Biocompatible zinc(II) 8-(dihydroimidazolyl)quinoline complex and its catalytic application for synthesis of poly(L,L-lactide) Dmitrii S. Bolotin a,⇑ , Viktor Korzhikov-Vlakh a,⇑ , Ekaterina Sinitsyna a , Sevilya N. Yunusova a , Vitalii V. Suslonov b , Anton Shetnev c , Angelina Osipyan a , Mikhail Krasavin a , Vadim Yu. Kukushkin a,⇑ a Institute of Chemistry, Saint Petersburg State University, Universitetskaya Nab., 7/9, Saint Petersburg, Russian Federation b Center for X-ray Diffraction Studies, Saint Petersburg State University, Universitetskii Pr., 26, Saint Petersburg, Russian Federation c The Ushinsky Yaroslavl State Pedagogical University, Respublikanskaya St., 108, Yaroslavl 150000, Russian Federation article info Article history: Received 9 January 2019 Revised 27 February 2019 Accepted 4 March 2019 Keywords: Quinoline Metal complexes Homogeneous catalysis Lactide Ring-opening polymerization abstract A 1:1 reaction of 8-(dihydroimidazolyl)quinoline (abbreviated as L) with MCl 2 Á2H 2 O (M = Co II , Ni II , Cu II , Zn II ) conducted in EtOAc (for Zn II and Cu II ) or MeOH (Ni II and Co II ) at 50 °C for 10 min provided the respec- tive air- and shelf-stable [MCl 2 L] complexes (94–96%). The catalytic activity of these well-defined species was evaluated in L-lactide ring-opening polymerization (ROP) that was conducted in the presence of 2-hydroxyethylmethacrylate (HEMA) as a nucleophilic initiator. The biocompatible zinc(II) complex was found to be more catalytically active in ROP compared to the other three complexes as well as SnOct 2 , a common reference catalyst. The zinc(II)-catalyzed ROP also gives the macromolecular product with the lowest polydispersity index (1.2). The applicability of the HEMA-terminated PLA, prepared in the presence of the [ZnCl 2 L] complex, was demonstrated when PLA was converted into amphiphilic copoly- mer PLA-PEG via the thiol-ene click reaction. The PLA-PEG copolymer was shown to form nanospheres (calculated mean diameter 95 ± 10 nm) characterized by low particle size distribution. This – along with anticipated lower toxicity of [ZnCl 2 L] traces in the polymer – makes these nanospheres potentially applicable as vehicles for intravenous drug delivery. Ó 2019 Elsevier Inc. All rights reserved. 1. Introduction Biodegradable and biocompatible polyesters, such as poly (L,L-lactide) (PLA), have found many important applications in biomedical research [1] – e. g., graft manufacturing for regenera- tive medicine [2], scaffolds for tissue engineering [3], and con- trolled drug delivery systems [4]. PLA is generally synthesized via ring-opening polymerization (ROP) of the 2,6-dimethyl-1,4-diox ane-2,5-dione, commonly referred to as ‘‘dilactide” or simply ‘‘lactide” [5]. Although tin(II) octoate (SnOct 2 ) [6] and aluminum (III) alkoxides [7] were successfully used in many studies for bulk polymerization of L,L-lactide, the search for new catalysts for fast polymerization in solution is still ongoing [8]. The use of various new complexes in the polymerization of lac- tide as well as lactones was reported in numerous publications, which have been critically analyzed in several reviews [9]. Although it appears that SnOct 2 is still the most frequently used catalyst in the ROP of lactides and lactones [10], new catalysts are being developed for this reaction that are based on biocompat- ible metals, provide better control over the polymerization process, and work at lower temperatures. Alkali and alkaline earth metals complexes were shown to be very active in ROP of lactide but could not provide sufficient control over the polymerization process [11]. More promising results were obtained for lanthanide complexes [12], which allow fast ROP in solution and substantial control over the polymerization process. However, such complexes, similarly to Sn(Oct) 2 , are not biocompatible. A wealth of studies that have appeared in the literature involved lactide ROP in the presence of a metal-free organocatalyst [9c,13]. Despite obvious advantages associated with organocatalysis, such as non-contamination of the polymer product with trace metals (which has special significance is the latter is intended for biomedical applications), applying an organocatalystic system requires substantial catalyst load [14] and rather long polymerization times [15]. Controlled polymeriza- tion often requires using inert atmosphere [16]. Moreover, intro- duction of terminal groups via co-initiation by an alcohol molecule is not very straightforward in case of organocatalysis. Another disadvantage of organocatalysts is their potential toxicity. In light of this, employing zinc(II)-based catalysts with quinoline https://doi.org/10.1016/j.jcat.2019.03.002 0021-9517/Ó 2019 Elsevier Inc. All rights reserved. ⇑ Corresponding authors. E-mail addresses: d.s.bolotin@spbu.ru (D.S. Bolotin), v.korzhikov-vlakh@spbu.ru (V. Korzhikov-Vlakh), v.kukushkin@spbu.ru (V.Yu. Kukushkin). Journal of Catalysis 372 (2019) 362–369 Contents lists available at ScienceDirect Journal of Catalysis journal homepage: www.elsevier.com/locate/jcat