molecules Review Radical Polymerization of Alkyl 2-Cyanoacrylates Review RadicalCormac Duffy Polymerization 1,2, Per B. Zetterlund 3 and of Fawaz Alkyl Aldabbagh 2-Cyanoacrylates 2,4,* 1. Henkel Ireland Operations & Research Limited, Whitestown, Dublin 24, Ireland; [email protected] Cormac2. School Duffy of 1,2Chemistry,, Per B. ZetterlundNational University3 and Fawaz of Ireland Aldabbagh Galway, University2,4,* ID Road, Galway H91 TK33, Ireland 3. Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, The University of 1 Henkel Ireland Operations & Research Limited, Whitestown, Dublin 24, Ireland; [email protected] New South Wales, Sydney, NSW 2052, Australia; [email protected] 2 School of Chemistry, National University of Ireland Galway, University Road, Galway H91 TK33, Ireland 4. Present address: Department of Pharmacy, School of Life Sciences, Pharmacy & Chemistry, Kingston 3 Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, University, Penrhyn Road, Kingston upon Thames KT1 2EE, UK The University of New South Wales, Sydney, NSW 2052, Australia; [email protected] * Correspondence: [email protected]; Tel.: +44-20-8417-2528 4 Present address: Department of Pharmacy, School of Life Sciences, Pharmacy & Chemistry, Received:Kingston University,3 February Penrhyn2018; Accepted: Road, Kingston 17 February upon 2018 Thames; Published: KT1 2EE, 20 February UK 2018 * Correspondence: [email protected]; Tel.: +44-20-8417-2528 Abstract: Cyanoacrylates (CAs) are well-known fast-setting adhesives, which are sold as liquids in Received: 3 February 2018; Accepted: 17 February 2018; Published: 20 February 2018 the presence of stabilizers. Rapid anionic polymerization on exposure to surface moisture is Abstract:responsibleCyanoacrylates for instant (CAs) adhesion. are well-known The more fast-setting difficult adhesives,, but synthetically which are sold more as liquidsuseful in r theadical presencepolymerization of stabilizers. is only Rapid possible anionic under polymerization acidic conditions on exposure. Recommendations to surface moisture on the ishandling responsible of CAs forand instant the resulting adhesion. polymers The more are difficult, provided but herein. synthetically In this review more article useful, radicalafter a general polymerization description is of onlymonomer possible underand polymer acidic conditions. properties Recommendations, radical homo- and on co thepolymerization handling of CAs studies and the are resulting described, polymersalong with are providedan overview herein. of nanoparticle In this review preparations article, after. A asumm generalary descriptionof our recent ofly monomer reported andradical polymerpolymerization properties, of radical CAs, homo- using and reversible copolymerization addition- studiesfragmentation are described, chain alongtransfer with (RAFT) an overviewpolymerization of nanoparticle, is provided preparations.. A summary of our recently reported radical polymerization of CAs, using reversible addition-fragmentation chain transfer (RAFT) polymerization, is provided. Keywords: cyanoacrylate; instant adhesives; super glue; polymerization; radical Keywords: cyanoacrylate; instant adhesives; super glue; polymerization; radical 1. Introduction 1. Introduction Alkyl 2-cyanoacrylates or cyanoacrylates (CAs) are a family of vinyl monomers renowned for theirAlkyl high 2-cyanoacrylates reactivity, instant or cyanoacrylatesadhesive properties (CAs), an ared awide family-ranging of vinyl applications monomers [1 renowned–6]. Short forchain theirCA highs, like reactivity, methyl instant- and ethyl adhesive 2-cyanoacrylate properties, and have wide-ranging found great applications utility as the [1– 6major]. Short components chain CAs, of likeindustrial methyl- and and ethyl household 2-cyanoacrylate instant haveadhesives found or great “super utility glues”, as the including major components those manufactured of industrial at andHenkel household under instant the Loctite adhesives brand or (Table “super 1) glues”, [4–6]. including those manufactured at Henkel under the Loctite brand (Table1)[4–6]. Table 1. Structure and commercial uses of common cyanoacrylates (CAs). Table 1. Structure and commercial uses of common cyanoacrylates (CAs). Structure R Uses Structure RMe Loctite Uses 496 super bonder MeEt LoctiteLoctite 496 401 super instant bonder adhesive i-PropylEt Loctite 401Root instant canal adhesive sealant i-Propyl Root canal sealant nn-Butyl-Butyl Skin/surgicalSkin/surgical adhesive adhesive 2-Octyl2-Octyl SkinSkin surgical surgical adhesive adhesive Allyl High temperature adhesive Allyl High temperature adhesive β-Methoxyethyl Low odor adhesive ββ--EthoxyethylMethoxyethyl LowLow odor odo adhesiver adhesive βPhenylethyl-Ethoxyethyl AdhesiveLow odo tapesr adhesive Phenylethyl Adhesive tapes Longer-chain CAs, such as n-butyl and 2-octyl 2-cyanoacrylate (Figure1), have found utility as surgical suture replacements for skin and tissue adhesives [7–10]. Poly(CAs) have gained recognition for numerous biomedical applications due to their favorable biocompatibility, biodegradability, and low toxicity. Colloidal nanoparticles derived from CAs have shown great promise in the field of drug and vaccineMolecules delivery 2018, 23 [, 11465–;16 doi:].10.3390/molecules23020465 CA is used in latent fingerprint development in forensicwww.mdpi.com/journal/ science, wherebymolecules Molecules 2018, 23, 465; doi:10.3390/molecules23020465 www.mdpi.com/journal/molecules Molecules 2018, 23, 465 2 of 22 Longer-chain CAs, such as n-butyl and 2-octyl 2-cyanoacrylate (Figure 1), have found utility as surgical suture replacements for skin and tissue adhesives [7–10]. Poly(CAs) have gained recognition for numerous biomedical applications due to their favorable biocompatibility, Moleculesbiodegradability2018, 23, 465, and low toxicity. Colloidal nanoparticles derived from CAs have shown 2great of 21 promise in the field of drug and vaccine delivery [11–16]. CA is used in latent fingerprint development in forensic science, whereby CA vapors adheres to trace amino acids present in the CAfingerprint vapors adheres [17,18]. to Due trace to amino its unsaturated acids present ester in the group fingerprint, allyl [217-cyanoacrylate,18]. Due to its has unsaturated the ability ester to group,undergo allyl crosslinking 2-cyanoacrylate reactions has theat elevated ability to temper undergoatures, crosslinking a feature reactions that has at found elevated use temperatures, in thermally aresistant feature thatadhe hassive founds [5] use. β- inMethoxyethyl thermally resistant- and β adhesives-ethoxyethyl [5]. β2-Methoxyethyl--cyanoacrylate andhaveβ -ethoxyethyllower vapor 2-cyanoacrylatepressures compared have to lower shorter vapor chain pressures CAs and compared are often to used shorter as low chain odo CAsr adhesives. and are oftenAdditionally, used as lowthese odor adhesives adhesives. avoid Additionally, a phenomenon these adhesivescharacteristic avoid of atheir phenomenon shorter chain characteristic counterparts of their, known shorter as chain“blooming”, counterparts, whereby known polymerized as “blooming”, monomer whereby vapor polymerizedis deposited monomeras a fine chalky vapor ispowder deposited on the as asurface fine chalky near powderan adhesive on the bond surface-line, nearand anare adhesivesometimes bond-line, referred andto as are “low sometimes-bloom” referredadhesives to [4] as. “low-bloom”Phenylethyl adhesives2-cyanoacrylate [4]. Phenylethyl differs from 2-cyanoacrylate the previously differs named from CA thes in previously that it is nameda solid CAsand inis thatutilized it is ain solid industrial and is adhesive utilized intapes industrial and films adhesive [19]. tapes and films [19]. (a) (b) (c) Figure 1. (a) 2-octyl (b) β-ethoxyethyl (c) phenylethyl 2-cyanoacrylates. Figure 1. (a) 2-octyl (b) β-ethoxyethyl (c) phenylethyl 2-cyanoacrylates. The general monomer chemistry, synthesis, modes of polymerization, and the physical The general monomer chemistry, synthesis, modes of polymerization, and the physical characteristics of the resulting polymers, along with several toxicological evaluations, have been characteristics of the resulting polymers, along with several toxicological evaluations, have been detailed in a number of reviews [1–15,20–22]. In this review, after a general overview of reactivity and detailed in a number of reviews [1–15,20–22]. In this review, after a general overview of reactivity properties, the focus is the radical polymerization of CAs, with the advantages over the more facile and properties, the focus is the radical polymerization of CAs, with the advantages over the more anionic pathway clearly outlined. facile anionic pathway clearly outlined. 2. General Reactivity and Properties 2. General Reactivity and Properties 2.1. Anionic-Type Polymerizations 2.1. Anionic-type Polymerizations The high reactivity of CAs is attributed to the strong electron-withdrawing nitrile (CN) and ester The high reactivity of CAs is attributed to the strong electron-withdrawing nitrile (CN) and (CO2R) groups attached to the α-carbon of the double bond. The β-carbon of CAs is activated towards nucleophiles,ester (CO2R) groups such as attached anions, as to wellthe α as-carbon weak bases,of the water,double and bond. alcohols The β (Scheme-carbon 1of). CA In ans is adhesive activated context,towards polymerizationnucleophiles, such or curingas anions, occurs as well through as weak rapid