RSC Advances

REVIEW

Polydiacetylenes –

PDttUSaiuldsl

research, aiming to harness the unfor scientic and practical applica

aDepartment of Chemistry, Ben-Gurion Uni

Israel. E-mail: razj@bgu.ac.il; Fax: +972-8-6bIlse Katz Institute for Nanoscale Science and

Negev, Beer Sheva 84105, Israel

Cite this: RSC Adv., 2013, 3, 21192

Received 30th May 2013Accepted 29th August 2013

DOI: 10.1039/c3ra42639d

www.rsc.org/advances

21192 | RSC Adv., 2013, 3, 21192–21

recent molecular advances andapplications

Raz Jelinek*ab and Margarita Ritenberga

Polydiacetylenes (PDAs) comprise a class of chromatic polymers which have attracted significant interest

over the past 40 years as a promising platform for chemo- and bio-sensing. Specifically, the unique

colorimetric and fluorescent transformations of PDA, induced by varied external stimuli, are a core

property of these polymers, and have been widely exploited for diverse applications. In this review,

we focus on recent developments in PDA chemistry, materials, and practical applications. We summarize

the progress in development of new synthetic routes and assembly methods resulting in enhanced

chromatic properties and interesting molecular configurations. We further outline the challenges that

still exist for practical utilization of PDA technology, and possible future directions.

Introduction

Since the rst reports on polydiacetylene (PDA) synthesisappeared at the end of the 1960s from the laboratory ofWegner,1,2 these molecules have captured the imagination ofscientists and technologists alike due to their unique chromaticproperties. Specically, it has been shown that certain diac-etylene monomers can be aligned in solutions and polymerizedthrough ultraviolet (UV) irradiation, producing a conjugatedPDA network3,4 (Fig. 1). The unique feature of PDA systems hasbeen the observation that the conjugated PDA networks oenabsorb light in the visible spectral region, thereby exhibiting

rofessor Raz Jelinek is at theepartment of Chemistry andhe Ilse Katz Institute for Nano-echnology at Ben Gurionniversity of the Negev, Beerheva, Israel. His research aimst exploiting biomimetic chem-stry approaches for bothnderstanding important bio-ogical processes, as well aseveloping novel nano-tructures. He has been particu-arly active in polydiacetyleneique properties of the polymertions.

versity of the Negev, Beer Sheva 84105,

472943; Tel: +972-52-6839384

Technology, Ben-Gurion University of the

201

color, in most cases blue.5,6 Moreover, conjugated PDA canundergo phase changes, induced by varied environmentalstimuli, leading to dramatic colorimetric transformations thatare visible to the naked eye (Fig. 1). Another attractive feature ofPDA systems in the context of sensing applications has been theuorescence properties; blue phase PDA is non-uorescencewhile the red-phase conguration exhibits high uorescencewith minimal bleaching.7–9

Beside the intriguing chromatic properties of PDA, thediverse physical congurations of the PDA have attracted broadresearch interest. PDA systems have been shown to organize invesicles,10,11 Langmuir monolayers,12–14 self-assembled lms,15,16

and single crystals.17,18 PDA has been also assembled ascomponents within other “host” matrixes, including inorganicmatrixes,19–21 other polymers,22,23 and even living cells.24

Remarkably, it has been shown that PDA generally retains its

Margarita Ritenberg is a grad-uate student at the Departmentof Chemistry, Ben GurionUniversity of the Negev, BeerSheva, Israel. Her researchfocuses on biosensing applica-tions of polydiacetylenes andcoupling of polydiacetylene totransparent matrixes such assol–gel for nanotechnologyapplications.

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Fig. 1 Colorimetric properties of polydiacetylenes.

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chromatic properties in these congurations, thus opening theway to construction of varied sensing assemblies.

This review aims to summarize recent innovative develop-ments in PDA research. We do not cover here the broad PDAliterature since the inception of the eld, nor discussing thebasic structural and physical properties of PDA systems.

Several reviews on PDA properties and applications havebeen published in the past several years.25–27

Due to space limitations, we discuss below only selectedreports, designed to present the main aspects of the eld, withparticular emphasis on recent developments that open newscientic and technological horizons. Thematically, the Review isdivided into four parts: we begin with a brief overview on thebasic molecular properties of PDA. This is followed by sectionsdepicting synthetic routes for modication of the diacetylenemonomeric units, oen giving rise to polydiacetylene assembliesexhibiting distinct physico-chemical properties; new PDA-basedcomposite materials of PDA-based materials; and practical appli-cations emanating both from the development of new synthesisschemes as well as overall materials designs and properties.Overlap naturally exists between these topics, as many publica-tions span more than one of the above general topics.

Basic molecular properties of PDA

The unique chromatic properties of PDA systems arise from themolecular properties of the polymer. PDA is formed through 1,4addition of aligned diacetylenic monomers, initiated by ultra-violet (UV) irradiation (Fig. 1). The diacetylene monomers donot absorb light in the visible region, while polydiacetyleneappears intense blue (absorption peak at around 650 nm) due toelectron delocalization within the linear p-conjugated frame-work, and corresponding to a p–p* transition.

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As indicated above, the colorimetric transformations of PDA,induced by a variety of external stimuli, have likely been themost interesting and technologically-attractive feature of PDAsystems. The signicant shi of the absorption peak fromaround 640 nm (the blue phase) to around 500 nm (the redphase) is ascribed to disruption of the conjugated network,resulting in shorter electronic delocalization lengths. Thered phase of PDA is accompanied by intense uorescence,which further exhibits negligible bleaching, contributing toutilization of the uorescence properties in varied sensingapplications.

Despite decades of studies, elucidating the exact mecha-nisms responsible for the chromatic transformations of PDAhas not been fully accomplished. It has been recognized that theshis in spectral absorbance are closely linked to structuralmodications of the conjugated polymer framework.14 Earlymodels accounting for the spectral/structural modulationsproposed transformation of the polymer backbone from theene–yne to a butatriene conformation.28 Recent crystallographicand theoretical investigations have illuminated intimate struc-tural aspects pertaining to the chromatic properties. In partic-ular, it has been established that the pendant side-chains of PDAplay a prominent role in affecting the chromatic trans-formations. Specically, the interactions between the func-tional groups of the side-chains are believed to signicantlyaffect the overall conformation of the polymer chain, primarilyrotations around the C–C bonds (Fig. 1) affecting the planarityof the backbone and concomitant overlap between adjacent porbitals.14 Indeed, theoretical calculations suggested that evenrotation of a few degrees of the side-groups around the C–Cbond would give rise to a signicant change of the p-orbitaloverlap and resultant blue-red transition.29

The realization that PDA side-chains exhibit signicanteffects upon the chromatic properties of the polymer has led tointense research aiming to modulate PDA spectral responsethrough synthetic modications of side-chain functionalgroups. Efforts have been directed, for example, to alter thecrystal packing of the individual monomers – the essential pre-condition to photo-polymerization and the resultant linearpolymer chains – via side-chain modication. A notableconsequence of the close links between crystal packing andpendant side-chain orientation is the achievement of colorreversibility. While most of the early work on supramolecularPDA assemblies demonstrated irreversible color trans-formations, there have been an increasing number of reportsdepicting color-change reversibility via chemical modicationof the PDA side-chains, thus altering the molecular packing andtopochemical transformations within the polymer modules.30,31

Synthetic pathways

Early work in the eld has predominantly focused upon the“standard” diacetylene monomers 10,12-tricosadynoic acid and5,7-pentacosadiynoic acid (Fig. 2). These monomers, currentlycommercially available, can be aligned in aqueous solutionsand the hydrogen bond network maintained among thecarboxylic headgroups enable the occurrence of ene–yne

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Fig. 2 Diacetylene monomers.

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transformations and formation of the polymerized conjugatedbackbone system.32

Recent years have witnessed a proliferation of synthesisschemes producing novel diacetylene monomeric units.Numerous examples have been presented in the literature, andsome examples, by no means exhaustive, are presented in thefollowing. Interesting peptide–diacetylene monomers in whichthe diacetylene backbone is anked by peptide moietieshave been reported33 (Fig. 3). Some members of the peptide–diacetylene family could be polymerized using UV irradiation,although the chromatic properties were generally differentcompared to native PDA. Polymerization times, for example,were signicantly longer (around 30 minutes) and pH-depen-dent, and the colorimetric transformations in the PDA deriva-tives were not readily induced. The peptide–PDA assemblies,however, displayed both unique nano-structured congurations(nanowires, “nano-mesh” morphologies), as well as macro-scopic organization – producing potentially-useful hydrogelnetworks.

Other PDA–peptide conjugates have been synthesized,bestowing interesting properties to the resultant materials.Vesicles comprising a PDA–histidine derivative and PDA–pen-talysine which further contained a uorescent moiety, consti-tuted vehicles for binding and detection of lipopolysaccharides(LPS) – the prominent recognition units displayed on bacterialsurfaces.34 Specically, the organized positively-charged aminoresidues in the synthetically-modulated PDA vesicles mimicked

Fig. 3 Peptide–diacetylene monomers. Molecular structures of diacetylenesderivatized with diacids and short peptides, employed for construction ofsupramolecular assemblies.33 Reprinted with permission from S. R. Diegelmannet al., J. Am. Chem. Soc., 2012, 134, 2028–2031. Copyright (2012) AmericanChemical Society.

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the recognition surface of polymyxin-B, a natural antibioticwhich specically binds to LPS primarily through electrostaticattraction.35

While that work presents a nice example of diacetylenemonomer derivatization enabling distinct recognition capabil-ities, the modied vesicles in that case also exhibited photo-physical properties that were different from “conventional” PDAsystems. Specically, the PDA assembly displayed an interestinguorescence “turn-on” mechanism: the initial state of thevesicles, which were in the uorescent “red” phase, was non-uorescent due to energy transfer between the PDA network anda surface-displayed uorescent dye; binding of LPS-presentingbacteria to the vesicles prevented the energy transfer and gaverise to enhanced uorescence. A similar study depicted the useof peptide-displayed PDA for detection of trinitrotoluene (TNT),the common ingredient in explosives.36 The peptide moiety inthat system served as the recognition element for the TNTmolecules.

Monomeric diacetylene units have also been derivatized withnon-peptidic residues. An interesting scheme was recentlyreported in which “diacetylene macrocycle” units have beensynthesized, producing “columnar structures” upon polymeri-zation37 (Fig. 4). The thrust of that study has been the assemblyof porous “molecular columns” enabled through the polymer-ization process of the diacetylenic macrocycles. In essence, thepolymerized diacetylene network in this case provided the“scaffolding” for the columns, rather than the means foroptical/spectroscopic transformations.

A systematic study has recently investigated the crystallineorganizations of diacetylene monomers functionalized withdifferent phenyl-containing units.38 The goal of that work was toassess the polymerization pathways of the materials, particularlythe effect of the substituted moieties upon the packing of themonomeric diacetylenic units and feasibility of the concurrenttopochemical polymerization. Specically, the experimentsrevealed that despite the bulky phenyl-substituted headgroups,aromatic peruorophenyl–phenyl interactions facilitated effi-cient polymerization and formation of the conjugated PDAbackbone. This study highlights an important aspect of PDAchemistry, specically the effect of monomer modication uponpolymerization and photophysical properties. Indeed, whilediacetylene monomers can be readily manipulated via diversesynthetic routes, in many cases the resultant molecules do notundergo topotactic polymerization to the polymer phase since

Fig. 4 Columnar PDA. Diacetylene macrocycle monomeric unit (left), its self-assembly into columnar structures (middle), and polymerization (right). Reprintedwith permission from Y. Xu et al., J. Am. Chem. Soc., 2010, 132, 5334–5335.Copyright (2010) American Chemical Society.

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Fig. 5 Color reversibility in PDA–PVP composites. Chromatic reversibilityobserved when the PVP network was intercalated within the PDA framework(top). No reversibility occurred in a system in which larger PDA crystallites wereembedded in a PVP matrix (bottom). Reprinted with permission from Y. Gu et al.,Macromolecules, 2008, 41, 2299–2303. Copyright (2008) American ChemicalSociety.

Fig. 6 PDA-based microbubbles. Preparation of microbubbles comprising PDAsand surfactants via a microfluidic device. Reprinted with permission from Y. Parket al., Langmuir, 2012, 28, 3766–3772. Copyright (2012) American ChemicalSociety.

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the structural modications disrupt the monomer alignmentessential for the ene–yne transformation.39,40

Another recently-reported synthetic pathway has focusedupon modication of diacetylene monomers with a uorescentcoumarin headgroup.41 The display of the dyes gave rise tointeresting structural and optical properties upon polymeriza-tion. Somewhat unexpectedly, the relatively bulky coumarinmoieties did not prevent polymerization. Moreover, Langmuir–Blodgett lms of coumarin–PDA exhibited remarkable revers-ibility of temperature-induced color change. Also noteworthy,the polymerized lm assemblies were chiral even though thecoumarin–diacetylene monomers were achiral, conrmingthe distinct ordering of the functionalized diacetylene units inthe polymer conguration.

Attaining reversibility of PDA chromatic changes has beenamong the most remarkable achievements in this eld. In thatregard, synthetic progress has oen gone beyond establishing arm understanding of the molecular mechanisms pertaining tocolor reversibility in PDA systems. It is generally accepted thatreorganization of the hydrogen bond network through syntheticmanipulations of the diacetylene headgroups is the core factormaking possible reversible blue-red transformations of PDA.Accordingly, most reported reversible PDA systems haveemployed varied schemes for manipulating the polar head-groups of the polymer.

Almost all examples of reversible PDA-based systems havefocused upon thermally-induced transformations, i.e. blue-redchanges brought about by heating, while the reversible red-blue transformation occurring following cooling. Among thediacetylene units shown to affect color reversibility followingpolymerization were monomers displaying 2,2,2-triuoro-N-(4-hydroxyphenyl)acetamide,42 3-carboxypropylpentacosa-10,12-diynamide,43 azo chromophore-functionalized diacetylene,44

secondary amine salts,45 naphthylmethylammonium carbox-ylate,46 and non-polar benzyl moieties.47

Intriguing reversible thermochromism has been demon-strated in a supramolecular system in which PDA was notderivatized (i.e. the conventional 10,12-pentacosadiynoic acidhas been used).48 In that system, temperature-inducedreversible color transitions were traced to a hierarchicalorganization in which the PDA domains were encapsulatedwithin a poly(vinylpyrolidone) (PVP) matrix (Fig. 5). Theintercalation of PVP domains within the PDA framework wasthe likely factor enabling reorientation of the PDA headgroupsaffecting reversibility of the conjugated polymer networklength (and consequent reversible chromatic transitions).

Researchers have reported the use of synthetic derivatives ofdiacetylene monomers for assembly of other functional species.Fig. 6 depicts a microuidic scheme in which PDA micro-bubbles were prepared for potential use in biomedicalimaging.49 The diacetylene monomers in that assembly werefunctionalized with varied headgroups, particularly poly-ethylene-glycol (PEG), designed to achieve efficient embeddingof gas molecules (used as imaging contrast agents), and mini-mize bubble aggregation. Indeed, the PDA framework in thissystem was not aimed to achieve sensing capabilities throughthe colorimetric/uorescence properties of the polymer, but

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rather was employed as a resilient and stable gas-encapsulatingshell aimed at achieving a better stability of themicrobubbles inphysiological environments. Accordingly, these polymerizedshell microbubbles might function as contrast agents in ultra-sound imaging.50

PDA-based composite materials

Composite materials comprising PDA mixed with or coupled toother molecular species have been pursued, yielding in manycases advanced materials exhibiting interesting properties.PDA–carbon nanotubes (CNTs) are a case in point.51,52 In suchsystems, the surfaces of single-walled CNTs (SWCNTs) havebeen used as a “template” upon which organization and poly-merization of the diacetylene units occurred. The resultantcomposite materials exhibited intriguing properties.

In one study, “ring-shaped” polydiacetylene structuresformed upon the SWCNT surface were capable of solubilizing

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and stabilizing highly hydrophobic substances, such asmembrane proteins and dyes, through interactions with thependant side-chains of the polymer.51 Accordingly, such PDA–SWCNT constructs might nd uses as “smart detergents” incosmetics, membrane proteins structure determination, andothers.

While that work concentrated on the structural/functionalfeatures of PDA–SWCNT systems, it should be emphasizedthat SWCNTs are also expected to affect the photophysicalproperties of the nanotube-associated PDA. Signicantly, arecent study has demonstrated that CNTs not only provided aphysical framework upon which polymerization could becarried out, but also constituted a source of uorescentenergy, transferred to the PDA via Forster resonance energytransfer,53 giving rise to intense emission of the material in thenear infrared (NIR) spectral region.52 The PDA–CNT assem-blies could also take advantage of the known “stealth” prop-erties of CNTs, thus particularly employed in cellular imagingapplications.

A conceptually-similar PDA–nanostructure system hasutilized magnetic nanoparticles (NPs) as a template forassembly of the chromatic polymer.54 The organized PDA layersin this case were formed upon the surface of magnetic Fe2O3

NPs through non-covalent hydrogen bonds between the diac-etylene moieties and the polar surface of the MNPs. Remark-ably, the magnetic particles not only enabled the topotacticpolymerization of the monomers into the extended polymernetwork, but experiments demonstrated that the blue-redtransformation in this case could be induced by application of amagnetic eld (Fig. 7), presumably associated with localizedheating of the NP surface through alternating magnetic eld.This unusual “magnetochromic effect” might nd uses insensing and electro-optic applications.

Fig. 7 PDA–magnetic nanoparticle conjugates. Schematic illustration of thepreparation of “magnetochromic NPs” comprising Fe2O3 cores coated withdiacetylene moieties. Reprinted with permission from X. Chen et al., Angew.Chem., Int. Ed., 2011, 50, 5486–5489. Copyright (2011) John Wiley and Sons.

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Modulation of the diacetylene headgroups has led to prep-aration of self-assembled species displaying remarkable struc-tural and functional properties. A diacetylene monomercomposed of a long alkyl chain and bulky hydrophilic nitrilo-triacetate (NTA) headgroup (Fig. 8) was shown to undergounique self-assembly processes and, furthermore, exhibitpotentially useful biological imaging functionalities.55 Theresearchers have discovered that self-assembly of these diac-etylenic monomers can be modulated through the pH condi-tions of the solution. Indeed, remarkable morphologies couldbe attained through alteration of the solution acidity, includingribbons, twisted ribbons, spirals, micelles, and others. Thatwork underscored both the fundamental roles played by thediacetylene headgroups in shaping the self-assembly propertiesof the polymer, as well as the sophisticated synthetic meansavailable to modulate PDA structures and associatedfunctionalities.

Conjugation of PDA with inorganic, porous materials hasbeen a major route in PDA technology development. In general,porous materials constitute attractive targets for practicalapplications involving PDA. This is due to the large (internal)surface areas of porous matrixes useful for immobilization ofhigh polymer concentration, and transparency – makingpossible exploiting the optical/spectroscopic properties of PDAwithin the inorganic framework. An example of this concept hasbeen the incorporation of PDA within templates of anodizedaluminum oxide (AAO) – a popular porous matrix employed for“template-synthesis” applications.56 AAOs contain orderedporous “tubes” which dimensions can be tuned via control ofthe synthesis conditions. A recent study has demonstrated thatPDA “nano-bers” could be assembled within an AAOtemplate.20 That work underscored important facets of what canbe referred to as “template-directed PDA synthesis”.

Specically, the AAO template enabled fabrication of highlyuniform, crystalline PDA structures (Fig. 9). Furthermore, the

Fig. 8 Diacetylene–nitrilotriacetate (DA–NTA) monomers. Top: molecular struc-ture of the monomer; bottom: polymerization through UV irradiation – the bulkyheadgroup did not adversely affect the polymerization process. Reprinted withpermission from E. Gravel et al., Chem.–Eur. J., 2011, 18, 400–408. Copyright(2011) John Wiley and Sons.

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Fig. 9 PDA nanofibers synthesized in AAO templates. SEM (a–c) and TEM (d)images of PDA fibers embedded in an AAO template matrix. Reprinted from L.Tong et al., Fabrication, structural characterization and sensing properties ofpolydiacetylene nanofibers templated from anodized aluminum oxide, Sens.Actuators, B, 155, 584–591, Copyright (2011), with permission from Elsevier.

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crystalline PDA bers could be released from the AAO hostmatrix without adversely affecting their structural integrity.Particularly noteworthy is the fact that PDA could retain itschromatic properties – polymerization and chromatic changesinduced by external stimuli.

In some experimental setups, PDA has not been used as asignal-generating component but rather as “smart scaffolding”.A pertinent example has been the assembly of “nano-containers” for controlled drug release comprising PDA and acyclodextrin (CD) derivative.57 The vesicular particles in that

Fig. 10 Intercalation of alkylamines within crystalline PDA. Schematic illustrationof the guest alkylamine molecules intercalated within the PDA network. Thecrystal sheets are inclined by 43� following alkylamine intercalation. Reprintedwith permission from T. Shimogaki and A. Matsumoto,Macromolecules, 2011, 44,3323–3327. Copyright (2011) American Chemical Society.

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system could be triggered to release their molecular cargothrough two externally-applied stimuli. Specically, light illu-mination (e.g. photo-activation) was accomplished throughcoupling of the CD moieties to photo-switchable azobenzene.58

Furthermore, pH-induced release could be achieved via theknown sensitivity of the PDA network to pH changes. Alto-gether, such PDA-based nano-containers point to potentialapplications of PDA systems in drug delivery, taking advantageof their high stability, on the one hand, and intrinsic structuraltriggering mechanisms, on the other hand.

Several studies have examined the structural and chromaticconsequences of association of guest species with PDA hostmatrixes. Unlike most PDA investigations focusing upon vesic-ular PDA assemblies or thin lms, a recent report described theeffect of alkylamine guest molecules upon the organization andproperties of PDA crystals.59 Fig. 10 depicts the impact of analkylamine molecular guest upon the organization of the PDAhost. Specically, the researchers have found that intercalationamong the alkyl chains of the guest molecules affected both thecrystal structure of the resultant supramolecular assembly, aswell as extent and dynamics of the chromatic transitions of thePDA crystallites following addition of the alkylamines.

Applications of PDA systems

Historically and up to the present, the main drawing point ofPDA systems have been their remarkable chromatic sensingcapabilities. In particular, the incorporation of diverse molec-ular recognition elements within PDA assemblies has madePDA a highly versatile sensing platform. Importantly, since thePDA headgroups are intrinsically negatively-charged,60 manyreported biosensing applications have focused on detection ofpositively-charged amphiphilic molecules.61 Inclusion of posi-tive units within PDA assemblies, however, can bestow sensingcapabilities of negative molecules as well. A recent example hasbeen the use of liposomes comprising diacetylenic units cova-lently displaying positive NH3

+ moieties for colorimetric detec-tion of heparin, an important polyanionic biological molecule.62

Interestingly, that study indicates that chromatic trans-formations did not occur in all cases in which positive unitswere displayed on the liposome surface; rather, color transi-tions were recorded only when the positive residues wereattached to distinct molecular “arms”. Furthermore, the mostpronounced chromatic response was induced when sizeableanionic polymers (i.e. heparin) were present in the testedsolution, highlighting sensitivity of PDA systems to intimatevariations even in electrostatic interactions between the analyteand vesicle surface.

The signicance of steric factors in affecting the chromatictransformations of PDA vesicles induced by molecular recog-nition events was further analysed.63 That study utilized amicro-array liposome-based system to investigate the uores-cence changes induced by interactions between peptidecomponents of the inuenza virus (as well as the viral particlesthemselves) and their respective antibodies. Based upon theexperimental data, the researchers have concluded that stericrepulsion between vesicle-bound ligands play more signicant

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Fig. 12 “Turn-on” fluorescence detection of apoptotic cells based upon phos-phatidylserine (PS) recognition. Principle of “turn-on” fluorescence detection ofapoptotic cells through binding of Zn(PDA) to PS displayed upon the cell exterior.Reprinted with permission from Y. S. Cho et al., Chem.–Asian J., 2013, 8, 755–759.Copyright (2013) John Wiley and Sons.

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roles in affecting the structural/chromatic transformations ofPDA as compared to the binding strength between the analyteand vesicle-displayed recognition element (Fig. 11). This inter-pretation, if proven to be universal for PDA systems, is impor-tant, since it could shape the design of PDA-based sensorsaiming to achieve optimal sensitivity.

As mentioned above, the incorporation of recognitionelements within PDA-based vesicles has been the most widely-used vehicle for sensing applications using the conjugatedpolymer, and diverse systems have been reported. A recentstudy has demonstrated detection of apoptotic cells using PDAvesicles.64 That sensing scheme was based upon the well-recognized phenomenon in which increased exposure ofphosphatidylserine (PS) occurs on the surface of apoptoticcells.65 Accordingly, the researchers succeeded to achievespecic response to apoptotic cells through covalent attach-ment of a Zn2+-stabilized complex onto the PDA network(Fig. 12). The binding between the complex and PS units in thatsystem was the recognition event triggering the colorimetrictransformations of the vesicles. An interesting construct hasbeen reported in which PDA vesicles comprising antibodiesagainst the H5N1 strain of inuenza virus were embedded uponthe surface of polystyrene beads.66 The antibody was covalentlyattached to the bead–PDA system, enabling detection of viralparticles. The bead–PDA constructs were stable in differentsolution conditions, enabled naked-eye detection of viralparticles, and might be implemented in microuidic deviceapplications through placing the beads within devicemicrochannels.

Another example of the versatility and sensing power ofPDA assemblies derivatized with recognition units is a recentreport describing colorimetric detection of gaseous

Fig. 11 Significance of steric repulsion vs. analyte binding for PDA chromatictransitions. Effects of different stimuli upon the mechanical perturbation andconcomitant color transformations of PDA vesicles. Reprinted with permissionfrom S. Seo et al., Macromol. Rapid Commun., 2013, 34, 743–748 Copyright(2013) John Wiley and Sons.

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compounds by PDA-based vesicles comprising oxime func-tional groups.67 The signicance of this work lies in theremarkable specicity attained by the oxime–PDA vesiclestowards toxic volatile species that might be employed inchemical warfare scenarios.

An interesting vapor sensing application accomplishedthrough a PDA-based approach has been recently reported.68 Inthat study, the researchers combined several notable featuresgenerating a potentially powerful sensing platform. First, theysucceeded to couple diacetylene monomers to a lter paper,without adversely affecting the polymerization (and chromatic)properties of the PDA framework. Second, the coupled PDA–paper system exhibited sensitivity to vapors of volatile organiccompounds (VOCs), undergoing visible colorimetric trans-formations in the presence of the compounds in the gas phase.Moreover, to achieve specicity, the researchers prepared amatrix in which each component comprised a diacetylenemonomer displaying a different headgroup. Together, the arrayof distinctly-functionalized PDA units produced colorimetric“ngerprints” for different VOCs, akin to “articial nose”detection concepts.69

In few cases, displayed functional units can bestow chro-matic response to diagnostically-important anionic species. Anexample of such a system has been the construction of thinlms comprising PDA derivatized with imidazolium units, andthe use of such lms for sensing anionic surfactants.70 Inter-estingly, the imidazolium-functionalized PDA exhibitedunusual blue-yellow and blue-orange transformations (besidesthe more conventional blue-red changes), as well as reversibilityof thermochromic transitions.

In some instances, the sensitivity of PDA detection schemeshas been enhanced through more complex, hybrid detectionschemes in which the PDA detector was coupled to orthogonalsignal enhancement mechanisms. An example of such anapproach has been a system for detection of the cancer markerprostate-specic antigen (PSA) through PDA chromaticresponse.71 The basic sensing approach relied on conjugatinganti-PSA monoclonal antibodies (mAbs) onto the PDA vesiclesurface. However, to amplify the chromatic signal magneticbeads coupled to polyclonal antibodies (pAbs) against PSA werefurther added to the reaction mixture. The consequent bindingof the pAb–beads to the vesicles produced a signicant

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Fig. 14 Dip-coated PDA/sol–gel film. SEM image showing the protruding PDAdomains within the sol–gel matrix.

Fig. 15 Cationic PDA micelles for gene delivery. Photopolymerization of thediacetylene–surfactant (A), and its micelle organization (B). Adapted from E.Morin et al., Bioconjugate Chem., 2011, 22, 1916–1923. Copyright (2011)American Chemical Society.

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mechanical perturbation giving rise to enhanced chromaticresponse of the PDA.

Coupling PDA with other functional materials could openavenues to intriguing novel applications. A recent studydemonstrated that a solution of surfactants and diacetylenemonomers could be used as ink.72 Application of the diac-etylene-containing ink onto paper through conventional inkjetprinting produced chromatic patterns (Fig. 13). Remarkably,upon selection of the appropriate diacetylene monomers, thethermochromic transitions of the PDA-based ink were revers-ible – e.g. from blue to red upon heating, back to blue followingcooling.

Increasing the sensitivity of PDA chromatic properties toenvironmental stimuli through coupling to additionalspecies has been a major driving force for research effortsaiming to create PDA-based sensing devices. Fig. 14 depicts arecent example of a PDA/sol–gel composite material fordetection of bacterial biolms.73 In that study, PDA/sol–gellms were assembled on glass substrates through a dip-coating technique.74 Microscopic analysis of the resultantlms indicated that distinct PDA domains were formedwithin the glassy sol–gel matrix (Fig. 14). Remarkably, whenthe PDA/sol–gel lms were placed in solutions containingbiolm-forming bacteria, they underwent gradual blue-redtransformations.

The colorimetric transitions (and corresponding uorescentemission) were ascribed in that case to the dense biolm matrixforming upon the PDA domains, consequently producing thelocalized mechanical stress inducing the structural modulationof PDA.

The conjugated network of PDA provides a useful meansfor fabricating rigid, stable supramolecular assemblies. Asynthetic route has been recently presented in which diac-etylenic amphiphile monomers were designed, subsequentlyforming micellar structures that could be used for genedelivery applications.75 Fig. 15 depicts the experimental

Fig. 13 PDA-based inkjet printing. Photographs of a regular printer paperprinted with a diacetylene–surfactant mixture. The diacetylene ink retains thechromatic properties – polymerized to the conjugated blue phase and under-going the blue-red transition following heating. Reprinted with permission fromB. Yoon et al., Adv. Mater., 2011, 23, 5492–5497. Copyright (2011) JohnWiley andSons.

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scheme. The diacetylene surfactant monomers in this casedisplayed positive moieties, designed to anchor DNA moieties– thus forming lipoplex-type assemblies.76 The polymerizedPDA–surfactant micelles were stable in physiological solu-tions, and, importantly, exhibited lower cytotoxicitycompared to conventional surfactant-based lipoplexes.Notably, the cationic PDA micelles were shown to be effectivegene delivery vehicles, and photopolymerization actuallyenhanced their gene transfection efficiency. This result islikely related to the high stability of the conjugated polymerframework, facilitating better transport of the gene cargo tothe cell nucleus compared to more conventional non cross-linked lipoplexes.

Summary and future directions

Since their rst appearance on Science stage more than 40 yearsago, polydiacetylenes have evolved and branched into diverseelds and applications, both in basic research as well as tech-nology. Recent years have witnessed a signicant expansion inPDA research, from the “classical” applications of PDA in bio-sensing and chemosensing, towards new schemes demon-strating PDA-based materials as drug delivery platforms,

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RSC Advances Review

molecular carriers, and others. This review summarized themain aspects of current PDA research and recent developmentsin synthesis, materials design, and practical applications of thisunique polymer.

Importantly, while tremendous progress and sophisticationof PDA systems have been achieved in recent years, identifyingdenite mechanistic aspects pertaining to PDA chromaticproperties and transitions is still somewhat “work-in-progress”.In particular, elucidation of the precise linkage between thecolorimetric/uorescence transitions and structural changes ofPDA networks is still sought. In this context, the comprehensivesynthetic “tool-box” currently available to researchers in theeld should enable further testing of varied hypotheses per-taining to the relationships between changes of PDA crystalpacking induced by external stimuli and corresponding struc-tural/chromatic transformations. Such physico-chemical anal-yses are expected to constitute an active research area in thePDA eld.

In conclusion, like many scientic disciplines before it, the“critical mass” of research groups and activities focused on PDApromise to greatly expand the impact and future promise of theeld. New synthetic pathways will continue to modulatesupramolecular PDA assemblies, and particularly the photo-physical properties of the materials. While the unique colori-metric and uorescent characteristics of PDA will likelycontinue to attract signicant interest, it is expected that othermolecular features of the polymer, such as enhanced stability indifferent solutions, morphological control, and macroscopicproperties, will be increasingly exploited. Last but not least,aer a long “gestation”, practical utilization of PDA systems isexpected to appear in greater abundance in the technology andcommercial arenas.

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