Compartmentalization and Unidirectional Cross-Domain Molecule

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Letter Cite This: ACS Macro Lett. 2018, 7, 572−575

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Compartmentalization and Unidirectional Cross-Domain Molecule Shuttling of Organometallic Single-Chain Nanoparticles Zhigang Cui, Leilei Huang, Yi Ding, Xuechao Zhu, Xinhua Lu, and Yuanli Cai* State-Local Joint Engineering Laboratory of Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China S Supporting Information *

ABSTRACT: Compartmentalization and unidirectional crossdomain molecule shuttling are omnipresent in proteins, and play key roles in molecular recognition, enzymatic reaction, and other living functions. Nanomachinery design emulating these biological functions is being considered as one of the most ambitious and challenging tasks in modern chemistry and nanoscience. Here, we present a biomimetic nanomachinery design using single-chain technology. Stepwise complex of the outer blocks of water-soluble linear ABC triblock terpolymer to copper ions yields dumbbell-shaped single-chain nanoparticle. A novel nanomachine capable of compartmentalization and unidirectional cross-domain molecule shuttling has been achieved upon ascorbic acid reduction, leading to synergistically donating/accepting copper centers between discrete double heads, overall dumbbell-to-tadpole configurational transition, and intake of oxidized ascorbic acid into reconstructed head. Subsequent air oxidation results in the inverse molecule shuttling and configurational transition processes. This is the first demonstration of biomimetic nanomachinery design that is capable of compartmentalization and unidirectional cross-domain molecule shuttling, exemplified simply using a new single-chain technology.

C

SCNP-1 (Figure 1A) was prepared by stepwise complex of the

ompartmentalization and unidirectional cross-domain molecule shuttling are omnipresent in proteins, and are essential for molecular recognition, enzymatic reaction, and other functions. For example, molluscan hemocyanin contains a set of subunits that are arranged like a pearl chain.1 Synergistic redox of the copper centers enables cross-domain dioxygen molecule transport. Nanomachinery design emulating these biological behaviors is being considered as one of the most ambitious and challenging tasks in modern chemistry and nanoscience. Rowan and co-workers explored optically healable,2 shape-memory,3 supramolecular polymers. Singlechain technology4,5 represents another direction of biomimicry. Meijer, 6 Barner-Kowollik, 7 Zimmerman, 8 Sawamoto, 9 Berda,10−12 and others13−16 developed single-chain nanoparticle (SCNP) catalysts. While single-chain compartmentalization17−22 has been attained, biomimetic nanomachinery design associated with unidirectional cross-domain molecule shuttling is an important yet elusive research goal. Herein, we present a nanomachinery design associated with the compartmentalization and unidirectional cross-domain molecule shuttling in ultrafine SCNP system. To this end, we prepared water-soluble linear ABC triblock terpolymer [A: poly(histamine acrylamide hydrochloride), PHisAM; B: poly(2hydroxypropyl methacrylamide), PHPMA; C: poly(2-aminoethyl methacrylamide hydrochloride), PAEMA] at a chain length of A58B57C58 and a dispersity (Đ) of 1.12 via visible light mediated RAFT polymerization22−25 and end-group protection (Supporting Information, SI, Figure S1). The dumbbell-shaped © XXXX American Chemical Society

outer blocks to copper ions (Figure S2) via neutralization from

Figure 1. (A) Schematic illustration, (B) diameter profile, and (C) TEM image of dumbbell-shaped SCNP-1. Received: March 16, 2018 Accepted: April 18, 2018

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DOI: 10.1021/acsmacrolett.8b00199 ACS Macro Lett. 2018, 7, 572−575

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ACS Macro Letters pH 2.5 to 6.4 at [Cu(II)]0/[ligands]0 = 1/4, taking advantages of the difference of imidazole and NH2 motifs in the basicity and coordination.22 Dynamic light scattering (DLS, Figure 1B) shows the shrinkage to 6.4 nm in diameter (Dh,DLS), similar to NMR diffusion-ordered spectroscopy DOSYassessed Dh,DOSY of 6.1 nm (Figure S3). Sample was freeze-dried and visualized by transmission electron microscopy (TEM). Figure 1C clearly displays discrete double heads at number-weighed diameters (Dn) of 13.6 and 9.4 nm (Figure S4). This SCNP served as a nanomachine prototype of cross-domain molecule shuttling. First, SCNP-1 cupric centers were reduced using ascorbic acid (AA). Reaction proceeded at varied feed ratios, defined to be f = [AA]0/[Cu(II)]0, in argon-saturated solution at pH 6.4, 25 °C, overnight. UV−vis spectroscopy (Figure 2A) indicates

Figure 3. (A) Diameter profile and (B) TEM image of SCNP-2. (C) Suggested molecule shuttling mechanism.

SCNPs of PHPMA60-b-PHisAM56, PHPMA55-b-PAEMA57 at f = 4.0 also brought about ∼50% ligands dissociation and intake of Ox-AA into reassembled heads (Figures S8 and S9). As a result, a nanomachine capable of the unidirectional molecule shuttling was obtained by synergistically donating/accepting copper centers between discrete double heads and hence a dumbbell-to-tadpole configuration transition depicted in Figure 3C. To put inverse unidirectional molecule shuttling into effect, we oxidized the cuprous centers of SCNP-2 via bubbling fresh air at 8−10 bubbles/min at 25 °C. Fresh air was obtained by removal of CO2 and water vapor via passing through an anhydrous KOH column. During air oxidation, sample was taken and saturated with argon gas. Figure 4A shows that the cuprous centers survived in early 0.5 h and oxidation

Figure 2. (A) UV−vis and (B) 1H NMR spectra of SCNP-1 and those upon the redox reaction depicted in (C).

full reduction at f = 1.5. FTIR spectroscopy unveils that the reduction led to the NH2-ligand dissociation and formation of exclusive Cu(I)-imidazole complex at f = 2.0 (Figure S5), suggesting the unfolding of C-block. The reaction was inspected using 1H NMR spectroscopy. Figure 2B shows that signals of the outer blocks in SCNP-1 disappeared, as compared to those of polymer precursor. Cblock’s signal c reappeared thoroughly at f ≥ 1.5 (Figure S6) due to metal reduction (Figure 2A). In contrast, A-block’s signals m, n, and o disappeared at f = 1.0−2.0. These results confirmed C-head disassembly and A-head reassembly, as observed by FTIR spectroscopy (Figure S5). Unexpectedly, signals r′, t′ of Ox-AA disappeared at f = 2.0 due to the in situ intake into reassembled A-head. Figure 3A shows that redox at f = 2.0 induced size increase to Dh,DLS = 7.7 nm, comparable to Dh,DOSY = 7.5 nm (Figure S3). Figures 3B displays the spherical shape of dried sample at a Dn = 15.6 nm (Figure S7). Thus, SCNP-1 has been transformed to tadpole-shape SCNP,20,26 namely, SCNP-2. It is not surprising because the copper reduction induced the decrease of coordination number. In principle, A-block imidazole coordinated more preferentially than C-block NH2,27 which inevitably led to the NH2-to-imidazole dynamic ligand exchange. As such, the unidirectional copper shuttling out of C-head into A-head was achieved. The control experiment by reducing Cu(II)-

Figure 4. (A) UV−vis and (B) 1H NMR spectra of SCNP-2 and those upon air-oxidation reactions depicted in (C). 573

DOI: 10.1021/acsmacrolett.8b00199 ACS Macro Lett. 2018, 7, 572−575

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ACS Macro Letters

f = 8.0 yielded micelles, similar to those formed upon the addition of NaCl (6-fold molar to copper) into SCNP-2 solution (Figure S11). In summary, we introduced a new nanomachinery design that involved compartmentalization and unidirectional crossdomain molecule shuttling using single-chain technology. It was validated using the dumbbell-shaped SCNP prepared by stepwise complex of the outer blocks of ABC-type linear triblock terpolymer to copper ions. The sequential AA reduction and air oxidation resulted in the unidirectional molecule shuttling between discrete double heads, leading to dumbbell-to-tadpole-to-dumbbell configurational transition and the intake of Ox-AA into as-reassembled heads. AA protected cuprous centers but large excess led to the undesired salting-out effect. We envision that the alteration of ligand motifs or metal centers will lead to unprecedented machinery behaviors. This is the first demonstration of a nanomachinery design that is capable of compartmentalization and unidirectional crossdomain molecule shuttling, analogous to the living functions of proteins, exemplified using a new single-chain technology.

commenced in 1 h. In contrast, the residual AA was oxidized in 0.5 h and thoroughly in 1 h based on decreased signals s, t (Figure 4B). Thus, the residual AA acted as an antioxidant to protect the cuprous centers. Figure 4B displays that C-block signal c survived in the early 0.5 h, decreased in 1 h, disappeared in 8 h, synchronously with the cuprous oxidation duration (Figure 4A). In contrast, the signals of A-block are undetectable throughout the oxidation. C-block coordinated once again, leading to simultaneously refolding of C-segments and decrease of solution ζ-potential (Figure 5A). Strikingly, Ox-AA signals r′, s′, t′ increased in 1 h,

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsmacrolett.8b00199. Synthesis, reactions, characterizations, and additional date (PDF).

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Yuanli Cai: 0000-0001-5473-485X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by National Natural Science Foundation of China (21474069, 21774083), Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Figure 5. (A) Unfolded C-block (PAEMA%) and ζ-potential variation. (B) Diameter profile and (C) TEM image of SCNP-3. (D) Suggested molecule shuttling mechanism.

REFERENCES

(1) Markl, J. Evolution of Molluscan Hemocyanin Structures. Biochim. Biophys. Acta, Proteins Proteomics 2013, 1834, 1840−1852. (2) Burnworth, M.; Tang, L.; Kumpfer, J. R.; Duncan, A. J.; Beyer, F. L.; Fiore, G. L.; Rowan, S. J.; Weder, C. Optically Healable Supramolecular Polymers. Nature 2011, 472, 334−337. (3) Kumpfer, J. R.; Rowan, S. J. Thermo-, Photo-, and ChemoResponsive Shape-Memory Properties from Photo-Cross-Linked Metallo-Supramolecular Polymers. J. Am. Chem. Soc. 2011, 133, 12866−12874. (4) Ouchi, M.; Badi, N.; Lutz, J.-F.; Sawamoto, M. Single-Chain Technology using Discrete Synthetic Macromolecules. Nat. Chem. 2011, 3, 917−924. (5) Hanlon, A. M.; Lyon, C. K.; Berda, E. B. What Is Next in SingleChain Nanoparticles? Macromolecules 2016, 49, 2−14. (6) Terashima, T.; Mes, T.; De Greef, T. F. A.; Gillissen, M. A. J.; Besenius, P.; Palmans, A. R. A.; Meijer, E. W. Single-Chain Folding of Polymers for Catalytic Systems in Water. J. Am. Chem. Soc. 2011, 133, 4742−4745.

decreased in 4 h, and disappeared in 8 h, synchronously with the C-block refolding duration. The results unveiled that Cblock refolded with the in situ intake of Ox-AA into reconstructed C-head. Figure 5B shows the chain compaction to Dh,DLS = 6.8 nm, Dh,DOSY = 6.7 nm (Figure S3). Figure 5C clearly displays the discrete double heads of reassembled SCNPs at Dn = 15.5 and 12.6 nm (Figure S10), namely, SCNP-3. Therefore, the subsequent aerial oxidation brought about the inverse molecule shuttling and configurational transition depicted in Figure 5D. Notably, AA was ionized at pH 6.4 (pKa = 4.04).28 The salt effect should be considered for intramolecular reassembly. As such, it is necessary to control the feed ratio within f = 1.5− 2.5. Otherwise, large excess of AA will induce undesired intermolecular self-assembly.29,30 For instance, the reduction at 574

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ACS Macro Letters (7) Knoefel, N. D.; Rothfuss, H.; Willenbacher, J.; Barner-Kowollik, C.; Roesky, P. W. Platinum(II)-Crosslinked Single-Chain Nanoparticles: An Approach towards Recyclable Homogeneous Catalysts. Angew. Chem., Int. Ed. 2017, 56, 4950−4954. (8) Bai, Y.; Feng, X.; Xing, H.; Xu, Y.; Kim, B. K.; Baig, N.; Zhou, T.; Gewirth, A. A.; Lu, Y.; Oldfield, E.; Zimmerman, S. C. A Highly Efficient Single-Chain Metal Organic Nanoparticle Catalyst for Alkyne-Azide ″Click″ Reactions in Water and in Cells. J. Am. Chem. Soc. 2016, 138, 11077−11080. (9) Azuma, Y.; Terashima, T.; Sawamoto, M. Self-Folding Polymer Iron Catalysts for Living Radical Polymerization. ACS Macro Lett. 2017, 6, 830−835. (10) Tooley, C. A.; Pazicni, S.; Berda, E. B. Toward a Tunable Synthetic FeFe Hydrogenase Mimic: Single-Chain Nanoparticles Functionalized with a Single Diiron Cluster. Polym. Chem. 2015, 6, 7646−7651. (11) Rodriguez, K. J.; Hanlon, A. M.; Lyon, C. K.; Cole, J. P.; Tuten, B. T.; Tooley, C. A.; Berda, E. B.; Pazicni, S. Porphyrin-Cored Polymer Nanoparticles: Macromolecular Models for Heme Iron Coordination. Inorg. Chem. 2016, 55, 9493−9496. (12) Cole, J. P.; Hanlon, A. M.; Rodriguez, K. J.; Berda, E. B. ProteinLike Structure and Activity in Synthetic Polymers. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 191−206. (13) Mavila, S.; Rozenberg, I.; Lemcoff, N. G. A General Approach to Mono- and Bimetallic Organometallic Nanoparticles. Chem. Sci. 2014, 5, 4196−4203. (14) Sanchez-Sanchez, A.; Arbe, A.; Colmenero, J.; Pomposo, J. A. Metallo-Folded Single-Chain Nanoparticles with Catalytic Selectivity. ACS Macro Lett. 2014, 3, 439−443. (15) Thanneeru, S.; Duay, S. S.; Jin, L.; Fu, Y.; Angeles-Bon, A. M.; He, J. Single Chain Polymeric Nanoparticles to Promote Selective Hydroxylation Reactions of Phenol Catalyzed by Copper. ACS Macro Lett. 2017, 6, 652−656. (16) Zhang, Y.; Tan, R.; Gao, M.; Hao, P.; Yin, D. Bio-Inspired Single-Chain Polymeric Nanoparticles Containing a Chiral Salen TiIV Complex for Highly Enantioselective Sulfoxidation in Water. Green Chem. 2017, 19, 1182−1193. (17) Hosono, N.; Gillissen, M. A. J.; Li, Y. C.; Sheiko, S. S.; Palmans, A. R. A.; Meijer, E. W. Orthogonal Self-Assembly in Folding Block Copolymers. J. Am. Chem. Soc. 2013, 135, 501−510. (18) Roy, R. K.; Lutz, J. F. Compartmentalization of Single Polymer Chains by Stepwise Intramolecular Cross-Linking of SequenceControlled Macromolecules. J. Am. Chem. Soc. 2014, 136, 12888− 12891. (19) Claus, T. K.; Zhang, J.; Martin, L.; Hartlieb, M.; Mutlu, H.; Perrier, S.; Delaittre, G.; Barner-Kowollik, C. Stepwise Light-Induced Dual Compaction of Single-Chain Nanoparticles. Macromol. Rapid Commun. 2017, 38, 1700264. (20) Matsumoto, M.; Terashima, T.; Matsumoto, K.; Takenaka, M.; Sawamoto, M. Compartmentalization Technologies via Self-Assembly and Cross Linking of Amphiphilic Random Block Copolymers in Water. J. Am. Chem. Soc. 2017, 139, 7164−7167. (21) Cao, H.; Cui, Z.; Gao, P.; Ding, Y.; Zhu, X.; Lu, X.; Cai, Y. Metal-Folded Single-Chain Nanoparticle: Nanoclusters and SelfAssembled Reduction-Responsive Sub-5-nm Discrete Subdomains. Macromol. Rapid Commun. 2017, 38, 1700269. (22) Cui, Z.; Cao, H.; Ding, Y.; Gao, P.; Lu, X.; Cai, Y. Compartmentalization of an ABC Triblock Copolymer Single-Chain Nanoparticle via Coordination-Driven Orthogonal Self-Assembly. Polym. Chem. 2017, 8, 3755−3763. (23) Lu, L.; Zhang, H.; Yang, N.; Cai, Y. Toward Rapid and WellControlled Ambient Temperature RAFT Polymerization under UVVis Radiation: Effect of Radiation Wave Range. Macromolecules 2006, 39, 3770−3776. (24) Shi, Y.; Liu, G.; Gao, H.; Lu, L.; Cai, Y. Effect of Mild Visible Light on Rapid Aqueous RAFT Polymerization of Water-Soluble Acrylic Monomers at Ambient Temperature: Initiation and Activation. Macromolecules 2009, 42, 3917−3926.

(25) Tong, J.; Shi, Y.; Liu, G.; Huang, T.; Xu, N.; Zhu, Z.; Cai, Y. Visible Light Mediated Fast Iterative RAFT Synthesis of Amino-Based Reactive Copolymers in Water at 20 °C. Macromol. Rapid Commun. 2013, 34, 1827−1832. (26) Mavila, S.; Diesendruck, C. E.; Linde, S.; Amir, L.; Shikler, R.; Lemcoff, N. G. Polycyclooctadiene Complexes of Rhodium(I): Direct Access to Organometallic Nanoparticles. Angew. Chem., Int. Ed. 2013, 52, 5767−5770. (27) Banerjea, D.; Kaden, T. A.; Sigel, H. Enhanced Stability of Ternary Complexes in Solution through the Participation of Heteroaromatic N Bases. Comparison of the Coordination Tendency of Pyridine, Imidazole, Ammonia, Acetate, and Hydrogen Phosphate toward Metal Ion Nitrilotriacetate Complexes. Inorg. Chem. 1981, 20, 2586−2590. (28) Gramlich, G.; Zhang, J. Y.; Nau, W. M. Increased Antioxidant Reactivity of Vitamin C at Low pH in Model Membranes. J. Am. Chem. Soc. 2002, 124, 11252−11253. (29) Wen, J.; Yuan, L.; Yang, Y.; Liu, L.; Zhao, H. Self-Assembly of Monotethered Single-Chain Nanoparticle Shape Amphiphiles. ACS Macro Lett. 2013, 2, 100−106. (30) Fan, W.; Liu, L.; Zhao, H. Co-assembly of Patchy Polymeric Micelles and Protein Molecules. Angew. Chem., Int. Ed. 2017, 56, 8844−8848.

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