New Urea-Based Surfactants Derived from r,ω-Amino Acids

Celia M. C. Faustino,*,† Antonio R. T. Calado,† and Luıs Garcia-Rio‡

iMed.UL, Faculty of Pharmacy, UniVersity of Lisbon, AV. Prof. Gama Pinto, 1649-003 Lisboa, Portugal, andPhysical Chemistry Department, Faculty of Chemistry, UniVersity of Santiago de Compostela,15782-Santiago de Compostela, Spain

ReceiVed: August 18, 2008; ReVised Manuscript ReceiVed: NoVember 18, 2008

New anionic urea-based surfactants derived from R,ω-amino acids and in particular from �-alanine weresynthesized and their solution properties characterized by electrical conductivity, equilibrium surface tension,and steady-state fluorescence spectroscopy techniques. Double-chain surfactants and the single-chain surfactantcontaining a sulfate head group exhibited the lowest critical micelle concentration (cmc) values and superiorefficiency in lowering surface tension. All surfactants promoted adsorption relative to micellization, and micellarparameters were sensitive to the hydrophobicity of the amino acid residue. The polarity of the interfacialregion, measured with the solvatochromic probe ET(30) (Reichardt’s betaine dye), was similar to sodiumdodecyl sulfate (SDS) micelles.

Introduction

Surface active agents (surfactants) are characterized by thepresence of both hydrophilic and hydrophobic regions in thesame molecule. The amphipathic nature of these compounds isresponsible for their unique properties, such as adsorption atinterfaces, self-association, and solubilization, among others.1,2

Surfactant solutions are characterized by a sudden transitionin their physical properties over a narrow range of concentra-tions, called critical micelle concentration (cmc). The transitionis due to the formation of supramolecular assemblies known asmicelles.1,2

Surfactants are widely used in the food, pharmaceutical,cosmetic, textile, paint, and coating industries as emulsifyingagents, solubilizers, suspension stabilizers, and wetting andfoaming agents. Much attention has been focused on theirsolubilization properties and on their use as drug delivery agents,templates for nanoparticles, models for biomembranes, andreaction media.1,2

The demand for both better and environmentally friendlysurfactants leads to the growing need for new surfactants withimproved performance and lower toxicity.3-9

In this paper we report the synthesis and characterization ofnew urea-based surfactants derived from the amino acid�-alanine. Amino acid surfactants have received much attentionbecause of their good biodegradability and biocompatibility.5-9

�-Alanine and other terminal R,ω-amino acids were chosen toavoid introduction of chiral centers while the urea moiety mayplay an important role in tuning the properties by means ofhydrogen bonding.10a The lyotropic phase behavior of urea-basedsurfactants has been studied by the group of Drummond.10b-d

Both the amino acid and the urea functions offer the additionaladvantage of potential biological activity, namely antibacterialand/or antifungal.6,9,11,12

Experimental Methods

Materials. The amino acids glycine, �-alanine, 5-aminova-leric acid, 2-aminoethyl hydrogen sulfate, and 2-aminoethyl

dihydrogen phosphate and the amines dioctylamine and bis(2-ethylhexyl)amine were purchased from Aldrich while γ-ami-nobutyric acid, 6-aminohexanoic acid, and taurine were obtainedfrom Sigma. Octyl isocyanate and ethyl 3-isocyanatopropanoatewere also from Aldrich. All the compounds were of the highestcommercially available purity and were used as received.

Synthesis. The single-chain surfactants 2 were synthesizedby the condensation reaction of octyl isocyanate and thecorresponding amino acid compound (Scheme 1) according tomethods described in the literature.13,14 In a typical reaction aquantity corresponding to 0.01 mol of the amino acid 1 wasdissolved in 10 mL (20 mL in the case of 1h) of aqueous sodiumhydroxide with a concentration of 1 mol dm-3. After stirringfor 1 h at room temperature, a solution obtained by dissolving1.8 mL (0.01 mol) of octyl isocyanate in 10 mL of acetonewas added dropwise, and the reaction mixture was left overnight.After 24 h a white solid precipitated, which was collected byfiltration and recrystallized from a mixture of water/acetone.

The double-chain surfactants 3 were obtained by the con-densation of stoichiometric amounts of ethyl 3-isocyanatopro-panoate with the corresponding disubstituted amine dissolvedin dichloromethane and subsequent alkaline hydrolysis of theintermediate ethyl ester (Scheme 2). The reaction mixture wasevaporated under reduced pressure, and the surfactants wereobtained as pale yellow gels. The compounds were purified byrecrystallization from a mixture of water and acetone.

All the compounds were characterized by 1H and 13C NMRspectroscopy and FT-IR spectroscopy. 1H and 13C NMR spectrawere measured in D2O on a Bruker Avance ARX-400 spec-trometer operating at 400 and 100 MHz, respectively. The 1HNMR spectra obtained all showed the sharp peak of HOD at4.70 ppm. IR spectra, in KBr pellets, were obtained with aNicolet Impact 400 FT-IR spectrophotometer. Melting points(uncorrected) were obtained with a Mettler FP5 capillary meltingpoint apparatus and were confirmed in a Kopler Bock-Monoscopapparatus. Full details of the physicochemical and spectroscopiccharacterization of the synthesized surfactants are given in theSupporting Information.

Conductance Measurements. Conductivity data were col-lected at 25 °C and 1 kHz with a Wayne-Kerr B905 automaticprecision bridge (WKR, England) using a Ingold conductivity

* Corresponding author: Ph (351) 214 946 400; Fax (351) 217 946 470;e-mail cfaustino@ff.ul.pt.

† University of Lisbon.‡ University of Santiago de Compostela.

J. Phys. Chem. B 2009, 113, 977–982 977

10.1021/jp807396k CCC: $40.75 2009 American Chemical SocietyPublished on Web 01/06/2009

cell type 980-K19/120 with platinum electrodes and a cellconstant of 1.004 cm-1, according to literature procedures.15-18

The cell was calibrated using standard Crison KCl solutions ofthe appropriate concentration range.

All solutions were prepared with double-distilled deionizedwater (Milli-Q water purification system) yielding values alwayslower than 1 µS cm-1. The pH of the surfactant solutions wasbetween 6.5 and 7.0.

ET(30) Values. The solvatochromic probe 2,6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio)phenoxide, also known as Rei-chardt’s betaine dye, was obtained from Sigma and used asreceived.

UV-vis absorbance spectra were recorded on a UV-visShimadzu UV-1603 spectrophotometer equipped with a ther-mostated cell compartment. All measurements were made at25.0 °C using quartz absorption cells with a path length of 1.0cm.

Surfactant solutions of concentration at least twice their cmcwere prepared in 10-3 mol dm-3 sodium hydroxide to ensurethe presence of the zwitterionic form of the dye, which is theactive species. Each surfactant solution contained a finalconcentration of betaine dye equal to 2 × 10-4 mol dm-3.Identical solutions without the probe molecule were used asblanks.

Fluorescence Quenching Measurements. The fluorescentmeasurements were performed using a Hitachi F-2000 fluores-cence spectrophotometer. Pyrene was used as the fluorescentprobe, with a concentration of 2 × 10-6 mol dm-3 for eachsurfactant solution. Cetylpyridinium chloride was used as thequencher, in increasing concentrations, varying from 0 up to 5× 10-4 mol dm-3. An excitation wavelength of 335 nm wasused, and readings were made at the emission wavelength of384 nm, corresponding to the third vibronic peak of pyrene.All surfactant solutions had fixed surfactant concentration atleast twice the value of its cmc.

Surface Tension Measurements. Surface tensions wereobtained by the Wilhelmy plate technique, using a Kruss K12tensiometer. The glass vessel was cleaned with chromic mixture,rinsed repeatedly with water, and dried prior to use. Theplatinum plate was washed with water and acetone and flame-dried before each measurement. Sets of measurements weretaken until the change in surface tension was less than 0.05mN m-1 every 5 min. The equilibrium surface tension wasdetermined from the last 10 values obeying the former condition.Surfactant solutions of concentration above the cmc reachedequilibrium within 2-3 h, whereas those below the cmc requiredup to 8 h to stabilize.

The surface tension vs logarithm of surfactant concentrationplots for the compounds studied showed no minimum, whichis a good indication of purity.

Antimicrobial Activity. The antimicrobial activities of thesurfactants synthesized were evaluated in vitro against thefollowing micro-organisms: E. coli (ATCC 25922), P. aerugi-nosa (ATCC 27853), S. aereus (CIP 106760), M. smegmatis(ATCC 607), and C. albicans (ATCC 10231).

Results and Discussion

Conductivity Data. All the urea surfactants synthesizedshowed good water solubility up to concentrations of 0.20 moldm-3, a factor that can be attributed to the anionic amino acidresidue, as nonionic urea surfactants are known to be highlyinsoluble in aqueous media.19,20

The cmc of the surfactants was taken as the concentration atthe intersection of the linear portions of the conductivity vsconcentration plots above and below the break point, accordingto the Williams method,21 as shown in Figure 1 for surfactants2a-e. As expected, the slope above the cmc is lower than theone below the cmc, as micelles are worse charge carriers whencompared to the surfactant monomers.

The average degree of micellar ionization, R, was taken asthe ratio of the slopes above and below the cmc in the electricalconductivity vs concentration plots. Its difference from unitycorresponds to the degree of counterion binding, �, to themicelle/solution interface (� ) 1 - R).

According to the mass action model, which works well forionic micelles, the standard Gibbs energy of micellization, ∆GM

° ,per mole of hydrocarbon chain, was calculated using eq 1,proposed by Zana22 for single-chain (j ) 1) and double-chain(j ) 2) surfactants with monovalent counterions:

where j is the number of hydrocarbon chains of the surfactantmolecule, R is the gas constant (8.314 J mol-1 K-1), and T isabsolute temperature.

The micellar parameters obtained from conductivity data areshown in Table 1.

The cmc of ionic surfactants usually decreases with increasingnumber of carbon atoms in the hydrophobic side chain up to ahexadecyl group, being less influenced by the number of carbonatoms of the chain attached to the polar group.9,23 In this worka correlation was obtained between the cmc and the amino acidresidue, the cmc being lower the more hydrophobic the latter,although the effect is much less pronounced when comparedwith the one observed for the hydrophobic side chain. Figure 2shows the relationship between the logarithm of the cmc andthe number of carbon atoms in the side chain of the amino acidresidue, which is analogous to the one observed for the logarithmof the cmc and the number of carbon atoms of the hydrophobicchain for homologous straight-chain ionic surfactants:

where A and B are constants and nC is the number of carbonatoms of the hydrocarbon chain. The parameters obtained wereA ) -0.051 and B ) 0.997, with a correlation coefficient of0.94.

There seems to be an odd-even effect in the micellarparameters for the homologous anionic urea surfactants 2a-e

SCHEME 1

∆GM◦ ) (1/j){RT(1 + �) ln cmc + RT[� ln(1/j) - ln j]}

(1)

log cmc ) A - BnC (2)

978 J. Phys. Chem. B, Vol. 113, No. 4, 2009 Faustino et al.

as the cmc, the degree of counterion binding � to the micelle,and the values of ∆GM

° all decrease with increase in the numberof carbon atoms for compounds 2a, 2c, and 2e, with evennumber of carbon atoms in the amino acid residue, and for theodd-numbered compounds 2b and 2d. A similar trend isobserved in the melting points of the compounds, which increasewith increase in the number of carbon atoms of the amino acidresidue up to five carbon atoms (compound 2d), which has alower melting point than the others.

The cmc values of these surfactants are much closer to thecmc of sodium decanoate (1.09 × 10-1 mol dm-3)24 andtrimethyldecylammonium bromide (6.7 × 10-2 mol dm-3),25

surfactants with 10 carbon atoms in their alkyl chains, than with

the octyl hydrocarbon chain surfactant sodium octanoate (3.5× 10-1 mol dm-3).24 Cmc values in the millimolar range havebeen obtained for the sodium salts of N-dodecanoylamino acidsderived from �-alanine,26 glycine,27 and alanine23,27 while a valueof 1.5 × 10-2 mol dm-3 has been reported for N-dodecanoylsarcosinate.28 Dodecanoyl and decanoyl surfactants obtainedfrom N-acylation of leucine27 have cmc values of 9.2 × 10-4

and 2.0 × 10-3 mol dm-3, respectively. Cmc values of the order10-2 mol dm-3 can thus be expected for N-octanoyl derivatives,which is the case for the compounds studied.

The values of ∆GM° per hydrocarbon chain of the double-

chain surfactants 3a,b are smaller than the corresponding single-chain surfactant 2b, an indication that it is more difficult forthe double-chain surfactants to form micelles, probably due tosteric hindrance by closely connected hydrocarbon chains,26

which is more obvious in the branched surfactant.The cmc for surfactant 3b is about 10 times greater than the

values reported in the literature for sodium bis(2-ethylhexyl)phosphate (1.5 × 10-3 mol dm-3)29 and sodium bis(2-ethyl-hexyl) sulfosuccinate, AOT (2.72 × 10-3 mol dm-3),29,30

surfactants with the same branched alkyl chained structure,which can be attributed to the difference in polarity of thedistinct head groups.

The cmc of the surfactants obtained by substitution of thecarboxylate group of the �-alanine residue (2b) with sulfonate(2f), sulfate (2g), and phosphate (2h) groups decreases slightly,in the order

CO2- > OPO3

2- > SO3- > OSO3

-

Thus, surfactants containing sulfur and phosphorus atoms in theirpolar head groups seem to be more prone to micellization thancarboxylate surfactants due to the higher polarizability of theformer.

Again, the cmc values obtained are closer to the correspond-ing decyl chain surfactants (2.1 × 10-2 mol dm-3 for sodiumdecylsulfonate and 3.3 × 10-2 mol dm-3 for sodium decylsulfate)30 than with the octyl chained ones (1.5 × 10-1 mol dm-3

for sodium octylsulfonate and 1.33 × 10-1 mol dm-3 for sodiumoctyl sulfate).30

ET(30) Values. The Reichardt’s betaine dye ET(30) has beenused to characterize the polarity of the interfacial region. Thisprobe molecule is known to solubilize in the aqueous interface,31

thus providing information about changes in polarity caused,for example, by variations in the surfactant structure.

The medium polarity was calculated from the wavelengthmaximum of the lowest energy intramolecular charge-transferπ-π* absorption band of the probe, according to eq 3:31

The results obtained are presented in Table 1. All surfactantsshow similar values to the ones obtained for alcohols (55.4 formethanol and 57.0 for glycerol).31 The values agree well withthe ones of 57.5 and 56.7 reported in the literature31 for SDSand sodium dodecanoate micelles, respectively. The surfactants2f-h containing head groups with heteroatoms instead of

Figure 1. Variation of conductivity with surfactant concentration forsurfactants 2a-e.

Figure 2. Variation of the logarithm of the cmc with the number ofcarbon atoms for single-chain surfactants with carboxylate head groups2a-e.

TABLE 1: Critical Micelle Concentration (cmc), Degree ofCounterion Binding (�), and Standard Gibbs Energy ofMicellization (∆GM

° ) Obtained from ConductivityMeasurements, and Polarity of the Interface Region (ET(30)Values)

compound102 cmc/mol

dm-3 �∆GM

° /kJmol-1

ET(30)/kcalmol-1

2a 7.64 0.43 -9.09 56.32b 7.21 0.37 -8.90 56.32c 6.48 0.34 -9.12 56.32d 5.91 0.29 -9.04 55.72e 4.69 0.33 -10.07 55.72f 6.63 0.42 -9.57 57.22g 5.72 0.34 -9.48 58.52h 6.87 0.35 -11.33 58.03a 3.04 0.62 -7.87 56.13b 2.32 0.15 -6.21 56.3

SCHEME 2

ET(30)/kcal mol-1 ) 28591.5/(λmax/nm) (3)

Urea-Based Surfactants J. Phys. Chem. B, Vol. 113, No. 4, 2009 979

carboxylate have higher ET(30) values, indicating a more polarinterface region.

Fluorescence Quenching Data. The aggregation number ofthe surfactants studied was determined by a steady-statefluorescence quenching method, using pyrene as the fluorescentprobe and cetylpyridinium chloride as the quencher. Theaggregation number, N, for surfactant solutions of constantconcentration twice the cmc, and increasing concentration ofquencher, was obtained from the slope of the straight lineobtained by plotting ln(I0/I) vs quencher concentration, accordingto the equation

where I and I0 are the fluorescence intensities with and withoutquencher, and [Q] and [S] are quencher and surfactant concen-trations, respectively. The results obtained are summarized inTable 2 and will be dealt with in the next section.

Surface Tension Data. From surface tension measurementsthe cmc and the surface tension at the cmc were determinedfrom the break point in the surface tension vs logarithm ofsurfactant concentration profile, as exemplified in Figure 3 forsurfactants 2b and 2f-h.

The maximum surface excess concentration at the air/solutioninterface, corresponding to the saturation adsorption value, Γmax,was determined using the Gibbs adsorption isotherm:

where γ is the surface tension in N m-1, R is the gas constant(8.314 J mol-1 K-1), T is absolute temperature, c is surfactantconcentration in mol dm-3, and (∂γ/∂ log c) is the slope belowthe cmc in the surface tension vs logarithm of surfactantconcentration plots. The value of i, the number of (ionic) specieswhose concentration at the interface changes with the surfactantconcentration, is thus 2.

The minimum area occupied per surfactant molecule at theair/solution interface, Amin, was obtained from the saturatedadsorption value, Γmax, as

where NA is Avogadro’s number and Amin is in m2.The Gibbs energy of adsorption at the air/solution interface,

∆Gads° , was calculated from

where πcmc represents the surface pressure at the cmc, in mNm-1, according to eq 8:

The last equation was used to determine the ratio cmc/c20, c20

being the concentration required to lower the surface tensionof water, γ0, by 20 mN m-1. From this ratio pc20 (negative logc20) values were obtained. Micellar parameters obtained fromsurface tension measurements are summarized in Table 2.

The cmc values obtained from surface tension values areslightly lower than the ones obtained from conductivity mea-surements; however, they agree well. These systematic differ-ences may be related with specificities of the methods sincesurface tension measurements are sensitive mainly to theconcentration of the monomeric form of the surfactant, asmicelles are not surface active, while electric conductivitymethods depend on the conductivity of all the ionic speciespresent.

The surface tensions at the cmc of the double-chain surfac-tants are lower than those of the single-chain surfactants, andthe former adsorb strongly at the air/solution interface whichcan be attributed to strong hydrophobic interactions betweenmultiple hydrocarbon chains.

TABLE 2: Critical Micelle Concentration (cmc), Surface Tension at cmc (γcmc), pc20, cmc/c20, Saturation Adsorption (Γmax),Area Occupied per Surfactant Molecule at the Air/Water Interface (Amin), Standard Gibbs Adsorption Energy (∆Gads

° ), andAggregation Number (N)

compound 102 cmc/mol dm-3 γcmc/mN m-1 pc20 cmc/c20 106Γmax/mol m-2 1018Amin/m2 ∆Gads° /kJ mol-1 Na

2a 7.62 41.20 1.6 3.2 1.89 0.88 -25.41 422b 7.19 39.20 1.9 5.9 1.46 1.14 -31.37 452c 6.37 35.89 2.2 10.7 1.37 1.21 -35.50 482d 5.79 43.75 1.8 3.7 1.26 1.31 -31.38 512e 4.60 37.02 2.4 11.0 1.26 1.32 -37.80 532f 6.50 37.00 2.0 6.3 1.65 1.01 -30.83 462g 5.70 24.85 3.0 51.8 1.39 1.20 -43.47 432h 6.81 36.26 2.1 9.4 0.94 1.76 -49.22 423a 2.80 25.27 8.5 1 × 107 0.34 4.92 -146.4 233b 2.24 28.50 5.9 2 × 104 0.49 3.40 -95.30 26

a From fluorescence measurements.

Figure 3. Variation of surface tension with logarithm of surfactantconcentration for surfactants 2b and 2f-h.

ln(I0

I ) ) N[Q][S] - cmc

(4)

Γmax ) - 12303iRT( ∂γ

∂ log c)T(5)

Amin ) 1NAΓmax

(6)

∆Gads◦ ) ∆GM

◦ -πcmc

Γmax(7)

πcmc ) γ0 - γcmc ) 20 + iRTΓmax lncmcc20

(8)

980 J. Phys. Chem. B, Vol. 113, No. 4, 2009 Faustino et al.

Surface tensions at the cmc for the single-chain surfactantsderived from �-alanine by substitution of the carboxylate group(2b) with sulfonate (2f) and phosphate (2h) groups do not differsignificantly, while substitution with a sulfate head group (2g)decreases the γcmc in a way comparable to the introduction ofa second hydrocarbon chain.

The saturation adsorption values, Γmax, decrease with increas-ing hydrophobicity of the amino acid residue, for the homo-logues series 2a-e, reaching a constant value for a number ofcarbon atoms g5. The inverse is true for the minimum areaoccupied per surfactant molecule, Amin, according to increasingmicelle size. Double-chain surfactants show lower Γmax andhigher Amin as the introduction of a second hydrocarbon chainmakes packing at the monolayer more difficult. The fact thatboth cmc and Amin are lower for the branched double-chainsurfactant 3b when compared to the analogous surfactant 3awith two linear hydrocarbon chains suggests that packing forthe branched surfactant, in micelles as well as in the monolayer,is favored probably due to adoption of a spherical shape. Amore favorable packing is also supported by the increase inaggregation number observed for the branched surfactant. Asimilar trend has been reported in the literature for �-branchedmicelles.32,33

Surfactants with sulfonate (2f) and sulfate (2g) head groupshave Amin comparable to the one with carboxylate head group(2b) while for the phosphate surfactant (2h) Amin is superiordue to the increase in electrostatic repulsions resulting fromdissociation of the dianion.

The efficiency of adsorption of a surfactant at the air/waterinterface can be characterized by pc20, the negative logarithmof the surfactant concentration c20 at which the surface tensionof water is reduced by 20 mN m-1.

The larger the pc20, the greater the tendency of the surfactantto adsorb at the air/water interface relative to its tendency toform micelles and the more efficiently it reduces the surfacetension. This trend can be seen in the substitution of thecarboxylate group of the �-alanine residue with sulfonate,sulfate, and phosphate groups, where pc20 increases in decreasingorder of cmc.

For single-chain surfactants with carboxylate head groups(2a-e) the pc20 values increase in the order of increasing numberof carbon atoms of the amino acid residue (except for 2d),suggesting that the more hydrophobic the amino acid residue,the stronger the adsorption at the air/solution interface.

Double-chain surfactants show the highest pc20 values dueto the presence of two hydrocarbon chains. The branchedsurfactant shows a lower value compared to the linear one dueto the more difficult packing of the branched chains in themicelles as well as in the monolayer.

The cmc/c20 ratio is a measure of the effectiveness of asurfactant, which can be correlated with structural factors onthe micellization and adsorption processes. Again, the largerthe ratio, the greater the tendency of the surfactant to adsorbat the interface relative to its tendency to form micelles. Thevalues obtained follow the same trend observed for the c20

values.For all the surfactants studied, the -∆GM

° values are smallerthan the values of -∆Gads

° , an indication that adsorption ispromoted much more than micellization, so that a significantamount of work has to be done to transport the surfactantmolecules from the surface to the micelle through the aqueousmedium. This result is supported by the large pc20 and cmc/c20

values. Therefore, anionic urea-based surfactants derived from�-alanine are more likely than other amino acid-based surfac-

tants to adsorb at the air/water interface rather than to formmicelles, a factor that can be attributed to the urea moiety.

The absolute values of both ∆GM° and ∆Gads

° increase withincreasing hydrocarbon chain length of the surfactant (exceptfor 2d), suggesting that a driving force of micellization oradsorption is derived from the hydrophobic amino acid residuesdue to the interaction between the hydrophobic moieties andthe hydrocarbon chains.

The odd-even effect is not evident from surface tension data,as only 2d deviates from the homologous series 2a-e, and thusneeds to be clarified in future studies.

Antimicrobial Activity. The surfactants studied lackedantimicrobial activity which can be due to their short alkyl chain,as the compounds with antimicrobial properties described inthe literature usually have alkyl chain lengths of more than 10carbon atoms.6,9,11,12,34 Optimum antimicrobial activity has beenreported for surfactants with alkyl chain lengths of 12 carbonatoms.34 However, maximum activity was found for argininediglycerides35 with alkyl chains of eigth carbon atoms. On thecontrary, dialkyl surfactants 3 did not show biological activitywhich can be atributed to the anionic nature of their polar headgroups, as the arginine diglycerides are cationic surfactants.

Conclusions

Anionic urea-based surfactants derived from R,ω-amino acidsshow cmc’s in the order 10-2 mol dm-3 and a high efficiencyin lowering surface tension, especially the double-chain sur-factants and the single-chain surfactant with the sulfate headgroup. These surfactants are more likely to adsorb at the air/water interface rather than to form micelles.

Acknowledgment. The authors thank Prof. Aida Duarte andDr. Alexandra Silva, from iMed.UL, Faculty of Pharmacy,University of Lisbon, for the antimicrobial screening assays.

Supporting Information Available: Full details of thephysicochemical and spectroscopic characterization of thesynthesized surfactants. This material is available free of chargevia the Internet at http://pubs.acs.org.

References and Notes

(1) Attwood, D.; Florence, A. T. Surfactant Systems. Their Chemistry,Pharmacy and Biology; Chapman and Hall: London, 1983.

(2) Fendler, J. H. Membrane Mimetic Chemistry. Characterizations andApplications of Micelles. Microemulsions, Monolayers, Bilayers, Vesicles,Host-Guest Systems, and Polyions; John Wiley & Sons: New York, 1982.

(3) Holmberg, K. Curr. Opin. Colloid Interface Sci. 2001, 6, 148–159.

(4) Chevalier, Y. Curr. Opin. Colloid Interface Sci. 2002, 7, 3–11.(5) Infante, M. R.; Pinazo, A.; Seguer, J. Colloids Surf., A 1997, 123-

124, 49–70.(6) Infante, M. R.; Perez, L.; Pinazo, A.; Clapes, P.; Moran, M. C.;

Angelet, M.; Garcia, M. T.; Vinardell, M. P. C. R. Chimie 2004, 7, 583–592.

(7) Moran, M. C.; Pinazo, A.; Perez, L.; Clapes, P.; Angelet, M.; Garcia,M. T.; Vinardell, M. P.; Infante, M. R. Green Chem. 2004, 6, 233–240.

(8) Xia, J.; Qian, J.; Nnanna, I. A. J. Agric. Food Chem. 1996, 44,975–979.

(9) Xia, J.; Xia, Y.; Nnanna, I. A. J. Agric. Food Chem. 1995, 43,867–871.

(10) (a) Fong, C.; Wells, D.; Krodkiewska, I.; Hartley, P. G.; Drummond,C. J. Chem. Mater. 2006, 18, 594–597. (b) Wells, D.; Fong, C.; Krodk-iewska, I.; Drummond, C. J. J. Phys. Chem. B 2006, 110, 5112–5119. (c)Wells, D.; Fong, C.; Drummond, C. J. J. Phys. Chem. B 2006, 110, 12660–12665. (d) Fong, C.; Wells, D.; Krodkiewska, I.; Weerwardeena, A.; Booth,J.; Hartley, P. G.; Drummond, C. J. J. Phys. Chem. B 2007, 111, 10713–10722.

(11) Kim, I.-H.; Morisseau, C.; Watanabe, T.; Hammock, B. D. J. Med.Chem. 2004, 47, 2110–2122.

(12) McElroy, N. R.; Jurs, P. C.; Morisseau, C.; Hammock, B. D. J. Med.Chem. 2003, 46, 1066–1080.

Urea-Based Surfactants J. Phys. Chem. B, Vol. 113, No. 4, 2009 981

(13) Vishnyakova, T. P.; Gouleva, I. A.; Glebova, E. V. Russ. Chem.ReV. 1985, 54, 429–449.

(14) Groszek, G. Org. Process. Res. DeV. 2002, 6, 759–761.(15) Alfaia, A. J. I.; Calado, A. R. T.; Reis, J. C. R. Eur. J. Org. Chem.

2000, 3627–3631.(16) Pinheiro, L. M. V.; Calado, A. R. T.; Reis, J. C. R. Org. Biomol.

Chem. 2004, 2, 1330–1338.(17) Garcia-Rio, L.; Herves, P.; Leis, J. R.; Mejuto, J. C.; Rodriguez-

Dafonte, P. J. Phys. Org. Chem. 2004, 17, 1067–1072.(18) Garcia-Rio, L.; Herves, P.; Leis, J. R.; Mejuto, J. C.; Perez-Juste,

J. J. Org. Chem. 1998, 11, 584–588.(19) Wells, D.; Drummond, C. J. Langmuir 1999, 15, 4713–4721.(20) Dreger, K.; Zou, B.; Mu, Z.; Galla, H. J.; Chi, L.; Fuchs, H.;

Schafer, H. J. Langmuir 2006, 22, 1619–1625.(21) Williams, R. J.; Phillips, J. N.; Mysels, K. J. Trans. Faraday Soc.

1955, 51, 728–737.(22) Zana, R. Langmuir 1996, 12, 1208–1211.(23) Ohta, A.; Toda, K.; Morimoto, Y.; Asakawa, T.; Miyagishi, S.

Colloids Surf., A 2007, 317, 316–322.(24) Srinivas, V.; Balasubramanian, D. Langmuir 1998, 14, 6658–6661.(25) Yoshida, N.; Matsuoka, K.; Moroi, Y. J. Colloid Interface Sci. 1997,

187, 388–395.

(26) Tsubone, K.; Rosen, M. J. J. Colloid Interface Sci. 2001, 244, 394–398.

(27) Mhaskar, S. Y.; Prasad, R. B. N.; Lakshminarayana, G. J. Am. OilChem. Soc. 1990, 67, 1015–1019.

(28) Gad, E. A. M.; El-Sukkary, M. M. A.; Ismail, D. A. J. Am. OilChem. Soc. 1997, 74, 43–47.

(29) Luan, Y.; Xu, J.; Yuan, S.; Xiao, L.; Zhang, Z. Colloids Surf., A2002, 210, 61–68.

(30) Mukerjee, P.; Mysels, K. J. Critical Micelle Concentration ofAqueous Surfactant Systems; National Bureau of Standards: Washington,DC, 1971.

(31) Reichardt, C. Chem. ReV. 1994, 94, 2319–2358.(32) Varadaraj, R.; Schaffer, H.; Bock, J.; Valint, P. Langmuir 1990, 6,

1372–1376.(33) Varadaraj, R.; Bock, J.; Valint, P.; Brons, N. Langmuir 1990, 6,

1376–1378.(34) Moran, C.; Clapes, P.; Comelles, F.; Garcia, T.; Perez, L.; Vinardell,

P.; Mitjans, M.; Infante, M. R. Langmuir 2001, 17, 5071–5075.(35) Perez, P.; Pinazo, A.; Vinardell, P.; Clapes, P.; Angelet, M.; Infante,

M. R. New J. Chem. 2002, 26, 1221–1227.

JP807396K

982 J. Phys. Chem. B, Vol. 113, No. 4, 2009 Faustino et al.