Letter pubs.acs.org/macroletters
Densely Packed Multicyclic Polymers Mikhail Gavrilov, Faheem Amir, Jakov Kulis, Md. D. Hossain, Zhongfan Jia, and Michael J. Monteiro* Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, Australia S Supporting Information *
ABSTRACT: Highly dense polymer chains were formed through coupling cyclic polymeric units in a sequence controlled manner. It was found that as the number of cyclic units increased the compactness substantially increased in a good solvent to a limiting value after only 12 units. This limiting value was close to that of a linear polymer chain in a θ solvent, in which polymer segment interactions with solvent are minimized. This remarkable result suggests that the unique architecture of the cyclic structure plays an important role to significantly change the polymer conformation and remain soluble in solution, which circumvents the need for crosslinking. The insight found in this work provides a physical mechanism as to why Nature uses cyclic structures in proteins to confer stability and the compacting of DNA strands to induce chromosome territories.
C
advantage of the ring-closure method is the ability to synthesize a wide range of cyclic polymer compositions and topologies.5,13 The probability of knots formed during ring closure are negligible under dilute conditions, in a good solvent14 and at the low molecular weights usually used (∼20 k).3 The nature and number of knots within a ring should, in principle, have a profound influence on the physical properties of the polymer within the melt. Nature has used cyclic peptides to confer stability and greater therapeutic efficacy15 through disulfide knots.16 Knots also drive mitochondrial DNA into loops or cycles along a central backbone, and this compact structure dominants in establishing chromosome territories within the nucleus17 by reducing their physical mixing due to their compact nature.18 Although territories play an important role in gene regulation, the precise nature of loops on the shape and compactness of such polymer molecules (e.g., chromosomes) is still unknown. We have recently shown that introducing knots into cyclic polystyrene increased the coil compactness and commensurately increased the glass transition temperature (Tg).5 Here, we used a new sequential synthetic technique developed in our group19 to produce polymer chains built from polystyrene cyclic macromers. The LND model allowed fits to the MWDs, and the coil dimensions as a function of backbone chain length were determined and correlated to the cyclic bottlebrush polymer’s solution and bulk glass transition properties. The nature of linking cyclic macromers together (see Scheme 1) should result in quite compact topologies compared to spiro and other cyclic topologies. We believe that the topology created with our new multicyclic polymers
yclic polymers exhibit different diffusion and viscoelastic properties compared to their linear analogues. Cyclic polymers have a more compact topology,1,2 which can be observed from the lower apparent number-average molecular weight (Mn,app) compared to the true Mn (Mn,abs) observed by size exclusion chromatography (SEC) using linear polystyrene standards as the calibration curve. The ratio of Mn,app/Mn,abs was found to be close to 0.75, which is close to that found theoretically of 0.71 for cyclic polystyrene.3 The hydrodynamic radius can be determined from SEC using the following equation: 3 = R h,sec
3KM na + 1 10πNA
(1)
where K = 0.0141 cm3 g−1, a = 0.7 (in a good solvent), NA is Avogadro’s number, and Mn is the number-average molecular weight found using a linear PSTY calibration curve. The K and a values used in this work were determined by light scattering for molecular weights ranging from 13000 to 2.2 × 106,4 which was in the range of molecular weights studied here. The relationship between the hydrodynamic volume contraction upon cyclization, gv = Vh,app/Vh,abs,5 and the ratio of Mn,app/ Mn,abs can be determined using eq 1. gv =
Vh,app Vh,abs
⎛ M n,app ⎞1.7 ⎟⎟ = ⎜⎜ ⎝ M n,abs ⎠
(2)
Synthetic cyclic polymers can be made either via the ringclosure6,7 or the ring expansion8 methods.9 Linear impurities have been found to influence the viscoelastic properties,10 and great efforts have been taken to remove residual linear polymers from the cyclic product through preparative size exclusion chromatography (SEC) with a quantitative analysis using the log-normal distribution (LND) fitting11 of the MWD.12 An © XXXX American Chemical Society
Received: August 3, 2017 Accepted: September 6, 2017
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DOI: 10.1021/acsmacrolett.7b00574 ACS Macro Lett. 2017, 6, 1036−1041
Letter
ACS Macro Letters Scheme 1. Synthetic Methodology for the Synthesis of Multicyclic Polystyrene by Sequence Control
Table 1. Size Exclusion Chromatography (SEC) of Controlled Sequential Cyclic Addition Fit Using the Log Normal Distribution (LND) Model to Determine the Coupling Efficiency and Hydrodynamic Coil Size and Contraction Volume (Eq 2) LND fit to RI-SECb
purity by LND (%) 3 4 6 7 8 9 10 11 12 13 14
polymer code
crude
prepped
coupling efficiency by LNDa (%)
Mn,app/Mn,abs
gv
(OH)-PSTY30-N3 c-PSTY30-OH c-PSTY30-N3 c-PSTY30-()OH (c-PSTY)2-OH (c-PSTY)2-N3 (c-PSTY)3-OH (c-PSTY)3-N3 (c-PSTY)4-OH (c-PSTY)4-N3 (c-PSTY)5-OH
91 98 93 94 >99 86 96 86 >99 88
>99
91
0.765
0.634
>99
94
0.77
0.641
96
89
0.739
0.598
95
91
0.69
0.532
93
0.656
0.488
a
CuAAC coupling efficiency was determined from the RI traces of SEC. Coupling efficiency calculated as follows: purity (LND)/max purity by theory × 100. bExperimental refractive index detector SEC (RI-SEC) traces were fit using the LND model by fitting Mn and Đ. The values of gv were calculated from eq 2.
was directly converted to the monocyclic 4, and after fractionation by preparative SEC, the purity of cyclic increased to >99% (Mn,app/Mn,abs = 0.765). The OH-group on 4 was converted to an azide 6, which after CuAAC “clicked” with a large excess of dialkyne linker (16) produced 7. The addition of 7 to 6 with direct azidation of the benzyl alcohol with DPPA and DBU19 allowed the sequential growth of a multicyclic polymer with up to 5 units (Scheme 1). The purity of the multicyclic after preparative SEC was greater than 99% for 2 units and decreased to 96% for units 3 and 4 (Table 1). Multicyclic 14 (with 5 monomer units) was produced with 88% purity immediately after the reaction and was not further purified due to the small amount of polymer available (
