Syntheses and Photophysical Properties of Schiff ... - ACS Publications

Research Article pubs.acs.org/journal/ascecg

Syntheses and Photophysical Properties of Schiff Base Ni(II) Complexes: Application for Sustainable Antibacterial Activity and Cytotoxicity Pushap Raj,† Amanpreet Singh,† Ajnesh Singh,‡ and Narinder Singh*,† †

Department of Chemistry, Indian Institute Technology Ropar, Punjab 140001, India Department of Applied Sciences and Humanities, Jawaharlal Nehru Government Engineering College, Sundernagar, Mandi, Himachal Pradesh 175018, India

Downloaded via UNIVERSITE DE SHERBROOKE on July 10, 2018 at 19:06:56 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

‡

S Supporting Information *

ABSTRACT: Five new imine-linked ligands (H2L1, H4L2, and L3− L5) were synthesize in two step reactions and final products were fully characterized with spectroscopic techniques. The binding behavior of these ligands was evaluated with the library of metal ions. However, substantial photophysical modulations were observed with the coordination of [Ni2+] ion to the ligand pocket. The fact that Ni2+ induced remarkable modulation in photophysical studies encouraged us to prepare the nickel complexes of respective ligands. The resultant coordination complexes offered interesting properties like tunable coordination geometry, variable stereochemistry, and possibility of electrostatic interactions which are important for biomolecular recognition. These properties of coordination complexes encouraged us to evaluate the antimicrobial activity of nickel complexes. All nickel complexes have shown appreciable antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The SEM imaging studies were performed to know the mechanism of cell death, and results revealed that the cell wall inhibition is the main reason for bacterial cell death. The cytotoxicity of these complexes and their respective ligands for human cell lines was established with the HeLa cell, and observations affirm 85−90% cell viability after 24 h. KEYWORDS: Nickel complexes, Photophysical properties, Antibacterial, MRSA, Cytotoxicity and SEM studies

■

structural support.15−18 Bacteria are microscopic single-celled prokaryotic microorganisms, and the morphological features of bacteria vary from species to species; however, they are omnipresent.19−21 It is noteworthy that not all bacteria are harmful; some cause harmful effects on living organism. These bacteria are categorized as pathogenic bacteria. Bacterial infection is a key health challenge, causing a number of diseases in clinical settings and community environment.22−24 Antibiotics are the key choice for treatment of bacterial infection; however, the overuse of antibiotics leads to the adaptation of bacteria against antibiotics.25,26 It is imperative to introduce new antibacterial drugs from time to time to fight antibacterial infection. However, the major challenge involves discovery and development of new antimicrobial drug because of multistep synthesis, high cost, and potential side effects. Recently, coordination complexes have gained tremendous attention in the field of medicinal chemistry, because of interaction of metal complexes with bacterial cell membranes

INTRODUCTION Over the last few decades, the transition metal complexes found extensive application in biological science such as antimicrobial, antifungal, anti-inflammatory, and anticancer activities.1,2 Such activities of metal complexes are rapidly growing in the field of bioinorganic chemistry and help to improve the quality of the life.3 Metal and metalloid based drugs play significant role in the field of medicinal chemistry, e.g., Ehrlich et al. synthesized first metalloid based drug (organoaresnide) for successful treatment of syphilis.4 Cisplatin is another metal-based drug used for antitumor activities.5,6 Beside these drugs, several ruthenium complexes targeted for anticancer activities have entered into phase I clinical trial.7−9 The field is not limited to precious metal complexes; however, other transition metal complexes such as silver(I), gold(I), platinium(II), iron(III), copper(II/I), nickel(II), and titanium(II) were synthesized and tested for their biological activities.10−14 The chemical properties of these coordination complexes such as (1) Lewis acid character, (2) interaction with ligand, (3) partially filled d subshell, (4) redox activity, (5) charge, and (6) structure and bonding impart various functions in living systems such as oxygen transport, protein hydrolysis, DNA transcription, and © 2017 American Chemical Society

Received: March 30, 2017 Revised: June 1, 2017 Published: June 1, 2017 6070

DOI: 10.1021/acssuschemeng.7b00963 ACS Sustainable Chem. Eng. 2017, 5, 6070−6080

Research Article

ACS Sustainable Chemistry & Engineering Scheme 1. Structure of lLigands H2L1, H4L2, and L3−L5a

a

The potential cation binding sites of ligands are highlighted in red.

and other targets of the microorganism.27−29 These properties of metal complexes make them superior to the carbon-based compounds because of the synergic effect of both organic receptors and metal scaffolds.30 In the present manuscript, we have synthesized five imine-linked ligands and prepared their complexes with nickel ions. Furthermore, the isolated nickel complexes have been tested for antimicrobial activity against bacterial and fungal strains. The maximum effectiveness of all nickel complexes used was found against Gram-positive bacteria. The reason for bacterial cell death was confirmed by SEM imaging analysis, which shows that the inhibition of cell wall is the main cause of bacterial death. The choice of these complexes for antimicrobial activity was due to the synergized effect of both ligands and metal ions to inhibit the growth of microorganism. The rational design of the ligand, which contain disulfide and imine groups, has great effectiveness against antibacterial activity as reported in literature.31,32 The disulfide linkages are the important constituents of antimicrobial peptides and broadly found in natural plant and animals.33−35 The imine linkage is also present in some natural products and has been shown to have some broad biological activities include antifungal, antibacterial, antimalarial, antiproliferative, anti-inflammatory, and antiviral properties.32,36

489 (M + 1), 437 (M + 1), 427 (M + Na), 403 (M + 1), respectively. Synthesis and Characterization of Metal Complexes Ni2(L1)2, Ni(H2L2), Ni(L3)−Ni(L5). All the metal complexes were synthesized through the reaction of respective ligands H2L1, H4L2, and L3−L5 with the methanolic solution of nickel nitrate; upon completion of the reaction, the green color powder separated out and was washed with diethyl ether and dried under vacuum. The FTIR spectra of all the nickel complexes have shown significant shifts in the vibration frequency when compared with those of the pure ligands. All the nickel complexes display vibration frequency in the range of 1620−1660 cm−1 corresponding to the imine group, which is significantly shifted as compared to those of their respective ligands as shown in Figure S21−25. These shifts in imine linkage of all nickel complexes confirm the coordination of nitrogen donor site with the nickel ion. The absence of O−H vibration band in the range of 3200−3450 cm−1 in Ni2(L1)2 and Ni(H2L2) complexes confirms the coordination of O donor site with the nickel ion. The significant vibration shift in the C−S vibration band (700−500 cm−1) of all nickel complexes with respect to those of their ligands confirms the coordination of S donor site with the nickel ion. The mass spectra of all nickel complexes were obtained at 1226, 577, 636, 606, and 604 corresponding to dinuclear and mononuclear complexes. Photophysical Properties. The photophysical properties of all the five ligands H2L1, H4L2, and L3−L5 were recorded through UV−vis absorption and emission spectroscopy in DMSO as a solvent. H2L1 showed two broad absorption bands (λabs) at 322 and 405 nm, respectively, due to π → π* transition of the conjugated system in the ligand (Figure S28A).38 Similarly, H4L2 displayed an absorption band at 325 nm and a shoulder at 375 nm which was most likely again due to π → π* transition (Figure S28B).38,39 L3 shows three broad absorption bands at 275, 320, and 375 nm and were attributed to n → π* and π → π* transitions (Figure S28C). Similarly, L4 displays three broad absorption bands at 275, 310, and 360 nm corresponding to n → π* and π → π* transitions (Figure S28D). L5 shows two absorption bands, one at 270 nm corresponding to n → π* and a second broad absorption band in the range of 280−400 nm corresponding to π → π*

■

RESULT AND DISCUSSION Syntheses and Characterization of Ligands H2L1, H4L2, and L3−L5. Ligand H2L1 and H4L2 were synthesized through a previously reported procedure,37 and ligand L3 was synthesized through a condensation reaction between 2,2′disulfanediyldianiline and thiophene-2-carboxaldehyde in ethanol. A procedure was adopted to synthesize ligands L4 and L5 similar to that used for the synthesis of L3. H2L1, H4L2, and L3−L5 (Scheme 1) were fully characterized through NMR, FTIR, and mass spectrometry as shown in Figures S1−S20. 1H NMR spectra revealed the formation of imine linkage in all ligands H2L1, H4L2, and L3−L5 as exhibited with signal at 8.23−9.73 ppm, and 13C NMR exhibits signal at 165−149 ppm. The FTIR spectra of H2 L1, H 4L2, and L3−L5 have characteristic imine linkage bands within 1590−1630 cm−1. ESI-mass spectra of H2L1, H4L2, and L3−L5 are presented in Figures S15−S20. The experimental molecular ion peaks for H2L1, H4L2, and L3−L5 were obtained at (m/z) 557 (M + 1), 6071


Research Article

ACS Sustainable Chemistry & Engineering

Figure 1. Change in the UV−vis absorption spectra on addition of 0−20 μM Ni2+ to the DMSO solution (10 μM) of (A) H2L1, (B) H4L2, (C) L3, (D) L4, and (E) L5. (F) Photographic images of all the ligands and their nickel complexes.

transition (Figure S28E).39,40 The binding of H2L1, H4L2, and L3−L5 with the pool of metal ions (such as Fe3+, Cu2+, Zn2+, Co3+, Mn2+, Cr2+, Na+, K+, and Ni2+) demonstrate the most significant binding with Ni2+ as observed from the modulation of absorption spectrum. The absorption profile (λabs) for H2L1 (10 μM) in DMSO was shifted from 322 to 342 nm and from 405 to 470 nm on addition of 20 μM Ni2+ ions. The significant change in absorption profile of H2L1 on addition of nickel ion

clearly demonstrates the interaction with the Ni2+ ions (Figure S28A) and further confirms the binding of Ni2+ within the coordination sphere of H2L1 the titration experiment was performed. In titration experiment, 0−20 μM Ni2+ was added to a fixed concentration of H2L1 (10 μM) in DMSO, and absorption profile was recorded after addition of each. Addition of successive amounts of Ni2+ to H2L1 led to the increase in the absorbance at 342 and 470 nm with two isosbestic points at 350 6072


Research Article

ACS Sustainable Chemistry & Engineering Table 1. Photophysical Parameter of Ligands and Metal Complexes no.

Ligand/metal complex

1 2 3 4 5 6 7 8 9 10

H2L1 H4L2 L3 L4 L5 Ni2(L1)2 Ni(H2L2) Ni(L3) Ni(L4) Ni(L5)

λabs (nm) 322, 325, 275, 275, 275, 470 450 425 425 425

405 375 320, 360 310, 360 350

ε0 (L mol−1 cm−1) 65000, 35000, 18000, 30000, 18000, 40000 7500 17000 25000 25000

60000 25000 22000, 12000 40000, 25000 20000

absorption transition π− π− n− n− n− 3 A2g 3 A2g 3 A2g 3 A2g 3 A2g

π* π* π*, π − π* π*, π − π* π*, π − π* (F) → 3T1g (F) → 3T1g (F) → 3T1g (F) → 3T1g (F) → 3T1g

(P) (P) (P) (P) (P)

λem (nm)

quantum yield (Φs)

525 450 430 420 415 525 450 430 420 415

0.84 0.45 0.55 0.57 0.55 0.25 0.10 0.12 0.22 0.13

in the coordination environment of the ligand. To further investigate the effect of Ni2+ on emission profile of H2L1, titration experiment was performed. In titration experiment, 0− 20 μM Ni2+ was added to 10 μM H2L1 solution, and subsequent quenching in the emission profile was observed as shown in Figure 2A. The quenching in fluorescence intensity was due to the open shell of the metal ions.44 The nickel ions are paramagnetic in nature. The reduction potential of nickel lies between the HOMO−LUMO gap of the ligand; as a result, the excited state energy of ligand transfer to unpaired d orbital of the nickel. Therefore, the quenching in the fluorescence intensity of the ligand was takes place. It is already reported in literature that the paramagnetic metal ions such as Cu2+, Pb2+, Hg2+, Cd2+, and Ni2+ show quenching in the fluorescence spectra due to energy or charge transfer process.45,46 Similarly, ligand H4L2 was excited at (λex) = 375 nm, demonstrating emission at 450 nm; however, when 20 μM Ni2+ was added to this solution, 12-fold quenching in the emission profile was observed. Furthermore, on addition of 0−20 μM Ni2+ to 10 μM H4L2, the subsequent quenching in emission profile was observed as shown in Figure 2B. The reason for quenching was same as that observed for H2L1. Ligands L3−L5 were excited at (λex) 375, 360, and 375 nm and exhibited photoluminescence at (λem) 430, 420, and 415 nm, respectively. On addition of 0−20 μM Ni2+ to 10 μM L3, 25-fold quenching was observed in the emission spectrum of ligand as in Figure 2C. Similarly, on adding 0−20 μM Ni2+ to L4 and L5, 2- and 10-fold quenching was observed in the emission profile as in Figure 2D,E. These results clearly indicate the nickel coordinate in the coordination sphere of the ligands. The calibration plots of all complexes were obtained by plotting fluorescence intensity versus nickel concentration (20 μM) as shown in Figure 2F. The calibration plot revealed that fluorescence intensity linearly decreased with increased concentration of nickel ion. To further determine the stoichiometry of ligands H2L1, H4L2, and L3−L5 with Ni2+ ions, Job’s plot analysis has been performed.47 It was concluded from the Job’s plot analysis that ligands H2L1, H4L2, and L3−L5 showed 1:1 stoichiometry with the nickel ion (Figure S29A−E). The stoichiometry between ligand and nickel ion established from the Job’s analysis were fully supported by mass results. The number of species distribution in solution and the binding constant for all ligands with nickel ion is also studied with hyperspec software.48,49 The hyperspec result shows that 1:1 species is dominant in the solution which is also in agreement with the Job’s result. The binding constants (Ka) of all ligands for Ni2+ ions were determined by using Benesi Hildebrand equation: 1/[I − I0] versus 1/[Ni2+], whereas I is the fluorescence intensity of ligands in the presence of Ni2+ and I0 is the fluorescence

and 425 nm. The new absorbance band arising at 470 nm was due to d−d transition of nickel complex as shown in Figure1A. Similarly the H4L2 was check with the same metal ions as used for H2L1, the most significant change in absorbance was observed with Ni2+ as shown in Figure S28B. Titration experiment was performed to confirm the reproducibility of the binding of Ni2+ ion with H4L2.In titration experiment, on addition of aliquot amount of Ni2+ to H4L2 solution led to increase in the intensity of the absorbance band at 450 nm with one isosbestic point at 340 nm. The absorbance band at 450 nm corresponds to d-d transition of the nickel complex as shown in Figure 1B.41 Similarly, L3−L5 were treated with same library of metal ions as used for ligands H2L1 and H4L2; however, the most significant change in absorbance was observed with Ni2+ as shown in Figure S28C−E. In all three ligands, a new broad absorption band arises at 425 nm which corresponds to d−d transition of the nickel complex.41 This clearly shows the binding of Ni2+ with the coordination sphere of all three ligands L3−L5. Furthermore, titration experiment was performed to confirm the binding of Ni2+ ion with L3−L5. In titration experiment, 0−20 μM Ni2+ was added to the ligands solution, and absorbance was recorded as shown in Figure 1C− E. It was determined from the graph that the absorbance intensity increases at 425 nm on subsequent addition of Ni2+ to ligands solution. These UV−vis absorption studies inspired us to prepare the Ni complexes of these ligands and highlight the binding site in the coordination sphere of the ligands. The electronic absorption spectra of all five nickel complexes was observed in DMSO, complex Ni2(L1)2 shows a broad absorption band (λabs) with maxima 470 nm (ε0 = 40 000 L mol−1 cm−1) corresponding to spin-allowed transition of 3A2g (F) →3T1g (P), highlighting the distorted octahedral geometry of the complex. Similarly, Ni(H2L2) complex show a broad absorption band (λabs) with maxima 450 nm (ε0 = 7500 L mol−1 cm−1) corresponding to spin-allowed transition of 3A2g (F) → 3T1g (P), which again highlights the distorted octahedral geometry. Complexes Ni(L3), Ni(L4), and Ni(L5) display a broad absorption band (λabs) with maxima 425 nm (ε0 = 17 000, 25 000, and 25 000 L mol−1 cm−1) which was attributed to spin-allowed transition of 3A2g(F) → 3T1g (P) and emphasizes the octahedral geometry as shown in Table 1.42,43 The emission profiles of all five ligands were studied in DMSO, and the Ni2+ binding with the coordination sphere were observed through emission profile. Ligand H2L1 (10 μM) was excited at (λex) = 405 nm, and it exhibited photoluminescence at (λem) = 525 nm, whereas on addition of 20 μM Ni2+ ion the photoluminescence properties of H2L1 quenches about 5.5-fold. The significant change in the emission intensity of H2L1 on addition of Ni2+ signifies the coordination of nickel 6073


Research Article


Figure 2. Change in the emission spectra on addition of 0−20 μM Ni2+ to the DMSO solution (10 μM) (A) H2L1, (B) H4L2, (C) L3, (D) L4, and (E) L5. (F) Calibration plot of all the ligands with respect to the Ni2+ ions.

intensity of pure ligand (Figure S29F).50 The binding constants of ligands H2L1, H4L2, and L3−L5 for Ni2+ (Ka) were 5.71 × 104, 1.16 × 104, 7.1 × 103, 6.4 × 103, 6.3 × 103, respectively. Electrochemistry. The redox behavior of all nickel complexes were measured in DMSO in the potential range of +1.0 to −1.0 V and the electrochemical data summarized in the Table S1. All the nickel complexes have shown one quasireversible reduction peak in the range of −0.85 to −0.50 V.51,52 The Ni2(L1)2 complex shows a cathodic peak (Epc) at −0.75 V

and an anodic peak (Epa) at −0.53 V as shown in Figures S31A. The other nickel complexes, Ni(H2L2), Ni(L3), Ni(L4), and Ni(L5), display cathodic peaks at −0.72, −0.81, −0.79, and −0.76 V and anodic peaks at −0.56, −059, −0.52, and −0.50 V, respectively (Figure S31B−E). The redox potential of all nickel complexes among negative was due to the presence of conjugated aromatic ring. The coulmeteric experiment was performed to confirm the number of electron transfer in redox process. The potentiometric exhaustive electrolysis performed at −100 mV negative to the reduction peak and shows that the 6074


Research Article

ACS Sustainable Chemistry & Engineering Table 2. In Vitro Antibacterial Activity of the Nickel Complexes MIC (μg mL−1) no.

sample

1 2 3 4 5 6 7 8 9 10 11 12

H2L1 H4L2 L3 L4 L5 Ni2(L1)2 Ni(H2L2) Ni(L3) Ni(L4) Ni(L5) Ciprofloxacin Ni(NO3)2·6H2O

S. aureus (MTCC-740) 80 83 98 91 92 14 18 26 29 30 10 60

± ± ± ± ± ± ± ± ± ± ± ±

P. aeruginosa (MTCC-741)

2 2.5 2 2 3 2 1 2 2 3 2 3

300 290 301 305 300 100 153 130 150 200 7 75

± ± ± ± ± ± ± ± ± ± ± ±

2 2 2 2 2 2 2 3 2 3 2 2

S. flexneri (MTCC-1457) 350 310 290 300 295 200 200 300 270 250 17 59

± ± ± ± ± ± ± ± ± ± ± ±

E. coli (MTCC-119)

2 2 2 2 2 1 2 1 1.5 1 2 3

100 95 110 119 120 73 77 81 74 91 21 56

± ± ± ± ± ± ± ± ± ± ± ±

MRSA

2 2 2 2 2 0.5 1 1 0.5 1 2 2

140 181 179 197 194 20 30 41 47 48 − 70

± ± ± ± ± ± ± ± ± ±

2 2 2 2 2 2 2 2 2 1

±3

Table 3. In Vitro Antifungal Activity of all Nickel Complexes MIC (μg/mL−1) no.

sample

1 2 3 4 5 6 7 8 9 10 11

H2L1 H4L2 L3 L4 L5 Ni2(L1)2 Ni(H2L2) Ni(L3) Ni(L4) Ni(L5) Fluconazole

A. niger (MTCC-281) 400 410 420 413 411 100 150 155 180 200 50

± ± ± ± ± ± ± ± ± ± ±

2 2 2 2 2 0.5 1 0.5 1 1 2

C. candidum (MTCC-3993) 500 505 510 520 510 201 203 209 210 280 32

± ± ± ± ± ± ± ± ± ± ±

2 2 2 2 2 2 2 2 2 2 2

C. albicans (MTCC-227) 289 317 431 371 301 150 189 230 250 212 34

± ± ± ± ± ± ± ± ± ± ±

2 2 2 2 2 1 1 1 2 1 2

C. tropicalis (MTCC-230) 150 133 200 155 130 110 103 150 189 120 20

± ± ± ± ± ± ± ± ± ± ±

2 2 2 2 2 1 1 2 3 1 2

ment is a big challenge to healthcare departments because of multiple mechanisms for antibacterial resistance.57,58 Thus, it is imperative to examine the antimicrobial activity of newly synthesized materials and investigate their effectiveness. Here, we have synthesized five imine-linked ligands H2L1, H4L2, and L3−L5, prepared their complexes with nickel ions complexes, and investigated their antimicrobial activity. Pure ligands H2L1, H4L2, and L3−L5 and their nickel complexes Ni2(L1)2− Ni(L5) were screened for antibacterial activities via broad dilution method and in vitro antimicrobial activity against S. aureus (MTCC-740), methicillin resistant S. aureus (MRSA), Shigella flexneri (MTCC-1457), P. aeruginosa (MTCC-741), Escherichia coli (MTCC-119), Aspergillus niger (MTCC-281), Candidum candidum (MTCC-3993), Candidum albicans (MTCC-227), and Candidum tropicalis (MTCC-230). The disc diffusion method was also used to determine the activity of all ligands and their nickel complexes against tested bacteria. The results of disc diffusion method show that some of nickel complexes are active against different strain of treated bacteria. Furthermore, minimum inhibitory concentration (MIC) value was determined through turbidity method, and the MIC values against tested bacteria are shown in Table 2. Ciprofloxacin is taken as standard reference drug and tested with conditions similar to those used for pure ligands and nickel complexes. The solvent DMSO has no effect on the antibacterial activity of tested bacteria. All the pure ligands exhibited moderate antibacterial activity with respect to that of the reference drug for the aforementioned bacteria. The pure nickel nitrate (20 μM) solution is also tested for antibacterial activity against the referenced bacteria. It was concluded from the MIC value that

consumption of one electron takes place per complex (n = 0.92−0.94).53 The one-electron quasi-reversible reduction of all the complexes is attributed to NiII/NiI redox couple.37 To further corroborate the quasi-reversible nature of the redox reaction, the scan rate experiment was performed from 50−300 mV s−1 as shown in Figure S31A−E. The result demonstrates that the value of ΔEp is more than 0.59/n mV and increases with scan rate. The ratio of (Ipc/Ipa) cathodic peak current to anodic peak current is also greater than 1. These examinations strongly confirm that the redox reactions are quasi-reversible in nature.54 In the positive potential, complexes Ni2(L1)2 and Ni(H2L2) show one-electron quasi-reversible oxidation peak in the range of 0.68−0.10 V, attributed to NiII/NiIII. Further scan rate experiments confirm the quasi-reversible oxidation process. The redox behavior of all the ligands were studied in DMSO in the potential range of +1.0 to −1.0 V and [nBu4N][ClO4] as supporting electrolyte. It was concluded from the graph that all ligands had different electrochemical behavior compared to that of their respect complexes as shown in Figure S31F. Antibacterial Activity. The assessment of new materials as antimicrobial drugs is of immense interest because of the prevailed multidrug resistance in widespread pathogen and hence progression of new infection.55 A recent report published by Tenover et al. confirmed that the Staphylococcus aureus and Pseudomonas aeruginosa are the prominent species identified for pathogen of many disease.56 For fungal infection, the Candidum species are the most common fungi which cause candidiasis infection in human. Candidum albicans is responsible for morbidity and mortality in immunocompromised patients. The control of spreading of these microorganisms in the environ6075


Research Article


Figure 3. SEM images of S. aureus at different incubation time: (A) S. aureus cell before treatment of nickel complexes, (B) Immediate after treatment of nickel complexes, (C) 4 h of incubation after treatment, (D) 8 h of incubation after treatment.

Figure 4. (A) and (B) Time kill assay of complex Ni2(L1)2, Ni(H2L2), and Ni(L3)−Ni(L5) against S. aureus.

Ni(NO3)2·6H2O lethality to bacteria is less than that of the reference drug but more than that of the free ligands. All metal complexes Ni2(L1)2−Ni(L5) exhibited very good antibacterial activity against S. aureus (MIC = 15−40 μg/mL−1) and methicillin resistant S. aureus (MRSA) (MIC = 20−50 μg/ mL−1) with respect to that of Ciprofloxacin, while in the case of Gram-negative bacteria, their activities were found to be moderate as determined from their MIC value. Thus, it was concluded that the free ligand and metal solution independently show moderate activity; however, in complex formation, their antimicrobial activities against S. aureus (MTCC-740) and MRSA were enhanced several fold. The reason for the antimicrobial activity of complex might be high toxicity at cell surface, structural specificity, and high redox potential (as confirmed from redox properties) which can damage the biomolecules within the cell or cell surface. This confirms the synergized effect of both ligand and Ni2+ ion for inhibition the growth of microorganism. The antifungal activity of all nickel complexes and pure ligands were evaluated against fungal strains such as C. tropicalis (MTCC-230), C. albicans (MTCC-227), C. candidum (MTCC3993), and A. niger (MTCC-281). The MIC value was

determined through turbidity method. Fluconazole is taken as a reference drug, studied under conditions similar to those for all ligands and their nickel complexes. It was concluded from the MIC value that all nickel complexes and their pure ligands exhibited moderate antifungal activity on tested fungal strains as compared to that of reference drug as shown in Table 3. Mechanism of Action. In existing literature, the possible reasons for bacterial cell death through metal complexes included cell wall synthesis inhibition, cell membrane disruption, nucleic acid synthesis inhibition, and protein synthesis inhibition.59 The bacterial cell membrane is made up of anionic polymer which provides the coordinated site for cationic metal complexes.60 The interaction of these metal complexes with cell membrane disrupts normal physiological and chemical functions which are important for survival of the bacterial cell. Metal ions act as a catalyst for oxidation of specific peptide side chain and inhibit the cellular activity of the healthy bacterial cell. The tunable redox properties of metal complexes generate reactive oxygen species and hydrolysis of phosphoester bond, damage the DNA, and prevent meticulous enzyme activity which is significant for cell growth.61,62 The inhibition of cell wall synthesis to induce bacterial death is the 6076


Research Article


Figure 5. MTT assay of cell viability percentage of HeLa cell after incubation for 24 h: (A) for each complex and (B) for all ligands. Viability was considered 100% in case of control without any complex added to it.

Cell Viability Assay. The cytotoxicity to human cells is one factor which is very important when dealing with biological activity. The cytotoxicity of nickel complexes was evaluated using MTT assay with HeLa cells cultured in growth medium. The HeLa cells were incubated at 37 °C for 24 h in 5% carbon dioxide environment. The nickel complexes (25 μM) and those of their respective ligands (30 μM) were incubated with cells at 37 °C for 24 h. After 24 h, we observed 90−96% cell viability in the case of nickel complexes as in Figure 5A and 85−90 % in the case of ligands. Furthermore, to check cell viability at higher concentration, dose-dependent studies were carried out. The results of dose-dependent studies revealed that 80−85% of HeLa cells survived in the concentration range of 120−160 μM in the case of both nickel complexes (Figure 5B) and their respective ligands.

most common mode of action of antibacterials. The bacterial cell wall is made up of peptidoglycan and inhibited at early stages of cell growth. In the literature, various reports are available which propose the mechanism of bacterial death by cell wall rupturing, for example, Kaur et al. found cell death of bacteria could occur by rupturing of cell via silver and gold nanoparticle.63 Mohamed et al. found bacterial cell death with imine-linked metal complexes due to cell lysis.64 Zuo and coworkers synthesized surface-bound silver ion for breakage of the cell wall of S. aureus.65 Thus, it is concluded from the above report that DNA binding, cell rupturing, and protein binding are the responsible factors for growth inhibition of the bacteria. To understand the antibacterial effect of all prepared nickel complexes, the changes in morphology and membrane integrity of S. aureus cells due to interaction with complexes were evaluated by SEM images as shown in Figure 3. As depicted by SEM images of bacterial S. aureus cell, the morphology of cell show regular spherical shape and cell membrane remain intact when cultured in the absence of nickel complexes as shown in Figure 3A. Furthermore, the S. aureus cell images were observed with different intervals of incubation time after addition of nickel complexes. The SEM result shows that bacterial cell starts disintegrate through “bleb” formation as shown in Figure 3B,C. After 8 h of treatment with the nickel complex, complete cell membrane disintegration occurred in bacterial cells, and cytoplasm is blown outside the cell as shown in Figure 3D. Thus, it is concluded that the nickel complex causes the bacterial death through cell membrane disruption. Time Kill Assay. This assay was performed by viable cell count method. The time killing studies not only give the information about the nature of microbial agent (bactericidal or bacteriostatic) but also revealed the complete killing of specific microorganism. This studies revealed that the Ni2(L1)2 complex showed 80% killing of S. aureus within 4 h of the incubation. The complete killing of S. aureus occurs within 8 h of incubation as shown in Figure 4A. The other nickel complexes such as Ni(H2L2) and Ni(L3)−Ni(L5) showed complete killing of S. aureus cell within 10−12 h of the incubation as shown in Figure 4B. The difference in killing effects of complex Ni2(L1)2 versus those of other complexes Ni(H2L2) and Ni(L3)−Ni(L5) was due to the presence of extra phenyl ring and excess of nickel which cause toxicity to the cell.66,67

■

CONCLUSION We have synthesized five nickel complexes of ligands, H2L1, H4L2, and L3−L5, and characterized through spectroscopic data. The Job’s plot analysis demonstrates that Ni2+ forms 1:1 complexes with ligands H2L1, H4L2, and L3−L5. The ESI-mass and FTIR spectroscopy data confirm the coordination site and geometry of the all complexes. Furthermore, these nickel complexes were explored as antimicrobial agents against Grampositive and -negative bacteria and different fungal strains. All complexes show maximum antibacterial activity against S. aureus and methicillin resistant S. aureus as evident from their MIC values with respect to those of Ciprofloxacin. Against some Gram-negative bacteria such as S. flexneri MTCC-1457, P. aeruginosa MTCC-741, and E. coli MTCC-119 they were found to have some moderate activity. Cell wall inhibition is main reason for bacterial cell death as evident from the SEM studies. These nickel complexes were also tested against different strains of fungi, and we observed that the moderate activity was found with respect to that of Fluconazole. Nontoxicity of these nickel complexes and respective ligands were studied on HeLa cells, and we found 85−90% cell viability after 24 h.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssuschemeng.7b00963. 6077


Research Article


■

(14) Wojciechowska, A.; Daszkiewicz, M.; Staszak, Z.; Trusz-Zdybek, A.; Bień k o, A.; Ozarowski, A. Synthesis, Crystal Structure, Spectroscopic, Magnetic, Theoretical, and Microbiological Studies of a Nickel(II) Complex of l-Tyrosine and Imidazole, [Ni(Im)2(l-tyr)2]· 4H2O. Inorg. Chem. 2011, 50 (22), 11532−11542. (15) Krishnamoorthy, P.; Sathyadevi, P.; Muthiah, P. T.; Dharmaraj, N. Nickel and cobalt complexes of benzoic acid (2-hydroxybenzylidene)-hydrazide ligand: synthesis, structure and comparative in vitro evaluations of biological perspectives. RSC Adv. 2012, 2 (32), 12190−12203. (16) Szaciłowski, K.; Macyk, W.; Drzewiecka-Matuszek, A.; Brindell, M.; Stochel, G. Bioinorganic Photochemistry: Frontiers and Mechanisms. Chem. Rev. 2005, 105 (6), 2647−2694. (17) Kepp, K. P. Bioinorganic Chemistry of Alzheimer’s Disease. Chem. Rev. 2012, 112 (10), 5193−5239. (18) Denny, J. A.; Darensbourg, M. Y. Metallodithiolates as Ligands in Coordination, Bioinorganic, and Organometallic Chemistry. Chem. Rev. 2015, 115 (11), 5248−5273. (19) Chung, H. J.; Reiner, T.; Budin, G.; Min, C.; Liong, M.; Issadore, D.; Lee, H.; Weissleder, R. Ubiquitous Detection of GramPositive Bacteria with Bioorthogonal Magnetofluorescent Nanoparticles. ACS Nano 2011, 5 (11), 8834−8841. (20) Epand, R. M.; Epand, R. F. Domains in bacterial membranes and the action of antimicrobial agents. Mol. BioSyst. 2009, 5 (6), 580− 587. (21) Zhou, J.; Qi, G.-B.; Wang, H. A purpurin-peptide derivative for selective killing of Gram-positive bacteria via insertion into cell membrane. J. Mater. Chem. B 2016, 4 (28), 4855−4861. (22) Batalha, P. N.; Gomes, A. T. P. C.; Forezi, L. S. M.; Costa, L.; de Souza, M. C. B. V; Boechat, F.; da, C. S.; Ferreira, V. F.; Almeida, A.; Faustino, M. A. F.; Neves, M. G. P. M. S.; et al. Synthesis of new porphyrin/4-quinolone conjugates and evaluation of their efficiency in the photoinactivation of Staphylococcus aureus. RSC Adv. 2015, 5 (87), 71228−71239. (23) Wang, X.; Wolfbeis, O. S. Fiber-Optic Chemical Sensors and Biosensors. Anal. Chem. 2013, 85 (2), 487−508. (24) Zhao, Y.; Tian, Y.; Cui, Y.; Liu, W.; Ma, W.; Jiang, X. Small Molecule-Capped Gold Nanoparticles as Potent Antibacterial Agents That Target Gram-Negative Bacteria. J. Am. Chem. Soc. 2010, 132 (35), 12349−12356. (25) Mingeot-Leclercq, M.-P.; Decout, J.-L. Bacterial lipid membranes as promising targets to fight antimicrobial resistance, molecular foundations and illustration through the renewal of aminoglycoside antibiotics and emergence of amphiphilic aminoglycosides. MedChemComm 2016, 7 (4), 586−611. (26) Chen, J.; Wang, F.; Liu, Q.; Du, J. Antibacterial polymeric nanostructures for biomedical applications. Chem. Commun. 2014, 50 (93), 14482−14493. (27) Lemire, J. A.; Harrison, J. J.; Turner, R. J. Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat. Rev. Microbiol. 2013, 11 (6), 371−384. (28) Haas, K. L.; Franz, K. J. Application of Metal Coordination Chemistry To Explore and Manipulate Cell Biology. Chem. Rev. 2009, 109 (10), 4921−4960. (29) Ma, Z.; Jacobsen, F. E.; Giedroc, D. P. Coordination Chemistry of Bacterial Metal Transport and Sensing. Chem. Rev. 2009, 109 (10), 4644−4681. (30) Pandrala, M.; Li, F.; Feterl, M.; Mulyana, Y.; Warner, J. M.; Wallace, L.; Keene, F. R.; Collins, J. G. Chlorido-containing ruthenium(ii) and iridium(iii) complexes as antimicrobial agents. Dalt. Trans 2013, 42 (13), 4686−4694. (31) Wanniarachchi, Y. A.; Kaczmarek, P.; Wan, A.; Nolan, E. M. Human Defensin 5 Disulfide Array Mutants: Disulfide Bond Deletion Attenuates Antibacterial Activity against Staphylococcus aureus. Biochemistry 2011, 50 (37), 8005−8017. (32) da Silva, C. M.; da Silva, D. L.; Modolo, L. V.; Alves, R. B.; de Resende, M. A.; Martins, C. V. B.; de Fátima, Â . Schiff bases: A short review of their antimicrobial activities. J. Adv. Res. 2011, 2 (1), 1−8.

Experimental details; NMR, mass, FTIR, and UV−visible spectra (PDF) Single crystal data for L3 (CIF) Single crystal data for L4 (CIF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Tel.: +91-1881242176. ORCID

Narinder Singh: 0000-0002-8794-8157 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was supported with research grant from DST India [Project No. EMR/2014/000613]. P.R. and A.S. are thankful to UGC (New Delhi) and CSIR - New Delhi India for Senior Research fellowship.

■

REFERENCES

(1) Psomas, G.; Kessissoglou, D. P. Quinolones and non-steroidal anti-inflammatory drugs interacting with copper(II), nickel(II), cobalt(II) and zinc(II): structural features, biological evaluation and perspectives. Dalt. Trans. 2013, 42 (18), 6252−6276. (2) Li, F.; Collins, J. G.; Keene, F. R. Ruthenium complexes as antimicrobial agents. Chem. Soc. Rev. 2015, 44 (8), 2529−2542. (3) Gaynor, D.; Griffith, D. M. The prevalence of metal-based drugs as therapeutic or diagnostic agents: beyond platinum. Dalt. Trans. 2012, 41 (43), 13239−13257. (4) Aminov, R. I. A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future. Front. Microbiol. 2010, 1, 134. (5) Wong, E.; Giandomenico, C. M. Current Status of PlatinumBased Antitumor Drugs. Chem. Rev. 1999, 99 (9), 2451−2466. (6) Muhammad, N.; Guo, Z. Metal-based anticancer chemotherapeutic agents. Curr. Opin. Chem. Biol. 2014, 19, 144−153. (7) Gorle, A. K.; Feterl, M.; Warner, J. M.; Wallace, L.; Keene, F. R.; Collins, J. G. Tri- and tetra-nuclear polypyridyl ruthenium(II) complexes as antimicrobial agents. Dalt. Trans. 2014, 43 (44), 16713−16725. (8) Li, X.; Heimann, K.; Li, F.; Warner, J. M.; Richard Keene, F.; Grant Collins, J. Dinuclear ruthenium(II) complexes containing one inert metal centre and one coordinatively-labile metal centre: syntheses and biological activities. Dalt. Trans. 2016, 45 (9), 4017− 4029. (9) Komor, A. C.; Barton, J. K. The path for metal complexes to a DNA target. Chem. Commun. 2013, 49 (35), 3617−3630. (10) Wanninger, S.; Lorenz, V.; Subhan, A.; Edelmann, F. T. Metal complexes of curcumin - synthetic strategies, structures and medicinal applications. Chem. Soc. Rev. 2015, 44 (15), 4986−5002. (11) Papanikolaou, P. A.; Papadopoulos, A. G.; Andreadou, E. G.; Hatzidimitriou, A.; Cox, P. J.; Pantazaki, A. A.; Aslanidis, P. The structural and electronic impact on the photophysical and biological properties of a series of CuI and AgI complexes with triphenylphosphine and pyrimidine-type thiones. New J. Chem. 2015, 39 (6), 4830− 4844. (12) Jaros, S. W.; Guedes da Silva, M. F. C.; Król, J.; Conceiçaõ Oliveira, M.; Smoleński, P.; Pombeiro, A. J. L.; Kirillov, A. M. Bioactive Silver−Organic Networks Assembled from 1,3,5-Triaza-7-phosphaadamantane and Flexible Cyclohexanecarboxylate Blocks. Inorg. Chem. 2016, 55 (4), 1486−1496. (13) Jaros, S. W.; Guedes da Silva, M. F. C.; Florek, M.; Smoleński, P.; Pombeiro, A. J. L.; Kirillov, A. M. Silver(I) 1,3,5-Triaza-7phosphaadamantane Coordination Polymers Driven by Substituted Glutarate and Malonate Building Blocks: Self-Assembly Synthesis, Structural Features, and Antimicrobial Properties. Inorg. Chem. 2016, 55 (12), 5886−5894. 6078


Research Article

ACS Sustainable Chemistry & Engineering (33) Wu, Z.; Hoover, D. M.; Yang, D.; Boulegue, C.; Santamaria, F.; Oppenheim, J. J.; Lubkowski, J.; Lu, W. Engineering Disulfide Bridges to Dissect Antimicrobial and Chemotactic Activities of Human β -Defensin 3. Proc. Natl. Acad. Sci. U. S. A. 2003, 100 (15), 8880−8885. (34) Mnayer, D.; Fabiano-Tixier, A. S.; Petitcolas, E.; Hamieh, T.; Nehme, N.; Ferrant, C.; Fernandez, X.; Chemat, F. Chemical composition, antibacterial and antioxidant activities of six essentials oils from the Alliaceae family. Molecules 2014, 19 (12), 20034−20053. (35) Singh, M.; Singh, S. K.; Gangwar, M.; Nath, G.; Singh, S. K. Design, synthesis and mode of action of novel 2-(4-aminophenyl)benzothiazole derivatives bearing semicarbazone and thiosemicarbazone moiety as potent antimicrobial agents. Med. Chem. Res. 2016, 25 (2), 263−282. (36) Panneerselvam, P.; Nair, R. R.; Vijayalakshmi, G.; Subramanian, E. H.; Sridhar, S. K. Synthesis of Schiff bases of 4-(4-aminophenyl)morpholine as potential antimicrobial agents. Eur. J. Med. Chem. 2005, 40 (2), 225−229. (37) Raj, P.; Singh, A.; Kaur, K.; Aree, T.; Singh, A.; Singh, N. Fluorescent Chemosensors for Selective and Sensitive Detection of Phosmet/Chlorpyrifos with Octahedral Ni2+ Complexes. Inorg. Chem. 2016, 55, 4874−4883. (38) Cheng, J.; Wei, K.; Ma, X.; Zhou, X.; Xiang, H. Synthesis and Photophysical Properties of Colorful Salen-Type Schiff Bases. J. Phys. Chem. C 2013, 117 (32), 16552−16563. (39) Gou, C.; Qin, S. H.; Wu, H. Q.; Wang, Y.; Luo, J.; Liu, X. Y. A highly selective chemosensor for Cu2+ and Al3+ in two different ways based on Salicylaldehyde Schiff. Inorg. Chem. Commun. 2011, 14 (10), 1622−1625. (40) Boonkitpatarakul, K.; Wang, J.; Niamnont, N.; Liu, B.; Mcdonald, L.; Pang, Y.; Sukwattanasinitt, M. Novel Turn-On Fluorescent Sensors with Mega Stokes Shifts for Dual Detection of Al 3+ and Zn 2+. ACS Sensors 2016, 1 (2), 144−150. (41) Moroz, Y. S.; Kulon, K.; Haukka, M.; Gumienna-Kontecka, E.; Kozłowski, H.; Meyer, F.; Fritsky, I. O. Synthesis and Structure of [ 2 × 2 ] Molecular Grid Copper (II) and Nickel (II) Complexes with a New Polydentate Oxime-Containing Schiff Base Ligand. Inorg. Chem. 2008, 47 (13), 5656−5665. (42) Jesson, J. P.; Trofimenko, S.; Eaton, D. R. Spectra and structure of some transition metal poly(1-pyrazolyl) borates. J. Am. Chem. Soc. 1967, 89 (13), 3148−3158. (43) Kawamoto, T.; Nishiwaki, M.; Tsunekawa, Y.; Nozaki, K.; Konno, T. Synthesis and Characterization of Luminescent Zinc (II) and Cadmium (II) Complexes with N, S-Chelating Schiff Base Ligands. Inorg. Chem. 2008, 47 (8), 3095−3104. (44) Sharma, H.; Kaur, N.; Singh, A.; Kuwar, A.; Singh, N. Optical chemosensors for water sample analysis. J. Mater. Chem. C 2016, 4 (23), 5154−5194. (45) Anbu, S.; Ravishankaran, R.; Guedes da Silva, M. F. C.; Karande, A. A.; Pombeiro, A. J. L. Differentially Selective Chemosensor with Fluorescence Off−On Responses on Cu2+ and Zn2+ Ions in Aqueous Media and Applications in Pyrophosphate Sensing, Live Cell Imaging, and Cytotoxicity. Inorg. Chem. 2014, 53 (13), 6655−6664. (46) Jung, H. S.; Kwon, P. S.; Lee, J. W.; Kim, J.; Hong, C. S.; Kim, J. W.; Yan, S.; Lee, J. Y.; Lee, J. H.; Joo, T.; et al. Coumarin-Derived Cu2+-Selective Fluorescence Sensor: Synthesis, Mechanisms, and Applications in Living Cells. J. Am. Chem. Soc. 2009, 131 (5), 2008−2012. (47) Singh, A.; Singh, A.; Singh, N.; Jang, D. O. A benzimidazoliumbased organic trication: a selective fluorescent sensor for detecting cysteine in water. RSC Adv. 2015, 5 (88), 72084−72089. (48) Gans, P.; Sabatini, A.; Vacca, A. Investigation of equilibria in solution. Determination of equilibrium constants with the {HYPERQUAD} suite of programs. Talanta 1996, 43 (10), 1739−1753. (49) Ansari, S. A.; Yang, Y.; Zhang, Z.; Gagnon, K. J.; Teat, S. J.; Luo, S.; Rao, L. Complexation of Lanthanides with Glutaroimide-dioxime: Binding Strength and Coordination Modes. Inorg. Chem. 2016, 55 (3), 1315−1323.

(50) Fegade, U.; Sahoo, S. K.; Singh, A.; Mahulikar, P.; Attarde, S.; Singh, N.; Kuwar, A. A selective and discriminating noncyclic receptor for HSO4‑ ion recognition. RSC Adv. 2014, 4 (29), 15288−15292. (51) Anbu, S.; Kandaswamy, M.; Suthakaran, P.; Murugan, V.; Varghese, B. Structural, magnetic, electrochemical, catalytic, DNA binding and cleavage studies of new macrocyclic binuclear copper(II) complexes. J. Inorg. Biochem. 2009, 103 (3), 401−410. (52) Anbu, S.; Kandaswamy, M.; Varghese, B. Structural, electrochemical, phosphate-hydrolysis, DNA binding and cleavage studies of new macrocyclic binuclear nickel(II) complexes. Dalt. Trans. 2010, 39 (16), 3823−3832. (53) Thirumavalavan, M.; Akilan, P.; Kandaswamy, M.; Chinnakali, K.; Kumar, G. S.; Fun, H. K. Synthesis of Lateral Macrobicyclic Compartmental Ligands: Structural, Magnetic, Electrochemical, and Catalytic Studies of Mono- and Binuclear Copper(II) Complexes. Inorg. Chem. 2003, 42 (10), 3308−3317. (54) Sundaravadivel, E.; Vedavalli, S.; Kandaswamy, M.; Varghese, B.; Madankumar, P. DNA/BSA binding, DNA cleavage and electrochemical properties of new multidentate copper(II) complexes. RSC Adv. 2014, 4 (77), 40763−40775. (55) Saini, A. K.; Kumari, P.; Sharma, V.; Mathur, P.; Mobin, S. M. Varying structural motifs in the salen based metal complexes of Co(II), Ni(II) and Cu(II): synthesis, crystal structures, molecular dynamics and biological activities. Dalt. Trans. 2016, 45 (47), 19096−19108. (56) Tenover, F. C. Mechanisms of antimicrobial resistance in bacteria. Am. J. Infect. Control 2006, 34 (5), S3−S10. (57) Baddley, J. W.; Winthrop, K. L.; Patkar, N. M.; Delzell, E.; Beukelman, T.; Xie, F.; Chen, L.; Curtis, J. R. Geographic Distribution of Endemic Fungal Infections among Older Persons, United States. Emerging Infect. Dis. 2011, 17 (9), 1664. (58) Schiffmann, R.; Neugebauer, A.; Klein, C. D. Metal-Mediated Inhibition of Escherichia coli Methionine Aminopeptidase: Structure − Activity Relationships and Development of a Novel Scoring Function for Metal − Ligand Interactions. J. Med. Chem. 2006, 49, 511−522. (59) Poulter, N.; Donaldson, M.; Mulley, G.; Duque, L.; Waterfield, N.; Shard, A. G.; Spencer, S.; Jenkins, A. T. A.; Johnson, A. L. Plasma deposited metal Schiff-base compounds as antimicrobials. New J. Chem. 2011, 35 (7), 1477−1484. (60) Luo, L.; Li, G.; Luan, D.; Yuan, Q.; Wei, Y.; Wang, X. Antibacterial Adhesion of Borneol-Based Polymer via Surface Chiral Stereochemistry. ACS Appl. Mater. Interfaces 2014, 6 (21), 19371− 19377. (61) Ramalingam, B.; Parandhaman, T.; Das, S. K. Antibacterial Effects of Biosynthesized Silver Nanoparticles on Surface Ultrastructure and Nanomechanical Properties of Gram-Negative Bacteria viz. Escherichia coli and Pseudomonas aeruginosa. ACS Appl. Mater. Interfaces 2016, 8 (7), 4963−4976. (62) Bazaka, K.; Jacob, M. V.; Chrzanowski, W.; Ostrikov, K. Antibacterial surfaces: natural agents, mechanisms of action, and plasma surface modification. RSC Adv. 2015, 5 (60), 48739−48759. (63) Raj, T.; Kaur Billing, B.; Kaur, N.; Singh, N. Design, synthesis and antimicrobial evaluation of dihydropyrimidone based organicinorganic nano-hybrids. RSC Adv. 2015, 5 (58), 46654−46661. (64) Abu-Dief, A. M.; Mohamed, I. M. A. A review on versatile applications of transition metal complexes incorporating Schiff bases. Beni-Suef Univ. J. Basic Appl. Sci. 2015, 4 (2), 119−133. (65) Shao, W.; Liu, X.; Min, H.; Dong, G.; Feng, Q.; Zuo, S. Preparation, Characterization, and Antibacterial Activity of Silver Nanoparticle-Decorated Graphene Oxide Nanocomposite. ACS Appl. Mater. Interfaces 2015, 7 (12), 6966−6973. (66) Indoria, S.; Lobana, T. S.; Sood, H.; Arora, D. S.; Hundal, G.; Jasinski, J. P. Synthesis, spectroscopy, structures and antimicrobial activity of mixed-ligand zinc(ii) complexes of 5-nitro-salicylaldehyde thiosemicarbazones. New J. Chem. 2016, 40 (4), 3642−3653. (67) Lobana, T. S.; Indoria, S.; Kaur, H.; Arora, D. S.; Jassal, A. K.; Jasinski, J. P. Synthesis and structures of 5-nitro-salicylaldehyde thiosemicarb-azonates of copper(ii): molecular spectroscopy, ESI-mass 6079


Research Article

ACS Sustainable Chemistry & Engineering studies, antimicrobial activity and cytotoxicity. RSC Adv. 2015, 5 (20), 14916−14936.

6080


Syntheses and Photophysical Properties of Schiff ... - ACS Publications

Recommend Documents