S2–O6 108.74 (7) OW2–Ni1–OW1i OW1–Ni1–OW1i 180 O8–S2–O7 109.25 (6) OW2i–Ni1–OW3i 88.36 (4) O5–S2–O7 108.75 (6) OW2–Ni1–OW3i 91.64 (4) O6–S2–O7 109.75 (6) OW1–Ni1–OW3i 90 OW1i–Ni1–OW3i 90 OW2i–Ni1–OW3 91.64 (4) OW2–Ni1–OW3 88.36 (4) OW1–Ni1–OW3 90 OW1i–Ni1–OW3 90 OW3i–Ni1–OW3 180 OW5–Ni2–OW5ii 180 OW5–Ni2–OW4ii 87.83 (4) OW5ii–Ni2–OW4ii 92.17 (4) OW5–Ni2–OW4 92.17 (4) OW5ii–Ni2–OW4 87.83 (4) OW4ii–Ni2–OW4 180 OW5–Ni2–OW6 85.95 (5) OW5ii–Ni2–OW6 94.05 (5) OW4ii–Ni2–OW6 88.89 (4) OW4–Ni2–OW6 91.11 (4) OW5–Ni2–OW6ii 94.05 (5) OW5ii–Ni2–OW6ii 85.95 (5) OW4ii–Ni2–OW6ii 91.11 (4) OW4–Ni2–OW6ii 88.89 (4) OW6–Ni2–OW6ii 180 Symmetry codes: (i) = −x+1,−y+1, −z+1; (ii) = −x,−y+1,−z.

30

ACCEPTED MANUSCRIPT Table 3a d(H–D) (Å)

Compound 1 d(H···A) (Å)

d(D···A) (Å)

OW1–H1W1···O6 OW1–H2W1···O2 OW2–H1W2···O1 OW2–H2W2···O7i OW3–H1W3···OW7 OW3–H2W3···O1iii OW4–H1W4···O2 OW4–H2W4···OW8 OW5–H1W5···O5iv OW5–H2W5···OW7i OW6–H1W6···O5 OW6–H1W6···O6 OW6–H2W6···OW8v N1A–H1A···O8 N2A–H2A···O6 N2A–H2B···O7iv C3A–H3A···O8iv C5A–H5A···OW2vi C5A–-H5A···OW3vi C7A–H7C···O3vii N1B–H1B···O3 N2B–H2C···O2 N2B–H2D···O4iii C3B–H3B···O3iii C5B–H5B···OW4viii C7B–H7E···O8ix OW7–H1W7···O7x OW7–H2W7···O1i OW8–H1W8···O4iii OW8–H2W8···O5

0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.87 0.86 0.86 0.86 0.86 0.86 0.88 0.88 0.88 0.95 0.95 0.95 0.98 0.88 0.88 0.88 0.95 0.95 0.98 0.86 0.86 0.86 0.86

1.91 1.94 1.89 1.88 1.87 2.06 1.88 1.86 1.89 2.02 2.55 2.12 1.96 1.83 2.07 2.31 2.50 2.62 2.56 2.59 1.85 2.10 2.04 2.64 2.48 2.65 1.85 1.90 1.89 1.96

2.765(14) 2.786(18) 2.750(17) 2.737(14) 2.722(17) 2.874(14) 2.728(14) 2.720(16) 2.722(15) 2.809(14) 3.071(17) 2.973(16) 2.798(15) 2.710(15) 2.950(16) 3.175(18) 3.357(2) 3.358(17) 3.455(2) 3.232(18) 2.721(15) 2.965(17) 2.914(18) 3.483(2) 3.349(2) 3.367(18) 2.702(15) 2.751(15) 2.726(15) 2.818(16)

SC

M AN U TE D

∠ D–H···A(°) 171 169 177 174 173 157 172 175 164 152 120 174 165 174 177 169 150 135 158 123 172 170 171 148 152 130 171 169 164 172

RI PT

D–H···A

AC C

EP

Symmetry codes: (i) = −x+1,−y+1,−z+1; (iii) = x+1, y, z; (iv) = x−1, y, z; (v) = −x+1,−y+1,−z; (vi) = x, y+1, z; (vii) = x+1,y+1, z; (viii) = −x,−y,−z; (ix) = x−1,y−1,z; (x) = −x+2,−y+1,−z+1.

31

ACCEPTED MANUSCRIPT Table 2b

RI PT

Within the organic moieties N1A–C2A 1.343 (4) N1A–C6A 1.373 (4) N2A–C2A 1.336 (4) C2A–C3A 1.424 (4) C3A–C4A 1.370 (4) C4A–C5A 1.406 (5) C5A–C6A 1.376 (4) C6A–C7A 1.494 (4) C2A–N1A–C6A 123.9 (2) N2A–C2A–N1A 119.1 (3) N2A–C2A–C3A 122.7 (3) N1A–C2A–C3A 118.2 (3) C4A–C3A–C2A 118.6 (3) C3A–C4A–C5A 121.6 (3) C6A–C5A–C4A 118.7 (3) N1A–C6A–C5A 118.9 (3) N1A–C6A–C7A 117.0 (3) C5A–C6A–C7A 124.1 (3) N1B–C2B 1.354 (4) N1B–C6B 1.369 (4) N2B–C2B 1.338 (4) C2B–C3B 1.414 (4) C3B–C4B 1.370 (4) C4B–C5B 1.408 (4) C5B–C6B 1.366 (4) C6B–C7B 1.495 (4) C2B–N1B–C6B 123.7 (2) N2B–C2B–N1B 119.2 (3) N2B–C2B–C3B 122.5 (3) N1B–C2B–C3B 118.3 (3) C4B–C3B–C2B 118.6 (3) C3B– C4B–C5B 121.4 (3) C6B–C5B–C4B 119.1 (3) C5B–C6B–N1B 118.9 (3) C5B–C6B–C7B 124.7 (3) N1B–C6B–C7B 116.4 (3) N2C–C2C 1.344 (4) N1C–C2C 1.354 (4) N1C–C6C 1.364 (4) C2C–C3C 1.408 (4) C3C–C4C 1.372 (4) C4C–C5C 1.410 (4) C5C–C6C 1.360 (4) C6C–C7C 1.499 (4) C2C–N1C–C6C 123.6 (2) N2C–C2C–N1C 118.9 (3) N2C–C2C–C3C 122.7 (3) N1C–C2C–C3C 118.4 (3) C4C–C3C–C2C 118.5 (3) C3C–C4C–C5C 121.4 (3) C6C–C5C–C4C 118.8 (3) C5C–C6C–N1C 119.3 (3) C5C–C6C–C7C 124.5 (3) N1C–C6C–C7C 116.2 (3) N2D–C2D 1.334 (8) N1D–C2D 1.348 (11) N1D–C6D 1.374 (7)

TE D

M AN U

SC

Compound 2 Tetrahedron around S1, S2, S3 and S4 S1–O11 1.469 (2) S1–O21 1.475 (2) S1–O31 1.481 (2) S1–O41 1.495 (2) O11–S1–O12 109.51 (13) O11–S1–O13 110.49 (14) O12–S1–O13 108.73 (13) O11–S1–O14 109.30 (12) O12–S1–O14 110.20 (13) O13–S1–O14 108.61 (13) S2–O21 1.484 (2) S2–O22 1.464 (2) S2–O23 1.481 (2) S2–O24 1.492 (2) O22–S2–O23 110.61 (13) O22–S2–O21 110.04 (13) O23–S2–O21 110.18 (13) O22–S2–O24 110.33 (14) O23–S2–O24 107.86 (14) O21–S2–O24 107.76 (13) S3–O33 1.464 (3) S3–O32 1.470 (3) S3–O34 1.483 (2) S3–O31 1.488 (2) O33–S3–O32 109.49 (16) O33–S3–O34 110.27 (17) O32–S3–O34 109.53 (14) O33–S3–O31 110.20 (15) O32–S3–O31 109.30 (16) O34–S3–O31 108.02 (13) S4-O41 1.473(2) S4-O42 1.459(2) S4-O43 1.475(2) S4-O44 1.480(3) O42-S4-O43 110.50 (15) O42-S4-O41 110.23 (15) O43-S4-O41 111.31 (15) O42-S4-O44 109.42 (18) O43-S4-O44 107.24 (19) O41-S4-O44 108.04 (15)

AC C

EP

Octahedron around Co Co1–OW1 2.120 (2) Co1–OW2 2.074 (2) Co1–OW3 2.069 (2) Co1–OW4 2.115 (2) Co1–OW5 2.063 (2) Co1–OW6 2.096 (2) Co2–OW7 2.096 (2) Co2–OW7i 2.096 (2) Co2–OW8 2.078 (2) Co2–OW8i 2.078 (2) Co2–OW9 2.118 (2) Co2–OW9i 2.118 (2) Co3–OW10 2.065 (2) Co3–OW10ii 2.065 (2) Co3–OW11 2.084 (2) Co3–OW11ii 2.084 (2) Co3–OW12 2.115 (2) Co3–OW12ii 2.115 (2) OW2–Co1–OW6 93.78 (9) OW5–Co1–OW4 90.93 (10) OW3–Co1–OW4 89.87 (9) OW2–Co1–OW4 177.83 (9) OW6–Co1–OW4 86.02 (9) OW5–Co1–OW1 87.85 (8) OW3–Co1–OW1 88.26 (8) OW2–Co1–OW1 87.92 (9) OW6–Co1–OW1 177.74 (9) OW4–Co1–OW1 92.24 (9) 180 OW8–Co2–OW8i OW8–Co2–OW7i 90.85 (9) OW8i–Co2–OW7i 89.15 (9) OW8–Co2–OW7 89.15 (9) 90.85 (9) OW8i–Co2–OW7 OW7i–Co2–OW7 180 88.48 (9) OW8–Co2–OW9 91.52 (9) OW8i–Co2–OW9 89.09 (9) OW7i–Co2–OW9 90.91 (9) OW7–Co2–OW9 91.52 (9) OW8–Co2–OW9i 88.48 (9) OW8i–Co2–OW9i 90.91 (9) OW7i–Co2–OW9i 89.09 (9) OW7–Co2–OW9i 180 OW9–Co2–OW9i 180 OW10ii–Co3–OW10 89.12 (9) OW10ii–Co3–OW11 90.88 (9) OW10–Co3–OW11 90.88 (9) OW10ii–Co3–OW11ii 89.12 (9) OW10–Co3–OW11ii 180 OW11–Co3–OW11ii 88.60 (9) OW10ii–Co3–OW12ii 91.40 (9) OW10–Co3–OW12ii 89.84 (9) OW11–Co3–OW12ii 90.16 (9) OW11ii–Co3–OW12ii 91.40 (9) OW10ii–Co3–OW12 88.60 (9) OW10–Co3–OW12 90.16 (9) OW11–Co3–OW12 89.84 (9) OW11ii–Co3–OW12

32

ACCEPTED MANUSCRIPT 180

C2D–C3D C3D–C4D C4D–C5D C5D–C6D C6D–C7D C2D–N1D–C6D N2D–C2D–N1D N2D–C2D–C3D N1D–C2D–C3D C4D–C3D–C2D C3D–C4D–C5D C6D–C5D–C4D C5D–C6D–N1D C5D–C6D–C7D N1D–C6D–C7D N2E–C2E N1E–C2E N1E–C6E C2E–C3E C3E–C4E C4E–C5E C5E–C6E C6E–C7E C2E–N1E–C6E N2E–C2E–N1E N2E–C2E–C3E N1E–C2E–C3E C4E–C3E–C2E C3E–C4E–C5E C6E–C5E–C4E N1E–C6E–C5E N1E–C6E–C7E C5E–C6E–C7E

1.407 (11) 1.373 (9) 1.402 (8) 1.363 (6) 1.503 (7) 122.7 (6) 118.0 (12) 123.6 (12) 118.4 (7) 119.5 (8) 120.3 (6) 119.3 (5) 119.5 (5) 124.7 (5) 115.8 (5) 1.338 (12) 1.357 (16) 1.365 (12) 1.414 (15) 1.376 (11) 1.396 (9) 1.365 (10) 1.503 (9) 121.6 (12) 117.6 (18) 122.7 (18) 119.5 (12) 118.3 (10) 120.9 (8) 119.3 (7) 120.2 (9) 115.6 (9) 124.2 (8)

TE D

M AN U

SC

RI PT

OW12ii–Co3–OW12

AC C

EP

Symmetry codes: (i) = −x,−y+2,−z; (ii) = −x,−y+2,−z+1.

Table 3b 33

ACCEPTED MANUSCRIPT

2.791(3) 2.790(3) 2.663(3) 2.751(3) 2.773(3) 2.689(3) 2.725(3) 2.804(3) 2.747(3) 2.656(3) 2.892(3) 2.666(3) 2.688(3) 2.788(3) 2.747(3) 2.777(3) 2.943(3) 2.781(3) 2.751(3) 2.712(3) 2.830(3) 2.722(3) 3.060(3) 3.170(3) 2.727(3) 2.709(3) 2.933(3) 3.447(2) 3.414(3) 2.768(3) 2.969(3) 2.831(4) 3.445(4) 3.420(4) 2.936(3) 2.949(3) 2.697(4) 3.439(4) 3.345(4) 2.736(4) 2.807(4) 2.782(3) 2.696(3) 2.782(3) 2.857(3) 2.743(4) 3.239(4) 2.756(4) 2.931(3) 2.892(3) 2.869(17) 3.222(16) 3.290(3) 2.99(3) 2.83(4) 2.920(5) 3.192(3) 3.281(3)

∠ D–H···A(°) 176 170 155 173 167 162 170 176 164 169 161 170 173 163 172 176 156 157 178 171 178 177 151 132 175 173 166 151 159 171 170 151 158 161 153 170 169 155 159 174 173 167 168 167 170 172 140 157 157 169 166 165 161 172 174 169 158 154

RI PT

1.93 1.94 1.86 1.90 1.93 1.86 1.87 1.95 1.91 1.81 2.06 1.81 1.83 1.95 1.89 1.92 2.14 1.97 1.89 1.86 1.97 1.86 2.28 2.53 1.87 1.83 2.07 2.58 2.51 1.90 2.10 2.03 2.55 2.51 2.12 2.08 1.83 2.56 2.44 1.88 1.95 1.94 1.85 1.94 2.01 1.89 2.54 1.94 2.10 2.02 2.01 2.29 2.38 2.11 1.95 2.05 2.29 2.40

d(D···A) (Å)

SC

0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.88 0.88 0.95 0.95 0.88 0.88 0.88 0.95 0.95 0.88 0.88 0.88 0.95 0.95 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.86 0.88 0.88 0.88 0.95 0.95 0.88 0.88 0.88 0.95 0.95

AC C

OW1–H1W1···O21 OW1–H1W2···O23iv OW2–H2W1···O44iii OW2–H2W2···OWAiv OW3–H3W1···OWAv OW3–H3W2···OWC OW4–H4W1···O43vi OW4–H4W2···O24 OW5–H5W1···O24iii OW5–H5W2···O41vii OW6–H6W1···O23 OW6–H6W2···OWCvii OW7–H7W1···O13 OW7–H7W2···O31viii OW8–H8W1···OWBix OW8–H8W2···O34 OW9–H9W1···OWDviii OW9–H9W2···O14i OW10–HW10···O34viii OW10–HW11···O14viii OW11–HW13···O31viii OW11–HW14···OWD OW12–HW15···O32 OW12–HW15···N2E OW12–HW16···OWBix N1A–H1A···O11x N2A–H2A1···O14x C3A–H3A···O11xi C5A–H5A···OW3iv N1B–H1B···O22 N2B–H2B1···O23 N2B–H2B2···O41vii C3B–H3B···O42vii C5B–H5B···OW8 N2C–H2C1···O43xii N2C–H2C2···O21 N1C–H1C···O42xii C3C–H3C···O22 C5C–H5C···OW11ii OWA–HWA1···O21 OWA–HWA2···O24v OWB–HWB1···O31xi OWB–HWB2···O12xi OWC–HWC1···O44 OWC–HWC2···O43vi OWD–HWD1···O32 OWD–HWD2···O12 OWD–HWD2···O13 N2D–H2D1···O32 N2D–H2D2···O34xiii N1D–H1D···O33 C3D–H3D···O33xiii C5D–H5D···OW5xiii N2E–H2E1···O34xiii N2E–H2E2···O32 N1E–H1E···O33xiii C3E–H3E···O33 C5E–H5E···OW4xiii

TE D

iii

Compound 2 d(H···A) (Å)

M AN U

d(H–D) (Å)

EP

D–H···A

34

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

Symmetry codes: (i) = −x,−y+2,−z; (ii) = −x,−y+2,−z+1; (iii) = x,−y+3/2,z−1/2; (iv) = −x+1,y−1/2,−z+1/2; (v) = −x+1,−y+2,−z+1; (vi) = −x+1,−y+1,−z+1; (vii) = −x+1,y+1/2,−z+1/2; (viii) = −x,y+1/2,−z+1/2; (ix) = x,y+1,z; (x) = −x,−y+1,−z; (xi) = −x,y−1/2,−z+1/2; (xii) = −x+1,y+1/2,−z+3/2; (xiii) = x,−y+3/2,z+1/2.

35

ACCEPTED MANUSCRIPT Table 4

DD (2)

DD (1)

DD (Control)

MIC (mg/ml)

Escherichia coli

20 ± 0.7

18.6± 0.5

21 ± 1.1

10-1

-

-

28 ± 0.6

NA

Bacillus subtilis

21 ± 0.9

20.2 ± 0.8

26 ± 0.6

10-4

Pseudomonas aerigunosa

17.6 ± 1.2

15.5 ± 0.7

19.6 ± 1

10-3

Staphylococus aureus

26 ± 0.5

22 ± 0.3

Micrococcus luteus

23.5 ± 0.7

21 ± 1.0

SC

M AN U

Salmonella enterica

RI PT

Strains

28 ± 0.6

10-4

23 ± 0.4

10-2

TE D

Values are expressed as mean ± standard deviation (n = 3) DD (2) (1) : Disc Diameter of inhibition (halo size) in (mm) of Cobalt, Nickel respectively… DD (controls): Disc Diameter of inhibition zone of ampicillin (10 µg/disc) was used as positive control , MIC: minimum inhibitory concentration (mg/ml), (−) no activity.

Table 5

DD (2)

DD (1)

DD (Control)

MIC (mg/ml)

10.62± 0.5

11.6 ± 0.5

22 ± 0.5

10-3

saccharomyces cerevisiae

7.9 ± 0.6

9 ± 0.5

18.3 ± 1.0

10-1

Candida albicans

4.4 ± 0.7

6.4 ± 0.0

10.6± 0.6

10-2

AC C

Aspergilus niger

EP

Strains

Values are expressed as mean ± standard deviation (n = 3) DD (2) (1) : Disc Diameter of inhibition (halo size) in (mm) of Cobalt, Nickel respectively… DD (controls): Disc Diameter of inhibition zone of cycloheximide (10 µg/disc), was used as positive control, MIC: minimum inhibitory concentration (mg/ml), (−) no activity

36

ACCEPTED MANUSCRIPT

M AN U

SC

RI PT

Graphical Abstract

Highlights


We have successfully designed and synthesized two new supramolecular hybrid

TE D

sulfate complexes templated by 2-amino-6-methylpyridinium.
The interlayer space is filled with aromatic amines that form chains through π···π interactions.

EP


The structural diversity and the thermal investigation were also discussed.

AC C


The in vitro antibacterial and antifungal activities of these compounds were evaluated.
The antioxidant activities of the complexes were investigated through scavenging effect on DPPH radicals, total antioxidant activity and reducing power.

37