Iterative Convergent Synthesis of Large Cyclic Polymers and Block Copolymers with Discrete Molecular Weights

Article abstract of DOI:10.1021/jacs.0c04202

We report here the synthesis of cyclic polymers and block copolymers consisting of discrete numbers of repeating units without linear contaminants. The synthesis utilizes the intramolecular cyclization of end-functionalized poly(rac-lactide) (PLA) and its block copolymers with as many as 512 lactic acid units (37 kDa), synthesized by the iterative linear convergence of orthogonally protected building blocks. By exploiting the change in hydrodynamic volume upon cyclization of the linear polymers, macrocyclic polymers were isolated without linear precursors by preparative size-exclusion chromatography as a purification method. Our procedure also allowed the synthesis of a monodisperse cyclic block copolymer in a desired block ratio as a single compound (14 kDa).

Full text of DOI:10.1021/jacs.0c04202

Subscriber access provided by FLORIDA INTL UNIV
Communication
Iterative Convergent Synthesis of Large Cyclic Polymers
and Block Copolymers with Discrete Molecular Weights
Mo Beom Koo, Seul Woo Lee, Jung Min Lee, and Kyoung Taek Kim
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 23 Jul 2020
Downloaded from pubs.acs.org on July 23, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 6
Journal of the American Chemical Society
Iterative Convergent Synthesis of Large Cyclic Polymers and
Block Copolymers with Discrete Molecular Weights
1
2
3
4
5
6
Mo Beom Koo,1,† Seul Woo Lee,1,† Jung Min Lee,1 and Kyoung Taek Kim1,*
1Department of Chemistry, Seoul National University, Seoul 08826, Korea
7
8
9
ABSTRACT: We report here the synthesis of cyclic polymers and block copolymers consisting of discrete numbers of repeating
units without linear contaminants. The synthesis utilizes the intramolecular cyclization of end-functionalized poly(rac-lactide) (PLA)
and its block copolymers with as many as 512 lactic acid units (37 kDa), synthesized by the iterative linear convergence of
orthogonally protected building blocks. Exploiting the change in hydrodynamic volume upon cyclization of the linear polymers,
macrocyclic polymers were isolated without linear precursors by preparative size-exclusion chromatography as a purification method.
Our procedure also allowed the synthesis of a monodisperse cyclic block copolymer in a desired block ratio as a single compound
(14 kDa).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Cyclic polymers have attracted scientific and practical interest
because of their unique chemical and physical properties arising
from the topological constraints of their chain conformations
and the absence of chain ends.1-5 Cyclic polymers have been
synthesized by ring expansion via homologation or
polymerization6-10 and the intramolecular cyclization of end-
functionalized linear polymers.11–14 However, because of ring-
opening or incomplete ring closure, these methods could
generate linear polymers as contaminants that significantly
confound the unique physical behaviors of the cyclic
polymers.15,16 Despite ingenious efforts to prepare highly pure
cyclic polymers,17–20 the presence of linear contaminants could
not be ruled out, in particular, for high molecular-weight cyclic
polymers with molecular weight distributions.
intramolecular cyclization due to the topological constraints on
its conformation.29 Therefore, the reaction mixture containing
cyclic and linear polymers having the same molecular weight
should be separable by SEC because of the linear contaminant’s
larger hydrodynamic volume in solution.
Synthetic polymers composed of a large discrete number of
repeating units, referred to herein as discrete polymers, can be
transformed to topological polymers without statistical
uncertainty with regard to chemical structures. These polymers
could serve as precision materials that might reveal the
chemical and physical properties obscured by statistical
distribution of molecular weights. One of the challenges in the
preparation of discrete polymer rings is the scalability of the
molecular weight of discrete linear polymer precursors. The
iterative convergent approach to discrete polymers has attracted
recent interest as an alternative to solid-phase synthesis.21,22
A
number of monodisperse macromolecules have been
successfully synthesized by the iterative linear convergence of
orthogonally protected repeating units.23–27 However, the
molecular weight, one of the defining characteristics of
polymers, in these examples has been limited to the domain of
oligomers (Figure 1A). We recently reported the cross-
convergent synthesis of sequence-defined polyesters composed
of two distinct -hydroxy acids.28 Utilizing the molecular
weight difference between reagents and coupled products, we
adopted size-exclusion chromatography (SEC) as a purification
method for the discrete polymers. Preparative SEC (prep-SEC)
could be performed for the preparation of high molecular-
weight monodisperse polymers (up to 512 repeating units) on
gram-scale.
Figure 1. (A) Monodisperse oligomers and polymers
synthesized by the iterative linear convergence of repeating
units. (B) Intramolecular cyclization of discrete PLA (dPLA)
and its block copolymer to form cyclic polymers and a cyclic
block copolymer without linear impurities.
The iterative convergent pathway was utilized to synthesize
monodisperse polylactides composed of large discrete numbers
of repeating units (dPLAs) with rac-lactide having benzyl ester
and t-butyldimethylsilyl (TBDMS) ether protecting groups
(LA2) as the repeating unit (Figure 2A).25,26 One linear
convergence process constitutes the deprotections and a
coupling step: A portion of LA2 is converted to HO-LA2-Bz
by selective deprotection of the silyl protecting group with
BF3∙Et2O at room temperature. The other portion is subjected to
Here we show that discrete polymers and block copolymers
synthesized by the iterative convergent method could be
valuable precursors for the preparation of high molecular-
weight cyclic polymers and block copolymers without linear
contaminants via intramolecular cyclization (Figure 1B). The
hydrodynamic volume of
a
polymer decreases upon
ACS Paragon Plus Environment

Journal of the American Chemical Society
hydrogenation with triethylsilane and Pd/C, which yields
Page 2 of 6
TBDMS-LAn-COOH gradually decreases from 92% for LA64
to 62% for LA512 (Figure S12–S15 and Table S6). To
investigate the limit of the linear convergence by esterification
between the chain ends of high molecular-weight precursors,
we synthesized the dPLA composed of 1024 lactic acid units
(76 kDa). Using an equimolar mixture of precursors, the
coupling to LA1024 only proceeds in low yield (< 5%). Then,
we used excess HO-LA512-Bz (2 eq.) relative to TBDMS-
LA512-COOH for esterification over 24 h. By integrating the
peak areas corresponding to LA1024 and its precursors, GPC
analysis revealed a coupling yield of 59% with respect to
TBDMS-LA512-COOH (Figure S16). GPC and MALDI-TOF
analyses confirmed the successful synthesis of the high
molecular-weight dPLA (Figure 2B and Figure S5, S11), which
is, to the best of our knowledge, the largest linear polymer
isolated as a single compound.
TBDMS-LA2-COOH quantitatively.30 Stoichiometric amounts
of these coupling partners are converged with EDC and 4-
(dimethylamino)pyridinium p-toluenesulfonate (DPTS) to
afford LA4 in high yield (> 90%). Iterations of the linear
convergence exponentially increase the number of repeating
units of dPLA, up to 1024 lactic acid units. Compared to the
stepwise addition of individual monomers on a solid support,
the convergent pathway requires a minimal number of coupling
steps to achieve high molecular-weight discrete polymers.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
dPLAs synthesized by the linear convergent method possess
orthogonally protected functional groups at their chain ends,
which can be elaborated to desired functionalities. The hydroxy
and carboxylic acid termini of LAn were sequentially
deprotected and converted to acetylene and azide groups,
respectively, which afforded Alk-LAn-N3 for an intramolecular
click reaction catalyzed by CuBr (Figure 1B). To prevent
intermolecular click reactions, we adopted the pseudo-dilution
conditions reported by Grayson and coworkers.8 A THF
solution of Alk-LAn-N3 was introduced to a solution of CuBr/
N,N,N′,N″,N‴-pentamethyldiethylenetriamine (PMDETA) by
syringe pump (For detailed procedures, see the Supporting
Information). Investigation of the reaction mixture after
Figure 2. (A) Iterative convergent synthesis of dPLA up to
1024 repeating units. The red dotted square indicates a
convergence of linear precursors. The number inside a circling
arrow refers to the number of iterations of the convergence. (B)
Combined MALDI-TOF mass spectra of dPLAs.
addition by GPC revealed the emergence of
a peak
corresponding to half the original molecular weight of the linear
precursors and the disappearance of the precursor peak (Figure
3C and Figure S17). The integration of deconvoluted peaks in
the GPC traces indicates that the yield of the intramolecular
cyclization of dPLA gradually decreases from 99% for c-LA32
to 73% for c-LA256, as the end-to-end distance of dPLA
increases with molecular weight (Figure S18–S22 and Table
S7). In particular, c-LA512 (37063.42 Da) can be formed only
in low yield (30%, Figure S22), indicating the exponentially
diminishing probability of the end-to-end cycloaddition of the
high molecular weight Alk-LA512-N3.34
As the molecular weight of LAn increased, the separation of
dPLA from coupling precursors by flash column
chromatography became increasingly difficult due to the
diminishing affinity differences between the dPLA and
precursors toward the stationary phase.31–33 Therefore, LA64
and larger dPLAs were purified by prep-SEC with a loading of
up to 1 g of the reaction mixture per separation (See the
Supporting Information for details). Because the molecular-
weight difference between the HO- and COOH-precursors and
the coupled dPLA persists throughout the iterative linear
convergence sequence (Figure S5), prep-SEC guarantees the
separation of dPLA up to the separation limit of SEC (~ 1
MDa). To ensure the complete removal of unreacted precursors
having half the molecular weight of the coupled LAn, prep-
SEC was carried out in a recycling condition (Figure S1 and
S2). This method greatly simplifies the purification of high
molecular-weight dPLAs, facilitating efficient synthesis in
multi-gram quantities.28 After 7 iterations of the linear
convergence and SEC purification from LA4, LA512 was
synthesized on gram scale. The dPLAs were characterized
The difference in the hydrodynamic radii of the linear and
cyclic dPLAs having the same molecular weight was exploited
(Figure 3D and Figure S17) for purification of macrocycles by
prep-SEC35. By this technique, the cyclic dPLAs, c-LAn (n =
32, 64, 128, 256, and 512) were obtained as pure macrocycles
without linear impurities. For c-LA512, extra prep-SEC runs
were required for separation (Figure S31). 1H NMR spectra of
the purified c-LAn show the complete consumption of end
groups (Figure 3A and B). GPC and MALDI-TOF mass
analyses confirmed the absence of unreacted linear impurities
and high molecular-weight dPLAs stemming from
intermolecular click reaction (Figure 3C–E, and S25–S29).
The dPLAs and their macrocycles with a wide range of
molecular weights provide the opportunity to study the effect of
the topology on their physical properties of a polymer without
confounding by the presence of linear contaminants. A Flory-
Fox plot of the glass transition temperatures (Tg) of LA32–
LA512 against the 1/M values (Figure S32) shows that the Tg of
the LAn decreases linearly as a function of 1/M. The Tg of an
infinitely long LAn (Tg,∞ = 327.1 K) is in agreement with the
literature values obtained with conventional amorphous
1
unambiguously by H and 13C NMR, GPC, and MALDI-TOF
mass spectrometry (Figure 2 and Figure S3–S11).
The iterative synthesis of dPLAs relies on linear convergence
of the macromolecular precursors, which becomes increasingly
difficult in proportion to the increase of the molecular weight of
the coupling precursors. When estimated by the deconvolution
of the GPC traces of the reaction mixture, the yield for the
coupling reaction of an equimolar mixture of HO-LAn-Bz and
ACS Paragon Plus Environment

Page 3 of 6
Journal of the American Chemical Society
PLAs.36 The topological constraints and absence of end groups
of the c-LAn result in contracted conformations and reduced
free volumes, which translates to the increase of Tg compared
to linear dPLAs of the same molecular weight. Due to the
absence of chain ends, the Tg values of cyclic dPLAs show a
marked difference in the Flory-Fox plot.13
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 3. (A) 1H NMR spectra of cyclic dPLA c-LA32 and its linear precursor. (B) 1H NMR spectra of cyclic dPLAs showing the absence
of linear contaminants. The NMR spectrum of c-LA512 was omitted because its peaks were indistinguishable from the background noise.
(C) GPC results for LA512 and c-LA512 indicating the reduction in hydrodynamic volume upon ring closure. (D) Plot of the apparent
molecular weight (g/mol) of linear (filled circles) and cyclic (open circles) dPLAs measured at the SEC peak maximum against the number
of repeating units. (E) Combined MALDI-TOF mass spectra of cyclic dPLAs.
The convergent synthesis of dPLAs can be extended to the
formation of block copolymers without molecular weight
distribution by choosing heterogeneous coupling precursors for
the final convergence, hereafter referred to as a hetero-
convergence. As a demonstration, we chose monodisperse
poly(rac-phenyllactic acid) consisting of 64 repeating units
(PL64) as partner for hetero-convergence with LA64, which
yielded the diblock copolymer without molecular weight
distribution. The resulting discrete diblock copolymer, LA64-
b-PL64 was free from contaminants, and fully characterized by
NMR, GPC, and MALDI-TOF mass spectrometry (Figure 4
and Figure S36). The discrete block copolymer was further
elaborated to form cyclic block copolymer c-LA64-b-PL64 by
the intramolecular click reaction between its chain ends.
Analogous to the discrete dPLAs and their cyclic polymers, c-
LA64-b-PL64 demonstrates a reduced hydrodynamic volume
for the cyclic block copolymer compared to those of the linear
precursors at the same molecular weight (Figure 4B and C). The
resulting cyclic block copolymer without linear impurities was
copolymer were self-assembled in solution. Dioxane solutions
of LA64-b-PL64 and c-LA64-b-PL64 were directly introduced
to methanol, and the resulting suspensions were dialyzed
against pure water for 24 h. Dynamic light scattering (DLS) of
the suspensions indicates that both the linear and cyclic discrete
block copolymers self-assembled into nanoaggregates having
average diameters of 783 nm (polydispersity (PD) = 0.145) for
LA64-b-PL64 and 117 nm (PD = 0.083) for c-LA64-b-PL64
(Figure S39.). Transmission electron microscopy (TEM) and
cryogenic-TEM (cryo-TEM) images showed that the self-
assembled structures of these block copolymers were spherical
aggregates. The EM images of these aggregates support the
particle size results obtained by DLS (Figure S38), which
suggested that the topological differences among the block
copolymers could have a significant influence on their self-
assembly behavior.38
In summary, we demonstrated the synthesis of cyclic
polymers and block copolymers having discrete molecular
weights. Exploiting the reduction in hydrodynamic volume
upon cyclization of these monodisperse polymers, we isolated
pure discrete cyclic PLAs composed of large numbers of
repeating units without linear impurities by preparative SEC in
a scalable manner in quantities and molecular weight. The
procedure reported here could be employed for the synthesis of
1
purified by prep-SEC, and fully characterized by H NMR,
GPC, and MALDI-TOF mass (Figure 4 and Figure S34 and
S37).
To investigate the effect of their topology on the self-
assembly of block copolymers,37 a linear and cyclic block
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 6
discrete linear and cyclic block copolymers with predetermined
ACKNOWLEDGMENT
1
2
3
4
5
6
7
8
block ratios. Our method should allow the access to discrete
polymers and block copolymers of a desired topology for a wide
range of molecular weights. These polymers without structural
uncertainty could serve as model systems for the exploration of
the physical and chemical properties of synthetic
macromolecules without statistical distribution in chemical
structures, which could lead to a new understanding of polymer
properties and applications.
This work was supported by National Research Foundation (NRF)
of Korea (NRF-2019R1A2C3007541). We also thank Seoul
National University (SNU) for the support by Creative-Pioneering
Researchers Program (305-20190050).
REFERENCES
(1) Kricheldorf. H. R. Cyclic Polymers: Synthetic Strategies and
Physical Properties. J. Polym. Sci. Part A: Polym. Chem. 2010, 48,
251–284.
(2) Tezuka, Y; Oike, H. Topological polymer chemistry. Prog.
Polym. Sci. 2002, 27, 1069-1122.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3) Habuchi, S.; Satoh, N.; Yamamoto, T.; Tezuka, Y. Single-
molecule study on polymer diffusion in a melt state: Effect of chain
topology. Angew. Chem. Int. Ed. 2010, 122, 1460-1463.
(4) Yamamoto, T; Tezuka, Y. Cyclic polymers revealing topology
effects upon self-assemblies, dynamics and responses. Soft Matter,
2015, 11, 7458-7468.
(5) Divandari, M.; Trachsel, L.; Yan, W.; Rosenboom,J-G.; Spencer,
N. D.; Zenobi-Wong, M.; Morgese, G.; Ramakrishna, S. N.; Benetti, E.
M. Surface Density Variation within Cyclic Polymer Brushes Reveals
Topology Effects on Their Nanotribological and Biopassive Properties.
ACS Macro Lett. 2018, 7, 1455−1460.
(6) Shea, K. J.; Lee. S. Y.; Busch, B. B. A New Strategy for the
Synthesis of Macrocycles. The Polyhomologation of Boracylanes. J.
Org. Chem. 1998, 63, 5746–5747.
(7) Culkin, D. A.; Jeong, W.; Csihony, S.; Gomez, E. D.; Balsara,
N. P.; Hedrick, J. L.; Waymouth, R. M. Zwitterionic Polymerization of
Lactide to Cyclic Poly(lactide) by using N-Heterocyclic Carbene
Organocatalysts. Angew. Chem. Int. Ed. 2007, 46, 2627–2630.
(8) Bielawski, C. W.; Benite, D.; Grubbs, R. H. An “Endless” Route
to Cyclic Polymers. Science 2002. 297, 2014–2044.
(9) Guo, L.; Zhang, D. Cyclic Poly(α-peptoid)s and Their Block
Copolymers from N-Heterocyclic Carbene-Mediated Ring-Opening
Polymerization of N-Substituted N-Carboxyanhydrides. J. Am. Chem.
Soc. 2009, 131, 18072–18074.
(10) Gonsales, S. A.; Kubo, T.; Flint, M. K.; Abboud, K. A.;
Summerlin, B. S.; Veige, A. S. Highly Tactic Cyclic Polynorbornens:
Stereoselective Ring Expansion Metathesis Polymerization of
Norbornene Catalyzed by a New Tethered Tungsten-Alkylidene
Catalyst. J. Am. Chem. Soc. 2016, 138, 4996–4999.
(11) Laurent, B. A.; Grayson, S. M. Synthetic Approaches for the
Preparation of Cyclic Polymers. Chem. Soc. Rev. 2009, 38, 2202–2213.
(12) Laurent, B. A.; Grayson, S. M. An Efficient Route to Well-
Defined Macrocyclic Polymers via “Click” Cyclization. J. Am. Chem.
Soc. 2006, 128, 4238–4239.
(13) Ge, Z.; Zhou, Y.; Xu, J.; Liu, H.; Chen. D.; Liu, S. High-
Efficiency Preparation of Macrocyclic Diblock Copolymers via
Selective Click Reaction in Micellar Media. J. Am. Chem. Soc. 2009,
131, 1628–1629.
(14) Xu, J.; Ye, J.; Liu, S. Synthesis of Well-Defined Cyclic Poly(N-
isopropylacrylamide) via Click Chemistry and Its Unique Thermal
Phase Transition Behavior. Macromolecules 2007, 40, 9103–9110.
(15) Kapnistos, M.; Lang, M.; Vlassopoulos, D.; Pyckhout-Hintzen,
W.; Richter, D.; Cho, D.; Chang, T.; Rubinstein, M. Unexpected
Power-Law Stress Relaxation of Entangled Ring Polymers. Nat. Mater.
2008, 7, 997–1002.
(16) Gao, L.; Oh, J.; Tu, Y.; Chang, T.; Li, C. Y. Glass Transition
Temperature of Cyclic Polystyrene and the Linear Counterpart
Contamination Effect. Polymer 2019, 170, 198–203.
(17) He, Q.; Mao, J.; Wesdemiotis, C.; Quirk, R. P.; Foster, M. D.
Synthesis and Isomeric Characterization of Well-Defined 8-Shaped
Polystyrene Using Anionic Polymerization, Silicon Chloride Linking
Chemistry, and Metathesis Ring Closure. Macromolecules 2017, 50,
5779-5789.
(18) Haque, F. M.; Grayson, S. M. The synthesis, properties and
potential applications of cyclic polymers. Nat. Chem. 2020, 12, 433-
444.
Figure 4. (A) Synthesis of cyclic block copolymers. a: Et3SiH,
Pd/C; 2-azidoethanol, EDC, DPTS. b: BF3•Et2O; 4-pentynoic acid,
EDC, DPTS. c: CuBr, PMDETA. (B) GPC traces of dPLA and dPL
precursors and their linear diblock and cyclic block copolymers.
(C) MALDI-TOF mass spectra of constituent polymer blocks and
linear and cyclic block copolymers.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website.
Synthesis and full characterization for dPLAs, cyclic dPLAs, and
linear- and cyclic-block copolymers. GPC analysis of the coupling
and cyclization. Self-assembly of linear and cyclic block
copolymers (PDF).
AUTHOR INFORMATION
Corresponding Author
Kyoung Taek Kim – Department of Chemistry, Seoul National
University, 1 Gwanak Road, Seoul 08826, Korea; Email:
ktkim72@snu.ac.kr
Author Contributions
†M. B. Koo and S. W. Lee contributed equally.
Notes
The authors declare no competing financial interest.
ACS Paragon Plus Environment

Page 5 of 6
Journal of the American Chemical Society
(19) Elupula, R.; Oh, J.; Haque, F. M.; Chang, T.; Grayson, S. M.
(30) Mandal, P. K.; McMurray, J. S. Pd–C-Indued Catalytic Transfer
Hydrogenation with triethylsilane. J. Org. Chem. 2007, 72, 6599–6601.
(31) Lawrence, J.; Lee, S.-H.; Abdilla, A.; Nothling, M. D.; Ren, J.
M.; Knight, A. S.; Fleischmann, C.; Li, Y.; Abrams, A. S.; Schmidt, B.
V. K. J.; Hawker, M. C.; Connal, L. A.; McGrath, A. J.; Clark, P. G.;
Gutekunst, W. R.; Hawker, C. J. A Versatile and Scalable Strategy to
Discrete Oligomers. J. Am. Chem. Soc. 2016, 138, 6306–6310.
(32) De Neve, J.; Have, J. J.; Harrisson, S.; Junkers, T.
Deconstructing Oligomer Distributions: Discrete Species and Artificial
Distributions. Angew. Chem. Int. Ed. 2019, 58, 13869–13873.
(33) Haven, J. J.; Junkers, T. Quasi-monodisperse Polymer Libraries
via Flash Column Chromatography: Correlating Dispersity with Glass
Transition. Polym. Chem. 2019, 10, 679–682.
Determining the Origins of Impurities during Azide-Alkyne Click
Cyclization of Polystyrene. Macromolecules 2016, 49, 4369–4372.
(20) Chang, T. Polymer Characterization by Interaction
Chromatography. J. Polym. Sci. B 2005, 43, 1591–1607.
(21) Barnes, J. C.; Ehrlich, D. J. C.; Gao, A. X.; Leibfarth, F. A.;
Jiang, Y.; Zhou, E.; Jamison, T. F.; Johnson, J. A. Iterative Exponential
Growth of Stereo- and Sequence-Controlled Polymers. Nat. Chem.
2015, 7, 810–815.
(22) Jiang, Y.; Golder, M. R.; Nguyen, H. V.-T.; Wang, Y.; Zhong,
M.; Barnes, J. C.; Ehrlich, D. J. C.; Johnson, J. A. Iterative Exponential
Growth Synthesis and Assembly of Uniform Diblock Copolymers. J.
Am. Chem. Soc. 2016, 138, 9369–9372.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(23) Bidd, I.; Whiting, M. C. The synthesis of Pure n-Paraffins with
Chain-Lengths between One and Four Hundred. J. Chem. Soc. Chem.
Commun. 1985, 543–544.
(24) French, A. C.; Thompson, A. L.; Davis, B. G. High-Purity
Discrete PEG-Oligomer Crystals Allow Structural Insight. Angew.
Chem. Int. Ed. 2009, 48, 1248–1252.
(25) Takizawa, K.; Nulwala, H.; Hu, J.; Yoshinaga, K.; Hawker, C.
J. Molecularly Defined (L)-Lactic Acid Oligomers and Polymers:
Synthesis and Characterization. J. Polym. Sci. Part A: Polym. Chem.
2008, 46, 5977–5990.
(26) Takizawa, K.; Tang, C.; Hawker, C. J. Molecularly Defined
Caprolactone Oligomers and Polymers: Synthesis and Characterization.
J. Am. Chem. Soc. 2008, 130, 1718–1726.
(27) Koch, F. P. V.; Smith, P.; Heeney, M. “Fibonacci’s Route” to
Regioregular Oligo(3-hexylthiophene)s. J. Am. Chem. Soc. 2013, 135,
13695–13698.
(28) Lee, J. M.; Koo, M. B.; Lee, S. W.; Lee, H.; Kwon, J.; Shin. Y.
H.; Kim, S. Y.; Kim, K. T. High-Density Information Storage in an
Absolutely Defined Aperiodic Sequence of Monodisperse Copolyester.
Nat. Commun. 2020, 11, 56.
(29) Dodgson, K.; Sympson, D.; Semlyen, J. A. Studies of Cyclic
and Linear Poly(dimethyl siloxane): 2. Preparative Gel Permeation
Chromatography. Polymer 1978, 19, 1285–1288.
(34) Kricheldorf, H. R. Macrocycles. 21. Role of Ring–Ring
Equilibraia in Thermodynamically Controlled Polycondensations.
Macromolecules 2003, 36, 2302–2308.
(35) Suzuki, T.; Yamamoto, T.; Tezuka, Y. Constructing a
Macromolecular K3,3 Graph through Electrostatic Self-Assembly and
Covalent Fixation with a Dendritic Polymer Precursor. J. Am. Chem.
Soc. 2014, 136, 10148–10155.
(36) Dorgan, J. R.; Janzen, J.; Clayton, M. P.; Hait, B. S.; Knauss,
D. M. Melt Rheology of Variable L-content Poly(lactic acid). J.
Rheology 2005, 49, 607–619.
(37) Honda, S.; Yamamoto, T.; Tezuka, Y. Topology-Directed
Control on Thermal Stability: Micelles Formed from Linear and
Cyclized Amphiphilic Block Copolymers. J. Am. Chem. Soc. 2010,
132, 10251–10253.
(38) Zhang, B.; Zhang, H.; Li, Y.; Hoskins, J. N.; Grayson, S. M.
Exploring the Effect of Amphiphilic Polymer Architecture: Synthesis,
Characterization, and Self-Assembly of Both Cyclic and Linear
Poly(ethylene glycol)-b-polycaprolactone. ACS Macro Lett. 2013, 2,
845–848.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 6
1
2
3
TOC figure
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6
ACS Paragon Plus Environment