thermo-physical examination: synthesized 2-furano-4(3h)-quinazolinone and open quinazolinone...

Accepted Manuscript

Title: Thermo-physical examination: Synthesized2-furano-4(3H)-quinazolinone and open quinazolinone(diamide) anticancer analogs with sodium dodecyl sulfate

Author: Varun Bhardwaj Poonam Sharma Malleshappa N.Noolvi Harun M. Patel S. Chauhan M.S. Chauhan KundanSharma

PII: S0040-6031(13)00477-2DOI: http://dx.doi.org/doi:10.1016/j.tca.2013.09.013Reference: TCA 76626

To appear in: Thermochimica Acta

Received date: 15-7-2013Revised date: 6-9-2013Accepted date: 10-9-2013

Please cite this article as: V. Bhardwaj, P. Sharma, M.N. Noolvi, H.M.Patel, S. Chauhan, M.S. Chauhan, K. Sharma, Thermo-physical examination:Synthesized 2-furano-4(3H)-quinazolinone and open quinazolinone (diamide)anticancer analogs with sodium dodecyl sulfate, Thermochimica Acta (2013),http://dx.doi.org/10.1016/j.tca.2013.09.013

This is a PDF file of an unedited manuscript that has been accepted for publication.As a service to our customers we are providing this early version of the manuscript.The manuscript will undergo copyediting, typesetting, and review of the resulting proofbefore it is published in its final form. Please note that during the production processerrors may be discovered which could affect the content, and all legal disclaimers thatapply to the journal pertain.

http://dx.doi.org/doi:10.1016/j.tca.2013.09.013

http://dx.doi.org/10.1016/j.tca.2013.09.013

of 35

Accep

ted

Man

uscr

ipt

1

Thermo-physical examination: Synthesized 2-furano-4(3H)-quinazolinone and open quinazolinone (diamide) anticancer analogs with sodium dodecyl sulfate

Varun Bhardwaj a, Poonam Sharma a,*, Malleshappa N. Noolvi b, Harun M. Patel c, S. Chauhan d, M.S. Chauhan d, Kundan Sharma d

aDepartment of Biotechnology, Bioinformatics and Pharmacy, Jaypee University of Information Technology, Waknaghat, Solan (Himachal Pradesh) 173234 India. bDepartment of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim, (Surat) Gujarat 394110 India. cDepartment of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur (Dhule) 425405, Maharashtra, India. dDepartment of Chemistry, Himachal Pradesh University, Summer hill, Shimla (Himachal Pradesh) 173005 India.

Corresponding Author (*):

Dr. Poonam Sharma, Tel: +91-1792-239389, Fax: +91-1792-245362

Email: [email protected] , [email protected]

of 35

Accep

ted

Man

uscr

ipt

2

Abstract

In this study, the solution and self aggregation properties of sodium dodecyl sulfate (SDS) in

presence of synthesized small molecules i.e. 3-(2-chloro benzylideneamine))-2-(furan-2-yl)

quinazoline-4(3H) one (Q1) and N-(2-(p-tolyl carbamoyl) phenyl) furan-2-carboxamide (Q2)

has been determined. The two compounds were earlier screened for anticancer activity from

NCI, USA. In order to investigate the physico-chemical properties, simple and controlled

methods were employed to obtain critical micellar concentration (CMC) values and thermo-

acoustic parameters via conductance, compressibility coefficient (β), apparent molar volume

(φv) and apparent molar adiabatic compressibility (φk) of SDS in the presence of Q1/Q2 at

different temperatures (25, 30, and 35 °C). In addition, the effect of the addition of Q1/Q2 in

SDS solution and to gain information regarding interaction between the molecules, FTIR and

1H NMR spectroscopic analysis was also carried out. The presence of different substitutions

on the molecules affecting SDS behavior has also been discussed.

Keywords: Quinazolinone; Thermodynamic; Spectroscopic analysis

of 35

Accep

ted

Man

uscr

ipt

3

1. Introduction

Quinazolines, the derivatives of benzo-pyrimidine are the compounds used in the

pharmaceutical industry, in medicine and even in agriculture because of their wide spectrum

of biological activities [1]. The quinazoline skeleton appears in many alkaloids, most

commonly in the form of 4-(3H)-quinazolinone moieties [2]. There is an evidence to suggest

that the introduction of additional heteroatoms into a drug molecule is potentially better for

increased bioactivity along with altering physiochemical properties and factors, such as

solubility and stability [3]. As quinazoline or quinazolinone includes wide range of biological

activities, it can be considered to be a versatile structure. A wide range of literature shows

that quinazoline compounds possess antihistamine [4], antiviral [5], antimicrobial [6], and

antimalarial properties [7]. Quinazoline have demonstrated anticancer and a range of other

central nervous system effects [8-10]. On the other hand, surfactants are amphiphilic

molecules consisting of polar (hydrophilic) and non-polar (hydrophobic) parts. These

molecules are of commercial important because of their amphiphilic structure which is

responsible for causing them to concentrate at interface or to undergo aggregation i.e.

formation of micelle [11]. Thermodynamic behavior of a solid in a liquid plays an important

role in drug design as well as in optimization of production processes. Micrometric and sub

micrometric particles of pharmaceutical and related compounds like hydrophobic enzymes,

anti-inflammatory drugs, anti-cancer drugs, antibiotics and biopolymers can be formed by

employing the SCF-GAS technique, where the application of an anti-solvent decreases the

solubility of a material dissolved in the solution. Surfactants have been of tremendous

scientific importance because of their many promising applications in detergents, cosmetics,

material fabrication, and drug delivery, among other areas [12]. The degree of solubilization

and the site occupied by the solubilizate depend upon the structural and chemical nature of

of 35

Accep

ted

Man

uscr

ipt

4

both the surfactant and the solubilizate as well as the concentration of the species in solution

and the temperature. The presence of the solubilizate can affect the process of micellization

and affects the thermodynamics of the micellization via interactions [13]. Two newly

synthesized molecules have been considered in this study as shown below and denoted as Q1

and Q2.

The choice of these two compounds is based on our previous study where the compounds

were synthesized rationally targeting EGFR tyrosine kinase (TKs) and were screened for

anticancer activity at National Cancer Institute (NCI), USA at a single high dose (10-5 M) in

full NCI 60 cell panel and five dose assay [14]. However, quinazoline is an important moiety

in drug industry, the activity in addition to different substitutions of these molecules attracted

us to study their behavior in hydro-ethanolic mixture i.e. 43.36 weight (%) ethanol + water

mixture. With this profile of ring system we intended to investigate their effect on SDS

properties. In this context, the present paper describes the structural effect, micellar study and

thermodynamic parameters. Spectroscopic study was also taken into account to provide

insight on the interactions and locus of the molecules within the surfactant micelle. In

continuation of our study on pharmaceutical active molecules [15-17] and their interaction

with surfactants, here we report the impact of Q1 and Q2 on SDS physicochemical properties.

The similar kind of literature reveals the importance and application of physicochemical

of 35

Accep

ted

Man

uscr

ipt

5

parameters/evaluation in pharmaceutical and food science [18-24]. This study therefore will

provide the hint of designing new molecules as bioactive compounds via kind of interactions

occurring with sulpho, chloro and amide substitutions on specific ring system.

2. Experimental

2.1. Material

Sodium dodecyl sulfate (SDS) of AR grade and purity > 99% and ethanol absolute (purity

≥ 99.9 %) was obtained from Merck Chemicals (Germany). Freshly prepared doubly distilled

water was utilized, prepared from double distillation unit (HARCO & Co.) whose specific

conductance and pH is in the range ≈ (1-4) × 10-7 S cm-1 and 6.5-7.0 at 25 °C respectively.

Compounds namely, 3-(2-chloro benzylideneamine))-2-(furan-2-yl) quinazoline-4(3H) one

(Q1) and N-(2-(p-tolyl carbamoyl) phenyl) furan-2-carboxamide (Q2) were synthesized

according to the procedure given in our earlier finding. The HPLC purity % area of Q1 and

Q2 were found 96.35 and 94.17, respectively. The structural characterization was carried out

using FTIR, NMR and Mass spectroscopy as given below [14].

Q1: Melting point 201-204 °C; IR (KBr) �max 2920, 1650, 1488, 1399, 554 cm-1; 1H NMR

(DMSO-d6) δ ppm: 7.09 (t, 1H, J = 4.0 Hz, furan-H), 7.50-8.25 (m, 10H, Ar-H and furan-H),

8.79 (s, 1H, N=CH); 13C NMR (DMSO-d6) δ ppm: 169.1, 160.4, 144.2, 142.3, 141.8, 140.3,

134.6, 132.2, 132.1, 131.4, 130.4, 127.4, 127.1, 125.6, 125.9, 120.3, 108.8, 108.9; HRMS

(EI) m/z calcd for C19H12ClN3O2: 349.0618; found:349.0622.

Q2: Melting point 188-189 °C; IR (KBr) �max 3350, 2913, 1676, 1624,1606, 1505, 1453,

1328,1140 cm-1; 1H NMR (DMSO-d6) δ ppm: 3.43 (s, 2H, NH2), 7.68 (d, 1H, J = 8.0 Hz, Ar-

H), 6.57-7.98 (m, 10H, Ar-H and furan-H) 10.53 (s,1H,-NHCO-), 11.71(s,1H,-CONH-); 13C

NMR (DMSO-d6) δ ppm; 168.5, 163.7, 146.7, 142.8, 141.4, 136.4, 135.5, 130.2, 128.7,

of 35

Accep

ted

Man

uscr

ipt

6

127.6, 124.4, 122.3, 118.6, 116.3, 114.4, 112.3; HRMS (EI) m/z calcd for C18H15N3O5S:

385.0732; found: 385.0735.

2.2. Apparatus and methods

Specific conductance (κ) was obtained using Cyber Scan CON-510 and the conductivity cell

was calibrated with 0.01 mol dm-3 KCl sample solution supplied by Merck Chemicals. The

uncertainty of the conductivity measurement was estimated to be ± 0.5%. The temperature

was maintained constant at ± 0.1 °C by circulating thermostat through a double walled vessel

containing the solution. The concentration of Q1 and Q2 was fixed i.e. 0.01 and 0.02 mol

Kg-1, respectively. All the density (ρ) and ultrasonic velocity (u) measurements has been

executed in a digital high precision instrument, DSA- Anton Paar Digital 5000 with range of

temperatures from 25-35 °C at an interval of 5 °C. All the samples were prepared 24 hours in

advance to settle the time dependent effect. The reproducibility of ultrasonic sound velocity

and density has been ± 0.2 ms-1 and ± 2 × 10-6 gcm-3 respectively over the entire

concentration and temperature range of measurements. Density and sound velocity data was

further utilized to calculate various parameters such as the compressibility coefficient (β),

apparent molar volume (φv) and apparent molar adiabatic compressibility (φk). FTIR and

proton-NMR spectra of the compounds were recorded to analyze interaction and location of

Q1 and Q2 within micelle. FTIR spectra were recorded at a frequency range of 4000-400

cm-1 with match pair of quartz cells using Shimadzu Infra Red Spectrometer, (model FTIR-

8400S). Proton-NMR was recorded with Bruker Avance-II 400 NMR spectrometer operating

at 400 MHz. The chemical shifts were considered and measurement of various resonant peaks

with respect to internal standard TMS are given on the δ scale in parts per million (ppm).

3. Result and Discussion

of 35

Accep

ted

Man

uscr

ipt

7

3.1. Conductance study:

The micellization behaviour of SDS has been traced in presence of Q1 and Q2 in hydro-

alcoholic solution i.e. 43.36 weight (%) ethanol + water mixture. The choice of short chain

alcohol was based on its nature of getting solubilized in aqueous phase and affecting the

process of micelle formation by modifying the solvent properties. Fig. 1 represents the

conductivity plot as a function of SDS concentration at three different temperatures at 5 °C

interval. The intersection point of the two straight lines represents the usual critical micellar

concentration (CMC). The effect of increasing temperature and SDS concentration has also

been observed. It is remarkable to note that in presence of Q1 and Q2, CMC is less than to

SDS’s region of micellization i.e. 8 mmol Kg-1 [25]. From the obtained values of CMC in

presence of Q1 and Q2, it is clear that Q2 produces a stronger reduction effect on micelle

formation of SDS than Q1. This decrease in the CMC value, mainly attributed to the

interactions between the synthetic molecule and amphiphilic moiety i.e. SDS and is

characteristic of amphiphiles of opposite charges. The CMC values of surfactant increases

with temperature and presence of amino and diamide groups in Q2 contributes eminently for

better interaction and therefore causing shift in micellization to much earlier. The Xcmc data

reported in Table 1 was further utilized to calculate various thermodynamic parameters. The

standard enthalpy, entropy and Gibbs free energy of micellization (ΔH°m, ΔS°

m and ΔG°m)

were calculated by using following equations [26].

ΔH°m = - RT 2 (2-α) [d ln(Xcmc)/dT ]

ΔS°m = (ΔH°

m - ΔG°m)/T

ΔG°m = R T (2-α) (ln Xcmc)

of 35

Accep

ted

Man

uscr

ipt

8

In the given equations, α denotes the degree of ionization of surfactant which was obtained

using relation, α = S2/S1, S1 and S2 are the slopes in the pre micellar and post micellar region

and d ln (Xcmc)/dT is the slope of the straight line obtained by plotting ln Xcmc against

temperature. All the values of ΔG°m and ΔH°

m were found to be negative revealing

exothermic behavior of the surfactant whereas ΔS°m were positive indicating that

micellization is entropically controlled. The values of ΔG°m with Q1 were found less negative

which might be because of steric hindrance of micelle formation as shown in Table 1 and Fig.

2. The ΔH°m values do not vary significantly with increase in temperature. Here, it can be

understood by assuming that London dispersion interactions represent the main attractive

force for micelle formation [27]. Therefore it is suggested that micellization is facilitated by

the presence of Q1 and Q2 with respect to solvent composition used and temperature as well.

Moreover, Q2 with higher negative ΔG°m values is solubilized to greater extent and has

tendency to transfer from dispersed to the micellar phase.

3.2. Volumetric and compressibility study:

The density (ρ) in addition to sound velocity (u) was obtained which provides information

regarding different interactions with respect to behavior of Q1 and Q2 in hydroalcoholic

solution. The study was performed at 25, 30 and 35 °C in water-ethanol composition [43.36

weight (%)] containing fixed concentration of Q1 (0.01 mol Kg-1) and Q2 (0.02 mol Kg-1) as

reported in Table 2. The increase in temperature favors the increase of kinetic energy and

volume expansion resulting in decrease of density, moreover suggests that thermal energy is

greater than the interaction energy at higher temperatures. The density and speed of sound

data is reported in Table 2 and was further utilized for calculating apparent molar volume (φv)

and apparent molar adiabatic compressibility (φk) using relation [28] as:

of 35

Accep

ted

Man

uscr

ipt

9

φv = (do-d)/mddo + M/d

φk = (β-βo)/mdo + φv β

Where, m is the molality of the solution, M is the molecular mass of SDS (288.38 gmol-1), d

(kgm-3) is the density of the solution, do is the density of the pure solvent system. Similarly, β

and βo denotes respectively for adiabatic compressibility coefficient of the solution and

solvent. The values for β were calculated using β= 1/dv2. Both properties are highly sensitive

to the extrinsic experimental conditions and therefore are suggested to be relevant to extract

information, especially with regard to the existence of solute-solute and solute-solvent

intermolecular interactions [29]. All the values of φv were found positive in prepared

composition at all temperatures as reported in Table 3. Fig. 3 and Fig. 4 describe the behavior

of φv in presence of Q1 and Q2. Errors in φv and φk values were calculated and found to lay in

the range ± 0.4 m3mol-1 and ± 0.1 m3mol-1TPa-1 respectively. It was observed that at initial

SDS concentration ionic interactions dominate which decreases as concentration of SDS

molecules increases within the environment, whereas at higher SDS concentration

hydrophobic-hydrophobic interactions become more dominant among the molecules leading

to micellization of SDS. Hence, making - breaking of structure strengthen the hydrophobicity

of SDS molecules and facilitates the process of micelle formation. It is clear from the

conductance study that Q2 produces a stronger effect on SDS properties which might be

because of the presence of -NH2- or the diamide in its structure. Moreover, the presence of

carbonyl group which has the active oxygen atom with capability of accepting or donating

electron according to the envionmental condition. These pharmacophore probably

contributing more efficiently in association to SDS and moreover affecting the

physcicochemical behavior of SDS. The anomalous behavior is also suggestive of association

of 35

Accep

ted

Man

uscr

ipt

10

of some kind of hydrophobic clustering of alcohol molecules. The φk versus SDS

concentration illustrates the same pattern as that of φv, thus supporting each other.

3.3. FTIR and 1H-NMR analysis:

To get more insight on the structure and intermolecular interaction occurring due to the

presence of different function groups on SDS and Q1/Q2, the system is characterized by

Fourier Transform infrared spectroscopy (FTIR) [30,31]. The existing structural changes are

interpreted in terms of frequency or band shift as presented in Fig. 5 (a,b,c). The methylene

anti-symmetric and symmetric vibrations have been clearly observed at 2957 cm-1, 2851 cm-1,

and 2919 cm-1 for alkyl -CH- stretching and 1469 cm-1 for alkyl -CH- deformation,

respectively. The spectrum of SDS depict bands at 1222 cm-1 and 1082 cm-1, signifying -S=O

(stretching) vibrational modes of sulphonic acid group present in SDS. The presence of

Q1/Q2 effect was observed via substantial shifting of bands as presented in Fig. 5(b) and

5(c). The band due to -S=O stretching vibrations in presence of SDS shifted to 1220 cm-1 and

1079 cm-1 in presence of Q1, in addition, -CH- vibrations were observed at 2922 cm-1 , 2958

cm-1 and 2852 cm-1. On the other hand in presence of Q2, -S=O stretching vibrations shifted

to 1224 cm-1 and 1077 cm-1 moreover -CH- vibrations were obtained at 2929 cm-1 , 2959 cm-1

and 2855 cm-1. The kind of shifting clearly depicts that the environment is tightly packed and

indicating that Q2 molecule is more interactive and bounding more efficiently than Q1.

To obtain more understanding into the interaction between the moieties and the locus

of Q1/Q2, proton nuclear magnetic resonance [32] of the SDS system both in the absence and

presence of Q1/Q2 were recorded. Due to the precision of the NMR spectrometer, a change

of ~ 0.01 ppm or greater is considered a significant change. The 1H NMR spectrum of SDS

and SDS in presence of Q1/Q2 is presented in Fig. 6 (a,b,c). The intense resonances at ~ 3.83

of 35

Accep

ted

Man

uscr

ipt

11

ppm and ~ 1.57 ppm corresponding to α -CH2- and β -CH2- as shown in structure of SDS.

However, moving toward hydrophobic part of SDS, the resonance at ~ 1.25 ppm and ~ 0.87

ppm with integral of 18 protons and 3 protons correspond to bulkier chain -(CH2)9- of SDS

and -CH3- group, respectively (SDS structure shown in figure below).

The chemical shift was observed with the addition of Q1/Q2 in SDS, particularly, α -CH2-, β

-CH2- and -(CH2)9- segments of SDS. The α -CH2- showed upfield movement with a shift of

~ 0.123 ppm. The β -CH2- and -(CH2)9- segments of SDS showed downfield movement of

~ 0.012 ppm and ~ 0.015 ppm, respectively (Fig. 6 b). This might be because of the presence

of electronegative group present in Q1 causing deshielding. The upfield movement of

α -CH2- is due to preliminary interaction of SDS molecule and exposed hydrophobic part of

Q1. On the other hand, the shifts were noticed at higher side in presence of Q2. The upfield

movement of ~ 0.213 ppm was observed for α -CH2- whereas β -CH2- and bulkier segments

of SDS showed movement of ~ 0.013 ppm and ~ 0.028 ppm, respectively as shown in Fig. 6

(c). Interestingly, the resonance of -CH3- protons were observed with ~ 0.014 ppm shift in

presence of Q2 which was absent in case of Q1. This clearly reveals the penetration of Q2

toward the core of micelle in comparison to Q1 which lies at interface or outer surface of the

micelle. This might also be possible that carbonyl group or sulfonic part interacts with

surfactant chain segment and significantly leading to deeper penetration of Q2 toward

of 35

Accep

ted

Man

uscr

ipt

12

micellar core. A hypothetical model representing interaction of Q1 and Q2 at site is presented

in Fig. 7.

4. Conclusion

Conclusively, the dependence of micelle formation of SDS in presence of Q1/Q2 with respect

to temperature and solvent composition is observed. Decrease in CMC in presence of Q2 is

because of the dilution of micellar surface charges which leads to faster aggregation of

surfactant molecules into micelles. From thermodynamic study, the values of ΔG°m suggested

that the process of micellization is spontaneous which was confirmed by negative values of

ΔH°m. The values of ΔS°

m indicate that micelle formation in this studied system is

entropically controlled. The variation of φv and φk values provided valuable information

regarding the structural rearrangement of the constituent molecules i.e. Q1/Q2 and surfactant

thereby indicating electrostatic and hydrophobic interactions as the main driving forces

involved in formation of micelles. The FTIR and 1H NMR spectral study observations

confirm the interaction between SDS and Q1/Q2 molecule leading to packing of Q1 or Q2

molecule within the micelle. All the studies were found in support of each other with respect

to the concentration range of micellization region.

Acknowledgement

Among authors V. Bhardwaj and P. Sharma are thankful to SAIF department, Panjab

University Chandigarh for providing FTIR and NMR study reports.

of 35

Accep

ted

Man

uscr

ipt

13

References

[1] S. Jantova, S. Stankovsky, K. Sporkova, In vitro antibacterial activity of ten series of

substituted quinazolines, Biologia Bratisalva. 59/6 (2004) 741-752.

[2] J. P. Michael, Quinoline, quinazoline and acridone alkaloids, Nat. Prod. Rep. 18 (2001)

543-559.

[3] D.E. Jane, K. Hoo, R. Kamboj, M. Deverill, D. Bleakman, Synthesis of willardiine and

6-azawillardiine analogs: Pharmacological characterization on cloned homomeric

human AMPA and kainite receptor subtypes, J. Med. Chem. 40 (1997) 3645-3650.

[4] V. Alagarsamy, V.R. Solomon, M. Murugan, Synthesis and pharmacological

investigation of novel 4-benzyl-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-

ones as new class of H1-antihistaminic agents, Bioorg. Med. Chem. 15 (2007) 4009-

4015.

[5] Z. Wang, M. Wang, X. Yao, Y. Li, J. Tan, L. Wang, W. Qiao, Y. Geng, Y. Liu, Q.

Wang, Design, synthesis and antiviral activity of novel quinazolinones, Eur. J. Med.

Chem. 53 (2012) 275-282.

[6] V. Bhardwaj, P. Sharma, M.N. Noolvi, H.M. Patel, S. Bansal, S. Lohan, G. Badola,

Certain 2-Furano-4(3H)-Quinazolinone Analogs: Synthesis, Characterization and

Pharmacological Evaluation, Letters in drug Design Dis. 10 (2013) 360-368.

[7] A. Mishra, K. Srivastava, R. Tripathi, S.K. Puri, S. Batra, Search for new

pharmacophores for antimalarial activity. Part III: Synthesis and bioevaluation of new

6-thioureido-4-anilinoquinazolines, Eur. J. Med. Chem. 44 (2009) 4404-4412.

of 35

Accep

ted

Man

uscr

ipt

14

[8] S. Mowafy, N.A. Farag, K.A.M. Abouzid, Design, synthesis and in vitro anti-

proliferative activity of 4,6-quinazolinediamines as potent EGFR-TK inhibitors, Eur. J.

Med. Chem. 61 (2013) 132-145.

[9] A.S. El-Azab, K.E.H. ElTahir, Design and synthesis of novel 7-aminoquinazoline

derivatives: Antitumor and anticonvulsant activities, Bioorg. Med. Chem. Lett. 22

(2012) 1879-1885.

[10] V. Jatav, P. Mishra, S. Kashaw, J.P. Stables, Synthesis and CNS depressant activity of

some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styrylquinazoline-4(3H)-ones,

Eur. J. Med. Chem. 43 (2008) 135-141.

[11] S. Chauhan, M.S. Chauhan, D. Kaushal, V. K. Syal, J. Jyoyi, Study of micellar behavior

of SDS and CTAB in queous media containing furosemide-A cardiovascular drug, J.

Solution Chem. 39 (2010) 622-638.

[12] M.J. Rosen, Surfactants and Interfacial Phenomena, Third ed. Wiley Interscience, New

York, USA, 2004.

[13] S.K. Mehta, S. Chaudhary, K.K. Bhasin, R. Kumar, M. Aratono, Conductometric and

spectroscopic studies of sodium dodecyl sulfate in aqueous media in the presence of

organic chalcogen, Colloids Surf. A: Physicochem. Eng. Asp. 304 (2007) 88-95.

[14] M.N. Noolvi, H.M. Patel, V. Bhardwaj, A. Chauhan, Synthesis and in-vitro anti-tumor

activity of substituted quinazoline and quinoxaline derivatives: Search for anticancer

agent, Eur. J. Med. Chem.46 (2011) 2327-2346.

of 35

Accep

ted

Man

uscr

ipt

15

[15] Varun Bhardwaj, Poonam Sharma, S. Chauhan, M. S. Chauhan. Thermodynamic, FTIR,

1H-NMR, and acoustic studies of butylated hydroxyanisole and sodium dodecyl sulfate

in ethanol, water rich and ethanol rich solutions, J. Mol. Liq. 180 (2013) 192-199.

[16] V. Bhardwaj, P. Sharma, S. Chauhan, Thermo-acoustic investigation in alcohol-water

mixtures: Impact of lipophilic antioxidant on anionic surfactant properties for potential

cosmeceutical application, Thermochim. Acta 566 (2013) 155-161.

[17] P. Sharma, S. Chauhan, V.K. Syal, M.S. Chauhan, studies of partial molar volumes of

some narcotic-analgesic drugs in aqueous-alcoholic mixtures at 25 °C, Int. J.

Thermophys. 29 (2008) 643-655.

[18] M. Arias, L. Garcia-Rio, J.C. Mejuto, P. Rodriguez-Dafonte, J. Simal-Gandara,

Influence of micelles on the basic degradation of carbofuran, J. Agri. Food Chem. 53

(2005) 7172-7178.

[19] M. Arias, M.S. Garcia-Falcon, L. Garcia-Rio, J.C. Mejuto, R. Rial-Otero, J. Simal-

Gandara, Binding constants of oxytetracycline to animal feed divalent cations, J. Food

Eng. 78 (2007) 69-73.

[20] M. Arias-Estevez, D. Fernandez-Gandara, M.S. Garcia-Falcon, L. Garcia-Rio, J. C.

Mejuto, J. Simal-Gandara, Sorption of polycyclic aromatic hydrocarbons to colloid

dispersions of humic substances in water, Bull. Environ. Contam. Toxicol. 79 (2007)

251-254.

[21] G. Astray, C. Gonzalez-Barreiro, J.C. Mejuto, R. Rial-Otero, J. Simal-Gandara, A

review on the use of cyclodextrins in foods, Food Hydrocolloids 23 (2009) 1631-1640.

of 35

Accep

ted

Man

uscr

ipt

16

[22] M. Arias-Estevez, E. Lopez-Periago, E. Martinez-Carballo, J. Simal-Gandara, J.C.

Mejuto, L. Garacia-Rio, The mobility and degradation of pesticides in soils and the

pollution of groundwater resources, Agric. Ecosyst. Environ. 123 (2008) 247-260.

[23] G. Astray, J.C. Mejuto, J. Morales, R. Rial-Otero, J. Simal-Gandara, Factors controlling

flavors binding constants to cyclodextrins and their applications in foods, Food Res. Int.

43 (2010) 1212-1218.

[24] A. Cid, J.C. Mejuto, P.G. Orellana. O. Lopez-Fernandez, R. Rial-Otero, J. Simal-

Gandara, Effects of ascorbic acid on the microstructure and properties of SDS micellar

aggregates for potential food applications, Food Res. Int. 50 (2013) 143-148.

[25] J.P. Marcolongo, M. Mirenda, Thermodynamics of sodium dodecyl sulfate (SDS)

micellization: An undergraduate laboratory experiment, J. Chem. Edu. 88 (2011) 629-

633.

[26] F. Jalali, A.S. Rad, Conductance study of the thermodynamics of micellization of 1-

hexadecylpyridinium bromide in mixed solvents containing dilute electrolyte solutions,

J. Iran. Chem. Soc. 5 (2008) 309-315.

[27] B. Kumar, D. Tikariha, K.K. Ghosh, P. Quagliotto, Effect of short chain length alcohols

on micellization behavior of cationic Gemini and monomeric surfactants, J. Mol. Liq.

172 (2012) 81-87.

[28] M. Alauddin, N.P. Rao, R.E. Verrall, Apparent molar volume, apparent molar adiabatic

compressibility, and solubilization studies of aqueous solutions of sodium p-(n-

dodecyl)benzenesulfonate as a function of surfactant and solubilizate concentrations

and temperature, J. Phys. Chem. 92 (1988) 1301-1307.

of 35

Accep

ted

Man

uscr

ipt

17

[29] V.K. Syal, S. Chauhan, P.K. Gupta, P. Sharma, Physicochemical studies of some

bivalent electrolytes in aqueous mixtures of DMSO at different temperatures by

transport property measurements, Electrochem. Soc. Ind. 1 (2004) 53-57.

[30] J. Krzaczkowska, E. Scczesniak, S. Jurga, Phase behavior of

dipalmitoylphosphatidylcholine/surfactant/water systems studied by infrared

spectroscopy, J. Mol. Struct. 794 (2006) 168-172.

[31] S. P. Mulye, S. A. Jamadar, P. S. Karekar, Y. V. Pore, S. C. Dhawale, Improvement in

physicochemical properties of ezetimibe using a crystal engineering technique, Powder

Technol. 222 (2012) 131-140.

[32] T. Farias, L. C. De-Menorval, J. Zajac, A. Rivera, Solubilization of drugs by cationic

surfactants micelles: Conductivity and 1H NMR experiments, Colloids Surf. A:

Physicochem. Eng. Asp. 345 (2009) 51-57.

of 35

Accep

ted

Man

uscr

ipt

18

Figure Captions

Fig. 1. Specific conductivity plot of SDS at different temperatures containing Q2 in 43.36

weight (%) ethanol + water mixture.

Fig. 2. The variation of ΔG°m, ΔH°

m and ΔS°m with regard to Q1 and Q2 at different

temperatures.

Fig. 3. Apparent molar volume (φv) versus SDS 43.36 weight (%) ethanol + water mixture

containing Q1 at different temperatures.

Fig. 4. Apparent molar volume (φv) versus SDS in 43.36 weight (%) ethanol + water mixture

containing Q2 at different temperatures.

Fig. 5. FTIR spectrum representing (a) SDS, (b) SDS in presence of Q1 and (c) SDS in presence of Q2.

Fig. 6. NMR spectrum of (a) SDS, (b) SDS in presence of Q1 and (c) SDS in presence of Q2.

Fig. 7. Hypothetical model representing the location of Q1 and Q2.

of 35

Accep

ted

Man

uscr

ipt

19

List of Tables

Table 1 CMC, Xcmc, α, ΔH°m, ΔG°

m, and ΔS°m values of SDS in 43.36 weight (%) ethanol +

water mixture at 25, 30 and 35 °C containing Q1 and Q2 at three different temperatures.

Table 2 Density (ρ) (kgm-3), ultrasonic velocity (u) (ms-1) and compressibility coefficient (β)

(TPa-1) of SDS (0.002-0.014 mol kg-1) in 43.36 weight (%) ethanol + water mixture at 25, 30

and 35 °C.

Table 3 Apparent molar volume (φv) (m3mol-1), and apparent molar compressibility (φk)

(m3mol-1TPa-1) of SDS in 43.36 weight (%) ethanol + water mixture at 25, 30 and 35 °C.

of 35

Accep

ted

Man

uscr

ipt

20

Table 1 CMC, Xcmc, α, ΔH°m, ΔG°

m, and ΔS°m values of SDS in 43.36 weight (%) ethanol +

water mixture at 25, 30 and 35 °C containing Q1 and Q2 at three different temperatures.

Compounds T °C CMC (103)

Xcmc (103) α ΔH°

m (kJ mol-1)

ΔG°m

(kJ mol-1) ΔS°

m (J mol-1 K-1)

25 7.4 9.9 0.61 -7.77 -15.86 27.14

30 7.6 10.1 0.64 -7.92 -15.85 26.18

35 7.9 10.5 0.66 -8.04 -15.64 24.65

25 5.8 7.7 0.51 -8.37 -18.00 32.32

30 6.1 8.1 0.52 -8.58 -17.88 30.71

35 6.4 8.6 0.54 -8.73 -17.75 29.28

of 35

Accep

ted

Man

uscr

ipt

21

Table 2 Density (ρ) (kgm-3), ultrasonic velocity (u) (ms-1) and compressibility coefficient (β)

(TPa-1) of SDS (0.002-0.014 mol kg-1) in 43.36 weight (%) ethanol + water mixture at 25, 30

and 35 °C.

Q1 (0.01 mol Kg-1) Q2 (0.02 mol Kg-1) [SDS] mol Kg-1 25 °C 30 °C 35 °C 25 °C 30 °C 35 °C ρ (kgm-3)

0.002 873.293 862.642 859.094 842.935 838.932 829.502 0.004 873.183 862.864 859.392 843.420 838.975 829.483 0.006 874.464 863.752 859.889 843.494 838.892 829.290 0.008 874.321 863.621 859.878 843.074 838.754 829.234 0.010 874.102 863.498 859.724 842.281 838.201 829.134 0.012 874.092 863.435 859.489 841.821 838.189 829.178 0.014 874.001 863.378 859.302 841.835 838.105 829.134

u (ms-1) 0.002 1422.34 1411.13 1389.54 1382.67 1375.43 1370.89 0.004 1421.56 1410.38 1388.84 1382.23 1375.38 1370.81 0.006 1419.43 1409.89 1387.43 1382.02 1375.21 1370.72 0.008 1418.55 1409.01 1386.45 1381.93 1375.18 1370.67 0.010 1416.06 1408.34 1385.32 1381.84 1375.11 1370.60 0.012 1415.63 1407.34 1384.98 1381.88 1375.02 1370.53 0.014 1415.39 1406.45 1384.09 1381.82 1375.00 1370.46

β (TPa-1) × 10-10 0.002 5.660 5.822 6.029 6.205 6.301 6.415 0.004 5.667 5.826 6.033 6.206 6.300 6.416 0.006 5.676 5.824 6.041 6.207 6.303 6.418 0.008 5.684 5.832 6.049 6.211 6.304 6.419 0.010 5.705 5.838 6.061 6.217 6.309 6.420 0.012 5.709 5.847 6.066 6.220 6.310 6.421 0.014 5.711 5.855 6.075 6.221 6.311 6.422

of 35

Accep

ted

Man

uscr

ipt

22

Table 3 Apparent molar volume (φv) (m3mol-1), and apparent molar compressibility (φk)

(m3mol-1TPa-1) of SDS in 43.36 weight (%) ethanol + water mixture at 25, 30 and 35 °C.

Q1 (0.01 mol Kg-1) Q2 (0.02 mol Kg-1) [SDS] mol Kg-1 25 °C 30 °C 35 °C 25 °C 30 °C 35 °C

φv (m3mol-1) 0.002 0.00434 0.00347 0.00295 0.00242 0.00198 0.00175 0.004 0.00246 0.00183 0.00154 0.00129 0.00115 0.00105 0.006 0.00149 0.00113 0.00103 0.00099 0.00089 0.00087 0.008 0.00125 0.00095 0.00085 0.00093 0.00078 0.00075 0.010 0.00111 0.00085 0.00077 0.00094 0.00077 0.00068 0.012 0.00099 0.00076 0.00073 0.00091 0.00070 0.00062 0.014 0.00092 0.00071 0.00068 0.00084 0.00066 0.00058

φk (m3mol-1TPa-1) 0.002 2.4565 2.01739 1.77883 1.4983 1.2493 1.1212 0.004 1.39332 1.06327 0.93018 0.8055 0.7232 0.6765 0.006 0.85023 0.65755 0.62067 0.6157 0.5668 0.5555 0.008 0.71111 0.55531 0.51795 0.5752 0.4948 0.4789 0.010 0.63501 0.49326 0.46838 0.5840 0.4892 0.4372 0.012 0.56979 0.44836 0.44061 0.5656 0.4448 0.3981 0.014 0.52752 0.41593 0.41834 0.5224 0.4177 0.3761

of 35

Accep

ted

Man

uscr

ipt

Graphical Abstract

Graphical Abstract (for review)

of 35

Accep

ted

Man

uscr

ipt

Fig. 1.

Figure(s)

of 35

Accep

ted

Man

uscr

ipt

Fig. 2.

Figure(s)

of 35

Accep

ted

Man

uscr

ipt

Fig. 3.

Figure(s)

of 35

Accep

ted

Man

uscr

ipt

Fig. 4.

Figure(s)

of 35

Accep

ted

Man

uscr

ipt

(a)

Figure(s)

of 35

Accep

ted

Man

uscr

ipt

(b)

of 35

Accep

ted

Man

uscr

ipt

(c)

Fig. 5(a,b,c).

of 35

Accep

ted

Man

uscr

ipt

(a)

Figure(s)

of 35

Accep

ted

Man

uscr

ipt

(b)

of 35

Accep

ted

Man

uscr

ipt

(c)

Figure 6(a,b,c).

of 35

Accep

ted

Man

uscr

ipt

Fig. 7.

Figure(s)

of 35

Accep

ted

Man

uscr

ipt

In this study, interaction of two synthesized analogs and SDS has been examined.

Thermo-acoustic parameters were calculated from density and ultrasonic sound velocity data.

Existence of hydrophobic and electrostatic forces was observed.

Spectroscopic study provided the locus of molecules within micellar structure.

*Highlights (for review)

thermo-physical examination: synthesized 2-furano-4(3h)-quinazolinone and open quinazolinone...

Documents