New class of Platinum based metallosurfactant: Synthesis, micellization, surface, thermal modelling and in vitro biological properties

Accepted Manuscript New class of Platinum based metallosurfactant: Synthesis, micellization, surface, thermal modelling and in vitro biological properties

Nitin Kumar Sharma, Man Singh PII: DOI: Reference:

S0167-7322(18)31133-4 doi:10.1016/j.molliq.2018.07.041 MOLLIQ 9362

To appear in:

Journal of Molecular Liquids

Received date: Revised date: Accepted date:

5 March 2018 10 June 2018 10 July 2018

Please cite this article as: Nitin Kumar Sharma, Man Singh , New class of Platinum based metallosurfactant: Synthesis, micellization, surface, thermal modelling and in vitro biological properties. Molliq (2018), doi:10.1016/j.molliq.2018.07.041

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ACCEPTED MANUSCRIPT New class of Platinum based metallosurfactant: Synthesis, Micellization, surface, thermal modelling and in vitro biological properties Nitin Kumar Sharmaa,b and Man Singha a

School of Chemical Sciences, Central University of Gujarat, Gandhinagar, 382030, India b

Shri M.M. Patel Institute of Science and Research, Kadi Sava Vishwavidyalaya,

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Gandhinagar, Gujarat, 382023, India

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Corresponding author: Man Singh and Nitin Kumar Sharma Tel. No. 079-23260210, Fax No. 079-23260076 E-mail address: [email protected]; [email protected]

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ACCEPTED MANUSCRIPT Abstract Self-aggregation, thermogravimetric and biological evaluation of newly synthesized biscetylpyridiniumtetrachloroplatinate (Pt-CPC) metallosurfactant are reported. The Pt-CPC was synthesized using one step ligand insertion method and characterized with CHN analyser, FTIR, 1H NMR and Raman spectroscopy. Their critical micelle concentration

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(CMC) calculated by conductivity and surface tension measurements depicted faster self-

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aggregation on increasing temperature. The results indicate the influence of Pt metal

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responsible for lowering the CMC value of Pt-CPC than CPC. A higher thermal stability of Pt-CPC as compared to CPC were observed from thermogravimetric analysis. Five different

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sets of theoretical models were used to calculate the activation energy of Pt-CPC and CPC. The micellization was thermodynamically spontaneous and micelles formed were ellipsoidal

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in shape depicted by Scanning Electronic Microscopy (SEM) studies. Additionally, Pt-CPC was investigated for antimicrobial activity and cytotoxicity using human cancerous cells.

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Keywords: CPC; metallosurfactant; TGA; DTA; CMC

1. Introduction

The functionalization of transition metal such as Pt with varieties of surfactant has widely

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attracts the researchers in metallosurfactants.1-3 This attraction is due to the significance of

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platinum and surfactants in domain of material, catalytic and biological applications.1 The discovery of such metallosurfactant is inspired with a quasi-1-D [Pt(NH3)4]2+ [PtCl4]2material known as Magnus green salt comprising linear arrays of Pt (II) containing both cationic and anionic parts. By substituting the ammonia with linear and branched amino alkanes to produce Magnus salt derivatives for many industrial applications.2 Currently, different metals and surfactants are used to synthesize a multifunctional metallosurfactant with different stoichiometry and applications. A number of metals such as Pd, Ni, Fe, Co, Cu, Ag and many more with different cationic, anionic and neutral surfactant have already proven 2

ACCEPTED MANUSCRIPT their importance for the development of metallosurfactant.3-7 The surfactants are a known potential class of molecules were used for developing new materials with verities of biological applications. The n-trimethyl quaternary ammonium (CnQA), a cationic detergent whose surface-active configuration facilitates its rapid and prolonged incorporation into cell via lipid membranes.8 The n-trimethylammonium (CnTA) member of CnQA is frequently

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used as a preservative in several ophthalmic aqueous/non-aqueous solutions including

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nebulizer and nasal sprays.9 It is also useful as disinfectants, biocides, and detergents along with anti-electrostatics for phase transfer catalytic activities.10-11 Despite potential medicinal

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activities of CnTA, its chemical combination with metals like Pt has not much explored.12

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The selection of Pt metal is because of its historical importance in medicinal and material sciences.13 Different morphologies of metallosurfactants and their nanoparticles, including

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spheres, sheets, wires and tubes have been fabricated using a variety of techniques, including microwave, reduction, sono-chemical, biogenic, plant extract, etc.,14-17 and their different

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forms have been optimized for diverse applications ranging from catalysis, electronic circuits,

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optical devices, to gas sensors, and biosensors.18-21 Platinum, with its superior properties, is also being exploited as an antimicrobial,10,22 as well as an anti-cancer agent.23 In this article

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we have chosen Cetylpyridinium chloride (CPC) for the synthesis of new class InorganicOrganic hybrid metallosurfactant (IOHM). The selection of CPC, a cationic surfactant due to

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its effective metal extracting activity of platinum group through an anion exchange mechanism.22-23 In view of this, we have used [PtCl4]2- as metal centre and CPC as cationic surfactant for the synthesis of thermally and biologically active Pt based metallosurfactant (Pt-CPC). An ionic linkage between these two oppositely charged units led to coordinate into a quasi-1-D structure without bond formation.1,19-21 The newly synthesized Pt-CPC is analysed for micellization, kinetic and thermogravimetric studies, surface isotherm, surface morphology and biological activity. The anticancer and antimicrobial activities of both CPC

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ACCEPTED MANUSCRIPT and Pt-CPC were estimated using the SRB assay and disc diffusion methods respectively. This study supressed and upgrades the importance of Pt with cationic surfactant and its use in micelles vesicle transition. Over the years, such hybrids have profound applications in light emitting diodes, field-effect transistors, solar cells and the design of new mesoporous materials.24–30

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2. Experimental Section

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2.1. Materials used

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Potassium tetrachloroplatinate (Sigma Aldrich, A.R. grade, 99.99%), Cetylpyridinium chloride (Alfa Aesar, 99 %), acetone (Rankem, HPLC grade, $99.8%), Dimethyl sulfoxide

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(Rankem, HPLC grade, $99.8%) and Dimethylsulfoxide-d6 (Sigma Aldrich. 99.8% for NMR study) were used as received. The MiliQ water was used for solution preparation.

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2.2. Synthesis of Pt-CPC Metallosurfactant

The Pt-CPC were synthesized using our previously reported method.12 To obtain Pt-CPC, the

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K2PtCl4 and CPC were dissolved in water separately. The aqueous solution of CPC was

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added drop wise in K2PtCl4 solution on constant stirring at rt and the mixture left for 10 h. Their 1: 2 molar ratios produced pink colour solution followed by precipitation on

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completion of reaction in ≈ 3 h. Thereafter, stirring was stopped and the reaction mixture kept overnight to complete the precipitation. The product was filtered off and the pink ppts

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recrystallized several times with chilled water to remove the impurities and dried over fused calcium chloride and stored in a vacuum desiccator. 2.3. Instruments and detection methods 2.3.1. FTIR spectroscopy Fourier transform infrared spectra are recorded on Perkin Elmer spectrum 65 instrument with KBr palate with polystyrene thin film of 50 nm as a calibration standard at 25°C. The ≈ 2 mg Pt-CPC with 100 mg KBr was mixed, grinded and pressed in a compressor for preparing

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ACCEPTED MANUSCRIPT pellets. The spectra were scanned against a blank KBr pellet for background in 4000 to 400 cm−1 range with ±4.0 cm−1 resolution. 2.3.2. Raman spectroscopy Raman spectra for K2PtCl4 and Pt-CPC were recorded separately using Jobin Yvon Horibra LABRAM-HR visible with argon 488 nm laser. The 1µm area of sample was selected for

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high stability confocal microscope for micro Raman 10x. The 100 to 700 cm -1 regions were

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selected for detection of Pt-Cl bond.

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2.3.1. 1H NMR spectroscopy

H spectra in DMSO-d6 and D2O (Sigma Aldrich, 99.99%) were recorded with a Bruker-

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Biospin Avance-III 500 MHz FT-NMR spectrometer for CPC and Pt-CPC. 2.4. CMC determination

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CMC values were determined conductometrically using a specific conductivity meter by calibrated conductivity cell with 0.1, 0.01 and 0.001 M KCl solution.31-32 Their cell constant

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was calculated using molar conductivity for KCl.31-32 The conductivity for CPC and Pt-CPC

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in 0.2 volume fraction of DMSO in DMSO-water were measured at 298.15 K at 298.15, 308.15 and 318.15 K within ± 0.01 accuracy. The reason of using 0.2 volume fraction of

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DMSO in DMSO-water for a complete Pt-CPC solubility as compared to water and 0.1 volume fraction of DMSO. The equilibrium establishment for a series of readings in 15 min

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intervals was checked until no significant change occurred. 2.5. Surface tension isotherm determination Densities of CPC and Pt-CPC were measured using Anton Paar DSA 5000 M Densimeter, with the respective accuracies of ± 10-6 g cm-3. The instrument was calibrated with water and dry air. The surface tensions for CPC and Pt-CPC in 20% DMSO-water were measured using Borosil Mansingh Survismeter (BMS), with ±0.01 mN/m and ±1×10-4 mPa-s accuracies respectively.31-32 The temperature was maintained with Lauda thermostat with ± 0.01 C

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ACCEPTED MANUSCRIPT accuracy. The accuracy and calibration of instruments were made with the corresponding literature values.31-32 2.6. Thermogravimetric analysis Thermal stabilities were determined with a Mettler Toledo TGA 2 by heating samples in a 70 mL alumina pan from 30° C to 1100° C at a 10° C min-1 heating rate under 40 mL min-1 an air

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flow.

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2.7. Surface morphology

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SEM images with EVO18-18-69 model ZEISS SEM were obtained. The sample was adhered to, to holder and then made conductive in a coater chamber of Au (80%) and Pd (20%) by

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plasma sputtering.

2.8.1. Anticancer studies Cell

viability

was

estimated

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2.8. Biological investigation

calorimetrically

using

2-(3-

diethylamino-6

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diethylazaniumylidene-xanthen-9-yl)-5- sulfobenzenesulfonate, SRB (sulforhodamine B) as

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standard assay with high reproducibility.33 Human breast cancer cell lines MCF-7 and MDAMB-231 were obtained from NCI, USA, and grown in minimal essential medium (MEM).

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Eagles media were supplemented with 10% heat inactivated fatal bovine serum (FBS, SigmaAldrich), 2 mM L-glutamine and 1 mm sodium pyruvate (Hyclone) in humidified CO2

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incubator. Cytotoxicity of CPC and Pt-CPC were determined by SRB assay where E5000 cells were seeded into each well of a chamber having a 96 well clear flat bottom polystyrene tissue culture plate and incubated for 2 h in MEM. Again 190 mL cell suspension was added in each well containing 10 mL test sample in 10% DMSO with 10 mL Adriamycin (doxorubicin) as a positive drug control. Each experiment was carried out in 3 replicate wells. After an incubation of 48 h, the 100 mL of 0.057% SRB solution (w/v) was added in each well. Then 200 mL of 10 mM Tris base (pH 10.5) was added into each well followed by

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ACCEPTED MANUSCRIPT smooth shaking. The cell viability was assayed by absorption at 510 nm with a micro plate reader. The experiments were repeated thrice each time with 3 replicates. The 99% reproducibility was obtained using statistical analysis. 2.8.2. Antimicrobial studies The antibacterial screening of CPC and Pt-CPC were analysed against human pathogenic

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bacteria, namely, Gram-negative (Escherichia coli; NCIM 2109 and Pseudomonas

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aeruginosa; NCIM 2036), Gram-positive (Staphylococcus aureus; NCIM 2079 and Bacillus

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subtilis; NCIM2250) bacterial strains and two fungal strains (Candida albicans; NCIM 3471 and Aspergillus niger; NCIM 545) by Kirby Beurs Disc Diffusion Method using DMSO as

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solvent at 200 ??gmL−1 on Mueller Hinton Agar media. The inhibition zones were measured in millimetre (mm) after 24 h incubation at 37∘C and pH 7.4 and were compared with

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standard drugs chloramphenicol (10 ??g) and ciprofloxacin (10 ??g). Discs with only DMSO

3. Results and Discussion

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3.1. Structural characterization

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were used as positive control.

Structural confirmation of Pt-CPC is confirmed with CHN analyser, FTIR, and 1H NMR. The

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CHN data have indicated the calculated percentages of C, H, and N are in close agreement with experimental values (table 1). The molecular formula, weight, % yield, reaction time,

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melting point and colour are reported in table 1. 3.1.1. FTIR spectral studies The IR spectra furnish information about metallosurfactants for binding mode of cationic surfactant to anionic metal ion.34 The IR spectra of CPC is compared with Pt-CPC shows minor differences inferring their linkages. The bulk –CH2 as the surfactant is interacted, so they seem to the immobilized by Pt-N interaction. The 2915, 2848, 1468, 1380, 360, 339, 308, 294 /cm−1 of Pt-CPC with KBr confirm their structure (figure 1, table 2).28 The 400–

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ACCEPTED MANUSCRIPT 500 cm−1 predicted formation of new bands of low intensity infer CPC and metal ion linkage.28 As compared to CPC, two intense and sharp bands at 2915 and 2848 cm-l inferred an asymmetric and symmetric stretching vibrations of C-CH2 of methylene chains, respectively. No change is observed in hydrophobic chains of CPC on linkage with [PtCl4]-2 which acts as

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a UV transparent zone of the Pt-CPC. Similarly, the -CH2-CH2- stretching frequencies at

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1470 and 1481 cm-1 remain unaffected apart from their assumption which supports Pt-N

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interaction. The 1392 and 1407 cm-1 represent N-CH3 symmetric stretching vibrations with a peculiar shift confirming complexation. Similarly, a shift in a peak of terminal Cl from 325 to

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339, 360 cm-1 is accompanied by an appearance of bridging Cl (308, 294,252 cm-1) which also confirm a complexation.28

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3.1.2. Raman analysis

Spectra of K2PtCl4 and Pt-CPC indicates and supports the non-bonding interaction between

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[PtCl4]-2 and CPC. The peak appears at 100 to 400 cm-1 infer vibrations for Pt-Cl bonds,

3.1.3. 1H NMR analysis

H NMR spectra of CPC and Pt-CPC in DMSO-d6 generate a number of peaks corresponding

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summarized in table 3 and figure 2.

to δ values for different proton signals given in table 4 and spectra are presented in ESI figure

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1 and 2 for CPC and Pt-CPC respectively. The minor changes in δ of protons of Pt-CPC as compared to CPC is observed due to a nonbonding interaction of Pt-N. 3.2. Critical micelle concentration (CMC) values The micelles formed at a sharp concentration range are called CMC and have wider applications in areas of catalysis and drug delivery.35 A reduction in slope depicted micellization which were determined on fitting the data points above and below the reduced points to two straight line equations with two slopes. Both the equations were solved

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ACCEPTED MANUSCRIPT simultaneously to obtain an intersection point on concentration scale. Thus, the electron affecting ability of metal ion vis-a-vis alkyl chain length of CPC reflects its effect on CMC. Such activity of Pt in Pt-CPC indicates the binding activities of [PtCl4]-2.2[CPC]+. It facilitates to determine degree of counter ion binding (β) and CMC for CPC and Pt-CPC. On increasing concentration, the specific conductivity is increased, and their slope reduced after

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a specific Pt-CPC concentration at particular temperature. The breaking points in specific

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conductance vs concentration of CPC and Pt-CPC presented in figure 3 depicts a

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commencement of micelle formation. As compared to CPC, the lower CMC values found for Pt-CPC are given in table 5.

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3.2.1. Effect of temperature on the CMC

On increasing temperature, the CMC value and specific conductivity of CPC and Pt-CPC in

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0.2 volume fraction of DMSO in DMSO-water media increases due to an quicker micelle formation on increasing solvophobicity.36-37 Also, their CMC and degree of micellization (α)

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are increased along with, the pre (S1) and post (S2) micellar slopes. The lowest CMC value

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of CPC and Pt-CPC is found at 298.15 K and the highest at 318.15 K. The increase in temperature induces the motions of counter ions and hydrophilic part of CPC manifolds. It

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results an increase in conductivity and it’s CMC in accordance with conventional surfactants due to a decrease in hydration of hydrophilic group, favours micellization on increasing

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temperature.37 Reportedly, many metallosurfactant with several metal ions and cationic surfactants and their results are very close to our findings.28-29,38-39 3.2.2. Thermodynamics of micellization The CMC vs temperature relation furnishes information on hydrophobicity and head group interactions to derives thermodynamic parameters of micellization. A change in CMC with temperature is analysed in terms of phase separation or equilibrium for micellization.39-41 So

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ACCEPTED MANUSCRIPT standard Gibbs energy

, Enthalpy

and Entropy

of micellization are

calculated with following equations given as (1) (2)

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(3) where R, T and

are gas constant, absolute temperature and average degree of micellar

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ionization (micelle ionization degree) at CMC respectively as ratio between slopes of linear

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specific conductance vs [CPC]/[Pt-CPC] plots above and below CMC is considered. All thermodynamic parameters supporting micellization for CPC and Pt-CPC in 0.2 volume

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fraction of DMSO in DMSO-water are compared with CPC in water from literature in table

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5. The CMC values and thermodynamic parameters are calculated for CPC in 0.2 volume fraction of DMSO-water mixed solvent media are compared with the data reported by

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Bhattarai, et. al and found in close agreement and in the same order for CPC (table 5).39 on micellization of CPC and Pt-CPC

The higher negative

values depicts spontaneity of micellization. So, on increasing

values slightly decreased for CPC and Pt-CPC that indicating less

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temperature the

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3.2.2.1. Effect of

spontaneity of micellization at higher temperature. This proves that increased kinetic energy

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pushes the CPC and Pt-CPC to an optimized state (CMC) rather than at a cost of their chemical energies, thus, their spontaneity is decreased. The

values of CPC in 0.2

volume fraction of DMSO in DMSO-water were analysed at multiple temperatures and compared with Pt-CPC which found decreases and indicates a direct influence of [PtCl4]-2 counter part due to its ionic linkage with CPC (figure 4, table 5). 3.2.2.2. Effect of

micellization of CPC and Pt-CPC

A continuous decrease in supported by

on increasing temperature reflects an effect on micellization

(table 5 and figure 4) of Pt-CPC at a particular temperature. The electronic 10

ACCEPTED MANUSCRIPT interactions between head group of CPC and the counterion involve in disruption and association leading to exothermic and endothermic nature of Pt-CPC.42 The trends of and

on increasing temperature indicates, the

increases whereas the

value

decreases from higher to lower negative value. Data in table 5 explains the micellization as an

3.2.2.3. Effect of

on micellization of CPC and Pt-CPC

values increase (figure 4). The higher

values for Pt-

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On increasing temperature, the

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exothermic process.

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CPC depicts unfavourable entropic changes for micellization while least values favouring micellization due to orderings.

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3.2.3. Enthalpy-Entropy compensation phenomenon The variation in both

values show a mutual of enthalpy-entropy compensation , its counterpart noted as

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phenomenon. When the enthalpy contributes its less share to

for its lower values and vice versa. A linear

and is expressed with the help of equation (5).

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relationship is obtained from

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that contributes a larger share to

(5)

Where 1/Tc is slope and σ is intercept of linear plot. The Tc measures solvation part of

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micellization, the σ depicts solute-solvent interaction. It is considered as an index of chemical

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part of micelle formation (figure 5). The Tc values also favours the micellisation.29 Temperature dependence of hydrophobic effect is expressed as heat capacity of micellization and estimated from a slope of

vs temperature noted under as (6)

The

values decrease the heat holding capacity of Pt-CPC as compared to CPC which

favours its micellization (figure 6, table 6). The CPC with higher

due to entropically

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ACCEPTED MANUSCRIPT higher Brownian motions favours micellization. The lower

delays whereas the higher

values favour micellization. 3.2.4. Surface tension isotherm The surface tension isotherm and CMC of CPC and Pt-CPC are obtained by measuring surface tension at 298.15 K in 20% DMSO to check a validity of CMC calculated from

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conductivity experiment and showed a close agreement (figure 7a-b). It is reported that

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surface tension isotherm is obtained on plotting the graph between surface tension (γ) vs

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concentration of surfactant (logC). A surface tension isotherm is plotted in figure 7a-b. Figures 7a-b show that the at C > CMC, the surface tension is constant whereas at C < CMC

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the isotherm may be roughly divided into two regions. Region (I) the slope of curve γ decreases with logC while in region (II), the γ is a linear function of logC.

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3.3. TG-DTA analysis

TGA finds thermal behaviour of any material and determine various kinetic parameters of

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thermal decomposition and activation energy (E). Figure 8 depicts TG decomposition curves

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of Pt-CPC occurring in two steps. The Pt-CPC decomposition starts at ≈245-260°C, with an initial breakdown of quaternary ammonium moieties that continue up to 500 °C. The second

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step eventually degrades the metal chloride into metal.43-44 The % mass loss obtained experimentally are in close agreement with theoretical values (figure 8, table 7). The TGA

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finds a plausible mechanism for its decomposition is proposed in Scheme 1. Step 1.

Pt-CPC (s)

Step 2.

[PtCl4]2- (s)

2[CPC]+ + [PtCl4]2- (s) Pt (s) + 2Cl2 (g)

Scheme: Plausible mechanism for Pt-CPC thermal decomposition Kinetic and thermodynamic parameters of decomposition for first step The thermal activities at a fixed heating rate are depicted in figure 8 for their decomposition pattern. A small dip near 100 °C infer a loss of water molecules and from 247 to 252°C

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ACCEPTED MANUSCRIPT onwards infers a decomposition by releasing [CPC] chains and [PtCl4]-2. Primarily, two major mass loss regions are observed: the first region between rt and ≈ 250 °C is associated with a breakdown of Pt-CPC and the decomposition of quaternary ammonium structure. TG results obtained experimentally are in correct agreement with the calculated values (figure 8, table 7). Table 7 reports the activation energy required for Pt-CPC decomposition of using five

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methods. The higher values for Pt-CPC is obtained due to a higher thermal stability than

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precursor.28-29 The details of equations used and plots (linear fit) are given in figure 8.

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Five methods namely Coats-Redfern (CR), Madhusudanan Krishnan–Ninan (MKN), Wanjun–Yuwen–Hen–Cunxin (WYHC), Van Krevelen (VK) and Horowitz–Metzger (HM)

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for a single heating rate are used to calculate kinetic and thermodynamic parameters for a decomposition of step-1.28 The calculation for activation energy is made with the equations

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reported in literature.26-29 In all the methods α (degree of reaction) and in turn, g(α) (integral function of conversion) is estimated with several parameters, discussed below.

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1. Coats-Redfern (CR) method

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(8)

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Taking natural log

(7)

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A fractional mass loss (α) and corresponding (1- α) n are calculated from TG curve, where n depends on reaction model. for n ≠ 1

(9)

for n = 1

(10)

Plotting the left-hand side of equation (5) against 1/T gives slope (-2.303E/R) and intercept (A). 2. Madhusudanan Krishnan–Ninan (MKN) method 13

ACCEPTED MANUSCRIPT (11) 3. Wanjun–Yuwen–Hen– Cunxin (WYHC) method (12)

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4. Van Krevelen (VK) method

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5. Horowitz–Metzger (HM) method

(13)

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Parameters T= Tm+ are used for an order of reaction is 1 where Tm is defined as the

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temperature at which (1-α)m = 1/e = 0.368 that enabled the following relationship. (14)

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Symbols , Tm, E, A, R infer heating rate, DTG peak temperature, activation energy (kJmol ), pre-exponential factor (min-1) and gas constant (8.314 Jmol-1K-1), respectively. The

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excellent correlation coefficient indicates a good linear fit for all the methods (figure 8).

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Table 7 gives TGA data and value of activation energy obtained from five methods for first degradation step of CPC and Pt-CPC.

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So, an increase in activation energy for Pt-CPC infers higher thermal stability as compared to CPC with all five methods. The activation energies for CPC and Pt-CPC are presented in

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figure 9. The activation energies of metallosurfactants are calculated using TGA data which are compared with Pt-CPC and reported in table 8. Table 8 reflects the changes in activation energies on changing the metal ions as counter part of surfactant whereas our data indicate an effect of alkyl chain length of surfactant with a fix metal ion counterpart. Our studies explain a role of metal ion in surfactant of metallosurfactant contrary to previous studies only based on role of metal ion on a surfactant. 3.4. Surface morphology

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ACCEPTED MANUSCRIPT The surface morphology of self-assembled Pt-CPC are examined with SEM and EDX analysis.45-47 Pt-CPC is analysed for their surface morphology at different magnifications (figure 10). Their surface pattern shows reasonable dispersion in selected area. SEM images reflect spherical and homogeneous pattern of Pt-CPC on increasing magnification.48 The chain like aggregated surface of Pt-CPC inferred the similar morphology throughout the

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sample.

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3.5. Biological Assays

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3.5.1. In vitro cytotoxicity

The CPC and Pt-CPC were examined in vitro against MCF-7 and MDA-MB-231 human cancer

cell

lines

using

colorimetric

micro

culture

2-(3-diethylamino-6-

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breast

diethylazaniumylidene-xanthen-9-yl)-5-sulfo-benzenesulfonate (SRB) assay compared with

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Adriamycin (ADR).49 Figure 11(a-b) depicts anticancer activities of 10, 20, 40 and 80 µM of CPC and Pt-CPC against selected cell lines. Pt-CPC could not have expressed strong

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anticancer activities as compared to standard ADR having GI50 values <10 (figure 11, table

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9). The anticancer activities (GI50) of CPC and Pt-CPC expresses an effective anticancer potential much closer to ADR values (table 9). Similarly, LC50 dose of the CPC and Pt-CPC

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have been effective to control the growth of cancerous cells with higher GI50 values as of standard. It is found that the longer alkyl chain containing metallosurfactant expressed mild

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anticancer activity in terms of GI50 which is very closer to control drug is due to its hydrophobicity in metal coordination.28-29,50 The above-mentioned prospects highlighted their anticancer nature (GI50<10) in association with the Pt metal salt anion having CPC which increases the hydrophobicity on combining with metal salt could increase anticancer potential of Pt-CPC. 3.6. Antibacterial assays

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ACCEPTED MANUSCRIPT The antimicrobial activities of CPC and Pt-CPC were determined against pathogenic Grampositive bacteria (B. subtilis and S. aureus), Gram-negative bacteria (E. coli and P. aeruginosa) and fungi (C. albicans and A. niger) at 5 mg/mL concentration. Data in table 10, revealed that the CPC and Pt-CPC have antimicrobial activity depending on their alkyl chain length which have a close impact with results obtained in anticancer activity. It indicates that

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the optimal activity toward a variety of bacterial species for numerous structural variations of

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CPC and Pt-CPC, the obtained data are also in close agreement with the values reported

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elsewhere.51-58 It is reflected from table 10 that CPC has higher activity than the Pt-CPC against different microbes which is strictly different from the anticancer activity (figure 12).

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The Pt-CPC expressed their potential only on B. Subtilis, S. Aureus, E. coli and C. albicans whereas the CPC have shown its impact on all the microbes. The zone of inhibition for CPC

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is found more effective as compared to Pt-CPC, this could be due to weaker interaction between metallic anion and cationic surfactant. The data obtained from the results of

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antibacterial and antifungal studies reveal that Pt-CPC exhibit biological activity lower than

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CPC against one or more bacterial and/or fungal strains. Table 10 and figure 12 represents the antifungal activities against two potent fungal strains A. niger and C. albicans. The values of

studied fungi.

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4. Conclusion

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inhibition zones indicate cytotoxic efficacy of CPC as compared to Pt-CPC against the

Keeping the importance and applications of Platinum metal, the present work is an attempt to synthesize amphiphilic functionalities having Platinum, which can have a broad perspective in the future. For this purpose, Pt-CPC is synthesized by a simple methodology having {PtCl4]-2 and CPC. The Pt-CPC, an organic–inorganic hybrids were found to be thermally stable as compared to pure CPC. Their thermal decomposition studies have shown exothermic behaviour before transition temperature whereas on and after the transition

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ACCEPTED MANUSCRIPT temperature, the Pt-CPC have expressed an endothermic behaviour. The self-aggregation of the Pt-CPC and CPC in chosen solvent medium have examined using conductivity and surface tension. The observations revealed that the Pt-CPC underwent micellization at lower concentrations than their precursors. The

,

and other parameters had supports

micellization. The surface morphology and elemental composition were studied with SEM

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and EDX respectively and the result inferred the homogeneous morphology throughout the

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sample. In addition, the bioactivity of CPC and Pt-CPC have explored, which included

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biocompatibility testing using SRB assay, antimicrobial activity (fungus and bacteria), and cytotoxic analysis using human cancerous cells. Our study effectively reflects understanding

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of a new category of Pt based metallosurfactant with some tuneable properties which could be an interest in readers.

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Acknowledgment

Authors are thankful to Central University of Gujarat, Gandhinagar for infrastructural support

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and experimental facilities. NKS is also thankful to Baljeet Singh, Tata Institute of

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Fundamental research, Mumbai, India for thermogravimetric studies respectively.

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7. Zhang, C.; Zhu, Y.; Zhou, C.; Yuan, W.; Du, J., Polym. Chem., 4 (2013) 255-259. 8. Green, K.; Chapman, J. M.; Cheeks, L.; Clayton, R.M.; Wilson, M.; Zehir, A.,

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ACCEPTED MANUSCRIPT 36. Zielinski, R.; Ikeda, S.; Nomura, H.; Kato,S., J.Colloid & Int.Sci. 129 (1989) 175184. 37. Patil, R.S.; Shaikh, V.R.; Patil, P.D.; Borse, A.U.; Patil, K.J. , J. Chem. Eng. Data, 61 (2016) 95–206. 38. Kaur, G.; Kumar, S.; Kant, R.; Bhanjana, G.; Dilbaghi, N.; Guru, S.K.; Bhushan, S.;

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Polym. Sci. 280 (2002) 503-508.

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44. Keuleers, R.; Janssens, J.; Desseyn, H.O., Thermochim. Acta 354 (2000) 125-133. 45. Wu, X.; Tian, Y.; Yu, M.; Han, J.; Han, S., Biomater. Sci. 2 (2014) 972-979.

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ACCEPTED MANUSCRIPT 51. G.M. Sulaiman, E.H. Ali, I. I. Jabbar, A. H. Saleem, Digest J. Nanomat. Biostruc. 9 (2014) 787-796. 52. Q.L. Feng, J. Wu, G.Q. Chen, F.Z. Cui, T.N. Kim, J.O. Kim, J.Biomed. Mater. Res. 52 (2000) 662-668. 53. J. Tang, Q. Chen, L. G. Xu, S. Zhang, L. Z. Feng, L. Cheng, H. Xu, Z. Liu, R. Peng, ACS Appl. Mater. Interfaces. 5 (2013) 3867-3874.

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54. M. Nocchetti, A. Donnadio, V. Ambrogi, P. Andreani, M. Bastianini, D. Pietrellac L. Latterinia, J. Mater. Chem. B, 1 (2013) 2383-2393.

55. Y. Xia, C. Cheng, R. Wang, C. Nie, J. Denga, C. Zhao, J. Mater.Chem. B, 3 (2015)

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9295-9304.

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56. N. Stavgianoudaki, K.E. Papathanasiou, R.M.P. Colodrero, D.C. Lazarte, J.M. Ruiz, A. Cabeza, M.A.G. Aranda, K.D. Demadis, CrystEngComm. 14 (2012) 5385-5389.

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57. S.M. Tawfik, M.F. Zaky, J. Surf. Deterg. 18 (2015) 863-871. 58. H.S. Galal, F.M. Ghuiba, M.I. Abdou, E.A. Badr, S.M. Tawfik, N.A. Negm, J. Surf.

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Deterg. 15 (2012) 735-743.

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ACCEPTED MANUSCRIPT Figure 1. FTIR spectral pattern of CPC against Pt-CPC. Figure 2. Raman spectra of K2PtCl4 and Pt-CPC Figure 3. Variation of CMC (a) CPC, (b) Pt-CPC in 0.2 volume fraction of DMSO in DMSO- water at 298.15, 308.15 and 318.15 K and (c) lnXcmc vs T and

on Pt-CPC at chosen temperature

Figure 5. Linear relationship and contribution of of micellization

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Figure 6. Heat capacity (

with

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Figure 4. Effect of

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Figure7a-b. Schematic representation of surface tension isotherm of water/surfactant solution.

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Figure 8. Thermogravimetric (TG) analysis of Pt-CPC

Figure 9. Comparative activation energy of CPC and Pt-CPC

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Figure 10. Surface morphological images of Pt-CPC (a) SEM at 1µm, (b) SEM at 2 µm and (f) EDX.

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Figure 11. Cytotoxic studies for CPC and Pt-CPC on (a) MCF-7 and (b) MDA-MB-231 cell lines.

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Figure 12. Zone of inhibition on CPC and Pt-CPC against the microbes compared with their

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control drug.

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ACCEPTED MANUSCRIPT

List of tables

Molecular weight

Reaction solvent

Melting point

C32H76Cl4N2Pt

945.95

aqueous

141.2

% Yield

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Molecular formula

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Name

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Table 1. Characterization data of Pt-CPC

Colour

78

Light green

Elemental analysis

Pt-CPC

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Found (%) H 8.10

N 2.96

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C 53.33

Calculated (%)

C 53.82

H 8.76

N 4.01

Table 2. FTIR stretching frequencies (cm-1)

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Functional groups Aromatic C–H stretching

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C=C and N-C sym stretching

Terminal Cl Bridging Cl

Pure CPC 3051 3008 3328 2895 2848 1377 1054 2162 1636 1178 325 …

Pt-CPC 3047 … … 2917 2854 1495 1173 … 1633 1172 327 283

Table 3. Raman study for the detection of [PtCl4]-2 and Pt-CPC frequencies. Vibrations f(Pt-Cl, Pt-Cl’) f(Pt-Cl) f(Pt-Cl, Pt-Cl”)a f(Cl-Pt-Cl’, Cl-Pt-Cl”)

Frequencies (cm-1) 305 328 173 313, 165

Symmetry B1g A1g B2g Eg 23

ACCEPTED MANUSCRIPT f(Cl-Pt-Cl’) f(Pt-Cl, Cl-Pt-Cl”)

147 112

A2u B2u

1

CPC Pt-CPC

CH3-(CH2)1.918 1.898

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CH3 0.861 0.865

H NMR in DMSO-d6 (CH2)n (CH2)n-N(CH3)3 1.245 4.661 1.243 4.598

N(CH3)3 8.179-9.127 8.172-9.110

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Entry 1 2

Complexes

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Table 4. 1H NMR of CPC and Pt-CPC in DMSO-d6

Table 5. CMC and thermodynamic parameters of CPC and Pt-CPC in 0.2 volume fraction of

CMC

Β

298.15

198

46.8

0.32

0.764

308.15

222

53

0.44

0.761

318.15

241

59

0.58

0.755

298.15

50.2

14.8

2.38

0.705

308.15

51.5

15.5

2.421

318.15

52.1

15.9

2.51

*

ΔGm

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S2

ΔHm

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CPC

S1

Bhattarai, et. al ΔSm

CMC

ΔGm

ΔHm

ΔSm

-21.854

-38.45

-0.0557

-20.445

-38.40

-0.0602

-19.185

-38.27

-0.0640

-12.828

-3.21

0.0322

2.95

-36.47

-14.85

72.53

0.699

-12.714

-3.20

0.0319

3.0

-36.37

-15.32

68.33

0.695

-12.538

-3.19

0.0313

3.65

-35.77

-15.77

62.87

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Pt-CPC

Temp

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DMSO.

The error limits of CMC, ΔGm ΔHm, and ΔSm, are ±3, ±4, ±3, ±5, ±4 and ±4% respectively.

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Complexes CPC Pt-CPC

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Table 6. Values of Tc, σ and

for Pt-CPC using conductivity measurement Compensation parameters

Tc (K) 23.87 21.98

σ 1.669 0.114

(J. mole-1K-1) 9.2 1.0

Table 7. TGA data and activation energy calculated for Pt-CPC CPC Decomposition step

Transition Mass loss % Temperature Calc. Obs. (°C) Step1 259.84 96.19 96.56 Step 2 Activation energy at transition temperature

Pt-CPC Transition Mass loss % Temperature Calc. Obs. (°C) 259.2 39.72 40.01 399.8 65.52 65.88

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ACCEPTED MANUSCRIPT E/ kJmol-1 40.84 40.84 40.69 45.03 45.20

Methods R CR 0.9998 MKN 0.9991 WYHC 0.9993 VK 0.9992 HM 0.9996 (R = Regression coefficient)

E/kJmol-1 83.88 87.19 83.85 87.89 83.10

R 0.9996 0.9995 0.9874 0.9995 0.9988

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Table 8. Some recent studies on similar metallosurfactant and their activation energies

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calculated by all five methods using TGA data compared with our studies.

MKN

WYHC

VK

PdCTACᵃ (C16 chain)

96.89

97.01

97.03

97.00

99.94

MnC I (C16 chain) MNC II (C16 chain) CTA-AgB (C16 chain) MHDTA (C16 chain) Pt-CPC (C16 chain)

32.48 51.80 28.05 156.18 83.88

33.95 52.95 28.21 156.52 87.19

34.01 53.19 28.26 156.64 83.85

36.13 57.31 32.59 184.59 87.89

38.25 58.98 32.58 156.37 83.10

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CR

Metallosurfactant

HM

References [21]

[22] [23] [12] Current work

1. 2. 3.

Complex CPC Pt-CPC ADR

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Entry

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complex, an anticancer analysis.

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Table 9. LC50, TGI and GI50 values (µM) against MCF-7 and MDA-MB-231 cell lines of

LC50 >80.0 >80.0 79.2

MCF-7

MDA-MB-231

TGI 71.8 74.3 40.5

GI50 26.5 21.8 <10.0

LC50 >80.0 >80.0 39.85

TGI 33.2 35.6 <10.0

GI50 22.7 19.6 <10.0

Entry 1 2 3 4

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Table 10. Antimicrobial activity of CPC and Pt-CPC

Sample

CPC Pt-CPC Ciprofloxacin Amphotericin B

Gram positive B. S. subtilis aureus 12.75 13.54 7.06 8.99 28.68 26.25 NA NA

Gram negative P. E. aeruginosa coli 12.17 12.9 -6.91 15.03 26.77 NA NA

Fungi C. albicans 15.37 7.26 NA 10.12

A. niger 10.98 -NA 14.54

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ACCEPTED MANUSCRIPT Highlights

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 The Pt-CPC are thermally stable and belongs from a new class of Pt based metallosurfactant.  The quick micelle formation is observed on incorporation of Pt in the cationic surfactants.  The biological activities of Pt-CPC are found attractive against different cell lines and microbes.  The thermodynamic parameters support its spontaneity towards micellization.

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Graphics Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12