RADICAL CASCADE-ENABLED SYNTHESIS OF PRECISION POLYMERS WITH COMPLEX MAIN-CHAIN STRUCTURES

FIELD OF THE INVENTION

The present invention is directed to the synthesis of precision polymers with complex main-chain structures.

BACKGROUND OF THE INVENTION

Radical cascade reactions have been widely applied in the synthesis of small molecules, in particular polycyclic structures. Eschenmoser, et al. and Stork and Burgstahler hypothesized that the biosynthesis of steroids occurred through a cascade of cyclization reactions from an acyclic squalene precursor (see Helv. Chim. Acta. (1955) 38:1890 and J. Am. Chem. Soc. (1955) 77:5068, respectively). Julia et al. reported the first radical dicyclization that involved a two-step radical cascade reaction to yield a bicyclic product from an acyclic α-cyano dienyl ester (see Bull. Soc. Chim. Fr. 1964, 1122; and Bull. Soc. Chim. Fr. 1964, 1129). To date a diverse array of examples of radical cascade reactions in organic chemistry have been reported, many of which feature kinetically-driven mechanisms that lead to products consisting of five- or six-membered rings.

Due to the synthetic accessibility and the propensity for the homolytic cleavage of the C—S bond under mild conditions, allyl sulfones were chosen as the core structure of the ring-opening trigger. Cho et al. (see Prog. Polym. Sci. (2000) 25:1043-1087) first reported the ring-opening polymerization of α-vinyl cyclic sulfones, but this early example relies on the relief of the ring strain as the driving force of the reaction, leading to in a limited scope of strained cyclic monomers. In addition, the sulfonyl radical resulted from ring opening cannot be deactivated/controlled in this system. Quiclet-Sire and Zard suggested that while in general the equilibrium favors the formation of the alkylsulfonyl radical, a reverse reaction to extrude SO₂can readily occur if the resulting alkyl radical is stabilized (see J. Am. Chem. Soc. (1996) 118:1209).

It should be noted that the cyclic allylic sulfide monomers developed are the only existing example to date of radical ROP of macrocyclic monomers (see Macromolecules (1994) 27:7935; Macromolecules (1996) 29:6983; and J. Am. Chem. Soc. (2009) 131:9805). However, the cyclic allylic sulfide monomers suffer from incomplete ring opening due to lack of driving force and the inability to deactivate the thiyl radical during chain propagation, resulting in low reactivity and difficulties in polymerization control. Gutekunst and Hawker have shown that a triggered ring-opening metathesis polymerization (ROMP) system based on olefin metathesis could allow ROMP of macrocyclic monomers by providing the thermodynamic driving force (see J. Am. Chem. Soc. 2015, 137:8038-8041).

Despite advances in polymerization research, particularly as it relates to ring-opening metathesis polymerization, there remains a need for synthesis methods directed to the preparation of precision polymers with complex main-chain structures that comprise broad functional group compatibility; amenable to preparation of a wide variety of well-defined copolymers, including block polymers, random copolymers, and the like; and having fast reaction kinetics and excellent chain end fidelity. These needs and other needs are satisfied by the present disclosure.

In addition, the well-defined copolymers, including block polymers, random copolymers, and the like; and the polymerization reaction with fast reaction kinetics and excellent chain end fidelity are important for producing degradable polymers as potential replacements for traditional vinyl plastics. Half of all plastics produced worldwide, annually, consist of vinyl polymers generated by radical polymerization. These contribute to a significant portion of the plastic waste accumulation in the environment. While much effort has been made to develop sustainable and degradable polymers as potential replacements (e.g., polyesters and polylactides) for traditional vinyl plastics, the material properties and the costs of these alternative polymers are often less competitive when compared to vinyl polymers in real world applications.

Unfavorable reactivity ratios in the copolymerization with vinyl monomers have been a major barrier for the existing radical ring-opening polymerization systems for the synthesis of degradable vinyl polymers. In these systems, a large excess of labile group-embedded cyclic monomers are required to incorporate appreciable amounts in the resulting copolymer due to the unfavorable reactivity ratios. Furthermore, their inability to control the reactivities in copolymerization also results in gradient or tapered distributions of labile functional groups in the backbone, significantly limiting the material properties of these polymers and also leading to partial degradation.

It would be desirable if labile functional groups could be evenly incorporated into the backbone of traditional vinyl polymers at high conversion in predictable and readily tunable ratios through radical copolymerization. Ideally, the material properties of the resulting vinyl (co)polymers would be readily tunable, allowing them to be both degradable and able to possess material properties comparable to traditional vinyl polymers. These needs and other needs are satisfied by the present disclosure.

SUMMARY OF THE INVENTION

In accordance with the purpose(s) of the disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to methods and compositions for radical cascade-enabled synthesis of precision polymers with complex main-chain structures.

Disclosed are compounds having a structure represented by a formula:

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wherein R¹is diyl group selected from —(C1-C16 alkanediyl)-O—(C═O)—R²⁰—(C═O)—O—(C1-C6 alkanediyl), —O—(C1-C16 alkanediyl)-O—, —O—(C1-C16 alkanediyl)-(C3-C12 cyclic alkanediyl)-(C1-C16 alkanediyl)-O—, —O—(C1-C16 alkanediyl)-(C3-C12 heterocyclic alkanediyl)-(C1-C16 alkanediyl)-O—, —O—(C1-C16 alkanediyl)(arylene)-(C1-C16 alkanediyl)-O—, —NH—(C1-C16 alkanediyl)-NH—, —NH—(C1-C16 alkanediyl)-(C3-C12 cyclic alkanediyl)-(C1-C16 alkanediyl)-NH—, —NH—(C1-C16 alkanediyl)-(C3-C12 heterocyclic alkanediyl)-(C1-C16 alkanediyl)-NH—, and —NH—(C1-C16 alkanediyl)-(arylene)-(C1-C16 alkanediyl)-NH—; wherein R²is an aryl group substituted with 1, 2, or 3 electron-withdrawing groups; wherein R³is selected from hydrogen, (C1-C16) alkyl, aryl, and heteroaryl; wherein R²⁰is selected from arylene, a (C1-C12)alkanediyl, and —R²¹—(C1-C16 alkanediyl)-R²²—; and wherein each occurrence of R²¹and R²²are independently an arylene.

Also disclosed are compounds having a structure represented by a formula:

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wherein R¹⁰is a group having a structure represented by a formula:

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wherein n is integer having a value of 1, 2, 3, 4, 5, or 6; and, wherein R¹¹is a group such as phenyl or a C2-C12 alkyl group. In some aspects, R¹¹is phenyl, ethyl, or —C12H₂₅.

Also disclosed are methods for preparing a polymer, the method comprising: reacting a compound having a structure represented by a formula:

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wherein R¹is diyl group selected from —(C1-C16 alkanediyl)-O—(C═O)—R²⁰—(C═O)—O—(C1-C6 alkanediyl), —O—(C1-C16 alkanediyl)-O—, —O—(C1-C16 alkanediyl)-(C3-C12 cyclic alkanediyl)-(C1-C16 alkanediyl)-O—, —O—(C1-C16 alkanediyl)-(C3-C12 heterocyclic alkanediyl)-(C1-C16 alkanediyl)-O—, —O—(C1-C16 alkanediyl)-(arylene)-(C1-C16 alkanediyl)-O—, —NH—(C1-C16 alkanediyl)-NH—, —NH—(C1-C16 alkanediyl)-(C3-C12 cyclic alkanediyl)-(C1-C16 alkanediyl)-NH—, —NH—(C1-C16 alkanediyl)-(C3-C12 heterocyclic alkanediyl)-(C1-C16 alkanediyl)-NH—, and —NH—(C1-C16 alkanediyl)-(arylene)-(C1-C16 alkanediyl)-NH—; wherein R²is an aryl group substituted with 1, 2, or 3 electron-withdrawing groups; wherein R³is selected from hydrogen, (C1-C16) alkyl, aryl, and heteroaryl; wherein R²⁰is selected from arylene, a (C1-C12)alkanediyl, and —R²¹—(C1-C16 alkanediyl)-R²²—; and wherein each occurrence of R²¹and R²²are independently an arylene; with a chain transfer agent in the presence of a compound having a structure represented by the formula:

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wherein R¹⁰is selected from a group having a structure represented by a formula:

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wherein n is integer having a value of 1, 2, 3, 4, 5, or 6; and, wherein R¹¹is a group selected from phenyl and a C2-C12 alkyl group.

Also disclosed are polymers prepared using the disclosed methods, the polymer having a structure given by the formula:

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Also disclosed are block copolymers prepared by the disclosed methods, the block copolymer having a structure given by a formula:

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Wherein each of R^1aand R^1bis diyl group independently selected from —(C1-C16 alkanediyl)-O—(C═O)—R²⁰—(C═O)—O—(C1-C6 alkanediyl), —O—(C1-C16 alkanediyl)-O—, —O—(C1-C16 alkanediyl)-(C3-C12 cyclic alkanediyl)-(C1-C16 alkanediyl)-O—, —O—(C1-C16 alkanediyl)-(C3-C12 heterocyclic alkanediyl)-(C1-C16 alkanediyl)-O—, —O—(C1-C16 alkanediyl)-(arylene)-(C1-C16 alkanediyl)-O—, —NH—(C1-C16 alkanediyl)-NH—, —NH—(C1-C16 alkanediyl)-(C3-C12 cyclic alkanediyl)-(C1-C16 alkanediyl)-NH—, —NH—(C1-C16 alkanediyl)-(C3-C12 heterocyclic alkanediyl)-(C1-C16 alkanediyl)-NH—, and —NH—(C1-C16 alkanediyl)-(arylene)-(C1-C16 alkanediyl)-NH—; wherein each of R^2aand R^2bis independently an aryl group substituted with 1, 2, or 3 electron-withdrawing groups; wherein R^1ais selected from hydrogen, (C1-C16) alkyl, aryl, and heteroaryl; wherein each of R^1aand R^3bis independently selected from arylene, a (C1-C12)alkanediyl, and —R²¹—(C1-C16 alkanediyl)-R²²—; wherein each occurrence of R²¹and R²²is independently an arylene; wherein R¹⁰is selected from a group having a structure represented by a formula:

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wherein n is integer having a value of 1, 2, 3, 4, 5, or 6; and, wherein R¹¹is a group selected from phenyl and a C2-C12 alkyl group.

In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in another aspect, relates to a method of preparing a polymer, the method including at least the steps of:

providing a compound of Formula I

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wherein R²is an aryl group substituted with 1, 2, or 3 electron-withdrawing groups;

wherein R³is selected from hydrogen, (C1-C16) alkyl, aryl, and heteroaryl;

wherein R²⁰is selected from arylene, a (C1-C12)alkanediyl, and —R²¹—(C1-C16 alkanediyl)-R²²—; and

wherein each of R²¹and R²²are independently an arylene; and

reacting the compound of Formula I in the presence of a photocatalyst and a chain transfer agent of Formula II or Formula III:

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wherein R¹⁰is selected from a group having a structure represented by a formula:

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wherein n is integer having a value of 1, 2, 3, 4, 5, or 6; and,

wherein R¹¹is a group selected from phenyl and a C2-C12 alkyl group.

In another aspect, the photocatalyst can be selected from

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or any combination thereof. In some aspects, the compound of Formula I, photocatalyst, and chain transfer agent can be irradiated with visible light such as, for example, light having a wavelength of 450 nm.

Still in another aspect, disclosed are polymers prepared by the above disclosed methods.

Other systems, methods, features, and advantages of the present disclosure will be or become apparent to one with skill in the art upon examination of the following drawings and detailed description. It is intended that all such additional systems, methods, features, and advantages be included within this description, be within the scope of the present disclosure, and be protected by the accompanying claims. In addition, all optional and preferred features and modifications of the described embodiments are usable in all aspects of the disclosure taught herein. Furthermore, the individual features of the dependent claims, as well as all optional and preferred features and modifications of the described embodiments are combinable and interchangeable with one another.

BRIEF DESCRIPTION OF THE FIGURES

The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present disclosure. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.

FIG. 1A shows a plot of molecular weights and dispersity versus monomer conversion. FIG. 1B shows MALDI analysis of P-4-3k. FIG. 1C shows SEC analysis of block copolymer P-5-b-P-4. FIG. 1D shows SEC analysis of block copolymer P-6-b-P-4.

FIG. 2 shows representative data pertaining to the degradation of the random copolymer P10 as determined by SEC analysis.

FIG. 3 shows representative NMR determination of monomer conversion for the polymerization of macrocyclic monomer 4. When Peak a (the methyl group of the polymer) is normalized to 1, the conversion is thus calculated as α=1/(1+0.90)×100%=53%.

FIG. 4 shows representative data for SEC analysis on the effect of different CTAs on the polymerization.

FIG. 5 shows representative data for SEC analysis on the effect of different solvent on the polymerization.

FIG. 6 shows representative data for SEC analysis on the effect of different concentration on the polymerization.

FIG. 7 shows representative data for SEC analysis on the effect of different ratio of CTA and AIBN on the polymerization.

FIG. 8 shows representative data for SEC analysis on the effect of temperature on the polymerization.

FIG. 9A shows a linear relationship between In([M]₀/[M]_t) and reaction time was observed. FIG. 9B shows SEC traces of different times.

FIG. 10 shows representative ¹H NMR data obtained for polymer P-4-3k. The structure of the compound is shown as an inset, with the structures identified with letters corresponding to the labeled peaks in the ¹H NMR data.

FIG. 11 shows representative MALDI-TOF data obtained for polymer P-4-3k.

FIG. 12 shows representative ¹H NMR data obtained for a disclosed random copolymer. The peak a corresponds to the methyl group of macrocyclic repeat units, and the peak b corresponds to methyl group of methyl acrylate repeat units. When peak a is normalized to 1, the mole % of macrocyclic repeat units is thus calculated as 1/(1+7.10)×100%=12%.

FIG. 13 shows representative ¹H NMR data obtained for methanolysis of P10. T=0: all peaks in the starting polymer were broad; T=10 seconds: variety of oligomeric and small molecule species were found indicated by the emergence of sharp peaks (red circles); T=10 min: the ester peaks of polymer backbone disappeared (indicated by the black arrow) and most peaks are sharp, indicating the small hydrolysis fragments.

FIG. 14A shows a prior art radical polymerization reaction mechanism for polymerization of acyclic acrylic monomers. FIG. 14B shows a prior art radical polymerization reaction mechanism for polymerization of strained cyclic monomers. FIG. 14C shows a representative reaction mechanism of a disclosed RCT-ROP of macrocyclic monomers with low ring strain.

FIG. 15A shows a first reaction mechanism as shown. FIG. 15B shows a second reaction mechanism as shown. FIG. 15C shows a third reaction mechanism as shown. FIG. 15D shows a fourth reaction mechanism as shown.

FIGS. 16A-16B show reactions for: trigger-testing Compound 1 as shown in FIG. 16A; and the macrocyclic monomers 4-7 (numbers in the structure indicate ring size) as shown in FIG. 16B.

FIG. 17A shows a representative reaction for the free radical polymerization of 1,6-diene monomer 8; and FIG. 17B representative SEC analysis data of the free radical polymerization of 1,6-diene monomer 8 reaction shown in FIG. 17A.

FIG. 18A shows the radical cascade reaction of the trigger-testing compound 9 to provide compound 10; FIG. 18B shows representative data obtained for compound 10; and FIG. 18C shows summary data for the reaction.

FIG. 19A shows a representative radical cascade-triggered ring-opening polymerization of the macrocyclic monomer 11 in the absence of 2-(((ethylthio)carbonothioyl)thio)-2-methylpropanoic acid; FIG. 19B shows a representative radical cascade-triggered ring-opening polymerization of the macrocyclic monomer 11 in the presence of 2-(((ethylthio)carbonothioyl)thio)-2-methylpropanoic acid; and FIG. 19C shows representative SEC analysis data.

FIG. 20A shows the reaction for a radical cascade ring-closing polymerization reaction for monomer 12. FIG. 20B shows representative NMR data collected for the reaction.

FIG. 21 shows a representative reaction for light-mediated ring-opening cascade polymerization using fac-Ir(ppy)₃as photoredox catalyst.

FIG. 22 shows representative data for a kinetic study on the polymerization of macrocyclic monomer 7. The experiment was performed at the following condition: 18 W blue LED light (λ_max=450 nm), [M]: [CTA]: [photocatalyst]=50:1:0.01, initial monomer concentration [M]₀=0.2 M, 25° C. under argon in a sealed 4 mL vial. A linear relationship between In([M]₀/[M]_t) and reaction time is observed at early stage. The plot deviates from the linear relationship with time after In([M]₀-[M]_t) has reached to 0.4.

FIG. 23 shows representative data for a plot of M_n(g/mol) and D versus monomer conversion. The experiment was performed at the following condition: 18 W blue LED light (λ_max=450 nm), [M]: [CTA]: [photocatalyst]=50:1:0.01, initial monomer concentration [M]₀=0.2 M, 25° C. under argon in a sealed 4 mL vial. The linear relationship between molecular weights (M_n) and monomer conversion shows excellent control during chain growth. The dispersity ( custom-character ) can remain as low as 1.15 even at 70% conversion.

FIG. 24 shows representative data for overlay of SEC traces of different conversion. The experiment was performed at the following condition: 18 W blue LED light (λ_max=450 nm), [M]: [CTA]: [photocatalyst]=50:1:0.01, initial monomer concentration [M]₀=0.2 M, 25° C. under argon in a sealed 4 mL vial. As a support for FIG. 23, the overlay SEC traces of different conversion clearly illustrates the retention time of each curve gradually decreases as the monomer conversion increases.

FIG. 25 shows representative data for In([M]₀/[M]_t) vs time with intermittent light exposure. Plot of In([M]₀/[M]_t) versus time clearly demonstrates that polymerization proceeds only in the presence of light.

FIGS. 26A and 26C show representative data for the temperature effect between polymerization of methyl acrylate (MA) shown in FIG. 26B and the polymerization of macrocyclic monomer 7 shown in FIG. 26C. The In([M]₀/[M]_t) versus time is plotted for polymerization of methyl acrylate (MA) and macrocyclic monomer 7 at different temperatures is shown in FIG. 26A. The plot clearly shows temperature has higher influence towards polymerization of monomer 7 than that of MA.

FIG. 27 provides a representative mechanism investigation by DFT calculation. All geometries are optimized using B3LYP/6-31G* method. No solvation is considered. All energies are Gibbs free energies computed at 1 atm and 298K.

FIG. 28 provides a molecular structure for compound 4 represented using a ball-and-stick model.

FIG. 29 shows DSC thermograms of polymers recorded under argon during the second cooling cycle at a heating rate of 10° C./min.

FIG. 30 shows TGA thermograms of polymers recorded under argon at a heating rate of 10° C./min.

FIG. 31A shows kinetic plots of In([M]₀/[M]_t) versus reaction time, where [M]₀is the initial monomer concentration and [M]_tis the monomer concentration at a given time t. FIG. 31B shows plots of M_nand custom-character as a function of monomer conversion. FIG. 31C shows MALDI-TOF analysis of P-1-5k. The spacing between these discrete oligomers was consistent with the expected mass of the repeating unit (344 g/mol). Each peak corresponds to a discrete oligomer that consists of the α- and ω-chain end, the number of repeating units multiplied by its molar mass, and a sodium cation. FIG. 31D shows ¹H-NMR spectroscopy of P-1-6k. FIG. 31E shows chain extension of P-2-4k by 1. FIG. 31F shows SEC analysis of block copolymer P-2-b-P-1. FIG. 31G shows In([M]₀/[M]_t) vs. reaction time with intermittent light exposure.

FIG. 32 shows ¹H NMR determination of monomer conversion for polymerization of allylic sulfone macrocyclic monomer 1.

FIG. 33 shows ¹H NMR determination of degree of polymerization of purified P-1.

FIG. 34A shows kinetic plots of In([M]₀/[M]_t) versus reaction time of both comonomers. FIG. 34B shows plots of M_nand incorporation of monomer 1 (F₁) as a function of total conversion. FIG. 34C shows that the plot of total conversion with respect to [1(t)]/[1(0)] is fitted to Eq 2 and Eq 3 of the BSL model to derive the reactivity ratios. FIG. 34D shows the reactivity ratios of monomer 1 and MA in the photocontrolled radical copolymerization remained close to unity in a broad range of monomer feed compositions. FIG. 34E shows that the T_gof the (co)polymer P-(1-co-MA) could be fine-tuned by the initial comonomer feed composition. FIG. 34F shows degradation of P-(1-co-MA) generated by the thermally initiated radical copolymerization (F₁^(end)=0.08) and the photocontrolled copolymerization (F₁^(end)=0.10), respectively.

FIG. 35A shows compositional analysis of the copolymers P-1-co-MA at f₁⁰=0.05 at different time points of the reaction by ¹H-NMR. FIG. 35B shows compositional analysis of the copolymers P-1-co-MA at f₁⁰=0.09 at different time points of the reaction by ¹H-NMR, FIG. 35C shows compositional analysis of the copolymers P-1-co-MA at f₁⁰=0.17 at different time points of the reaction by ¹H-NMR. FIG. 35D shows compositional analysis of the copolymers P-1-co-MA at f₁⁰=0.50 at different time points of the reaction by ¹H-NMR.

FIG. 35E shows compositional analysis of the copolymers P-1-co-MA at f₁⁰=0.67 at different time points of the reaction by ¹H-NMR.

FIG. 36A shows that the plot of total conversion with respect to [1(t)]/[1(0)] is fitted to the BSL model to derive the comonomer reactivity ratios for copolymerization of monomer 1 and MA at f₁⁰=0.09 at 25° C. FIG. 36B shows that the plot of total conversion with respect to [1(t)]/[1(0)] is fitted to the BSL model to derive the conomomer reactivity ratios for copolymerization of monomer 1 and MA at f₁⁰=0.17 at 25° C. FIG. 36C shows that the plot of total conversion with respect to [1(t)]/[1(0)] is fitted to the BSL model to derive the conomomer reactivity ratios for copolymerization of monomer 1 and MA at f₁⁰=0.50 at 25° C.

FIG. 36D shows that the plot of total conversion with respect to [1(t)]/[1(0)] is fitted to the BSL model to derive the conomomer reactivity ratios for copolymerization of monomer 1 and MA at f₁⁰=0.67 at 25° C.

FIG. 37A shows kinetics of photocontrolled rROCP copolymerization of monomer 1 and MA at f₁⁰=0.09 at 25° C. FIG. 37B shows kinetics of photocontrolled rROCP copolymerization of monomer 1 and MA at f₁⁰=0.17 at 25° C. FIG. 37C shows kinetics of photocontrolled rROCP copolymerization of monomer 1 and MA at f₁⁰=0.50 at 25° C. FIG. 37D shows kinetics of the photocontrolled rROCP copolymerization of monomer 1 and MA at f₁⁰=0.67 at 25° C.

FIG. 38 shows kinetics of the photocontrolled rROCP copolymerization of monomer 1 and tBA at f₁⁰=0.09 at 25° C.

FIG. 39 shows kinetics of the photocontrolled rROCP copolymerization of monomer 1 and DMA at f₁⁰=0.09 at 25° C.

FIG. 40 shows compositional analysis of the copolymers P-1-co-tBA at f₁⁰=0.09 at different time points of the reaction by ¹H-NMR.

FIG. 41 shows compositional analysis of the copolymers P-1-co-BnA at f₁⁰=0.09 at different time points of the reaction by ¹H-NMR.

FIG. 42 shows compositional analysis of the copolymers P-1-co-DMA at f₁⁰=0.09 at different time points of the reaction by ¹H-NMR.

FIG. 43 shows that the plot of total conversion with respect to [1(t)]/[1(0)] is fitted to the BSL model to derive the comonomer reactivity ratios for copolymerization of 1 and BnA at f₁⁰=0.09 at 25° C.

FIG. 44 shows that the plot of total conversion with respect to [1(t)]/[1(0)] is fitted to the BSL model to derive the comonomer reactivity ratios for copolymerization of monomer 1 and tBA at f₁⁰=0.09 at 25° C.

FIG. 45 shows that the plot of total conversion with respect to [1(t)]/[1(0)] is fitted to the BSL model to derive the comonomer reactivity ratios for copolymerization of monomer 1 and DMA at f₁⁰=0.09 at 25° C.

FIGS. 46A-46C show generation of degradable nanoparticles via PISA. FIG. 46A shows a scheme of the triblock copolymer nanoparticle synthesis and degradation. FIG. 46B shows TEM image of the nanoparticles formed via PISA. FIG. 46C shows TEM image of the nanoparticles after NaOH treatment at 50° C. The large aggregates are the insoluble PtBA fragments after nanoparticle degradation.

FIG. 47 shows SEC analysis of block copolymer mPEG₁₀₀-b-P-1.

FIG. 48 shows SEC analysis of nanoparticle mPEG₁₀₀-b-P-1-b-PtBA. The broad dispersity of the final PtBA block is likely caused by the aggregation of the triblock copolymer as it was being formed.

FIG. 49 shows degradation of nanoparticle mPEG₁₀₀-b-P-1-b-PtBA. The two peaks in the SEC trace of the degraded copolymer correspond to the PtBA and mPEG fragments, respectively.

FIG. 50A shows that SO₂is hypothesized to inhibit chain propagation by recombining with the propagating radical. M denotes monomers. FIG. 50B shows DFT calculations. FIG. 50C shows EPR studies of photocontrolled rROCP. The experimental results are shown as solid lines. The simulated EPR spectra based on the hypothesized composition of the reaction mixture at different stages of the reaction are shown as dotted lines. The experimental EPR spectra are well aligned with the simulated ones. Spectrum I: early stage of polymerization (first two hours). Spectrum II: Late stage of polymerization (after five hours). Spectrum III: Injection of exogenous SO₂at early stage of polymerization.

FIG. 51 shows mechanistic investigation of the cascade process of the photocontrolled rROCP by DFT calculations.

FIG. 52A shows argon sparging at 25° C. improved the reaction rate in the late stage of rROCP. FIG. 52B shows that argon sparging at 25° C. improved the reaction rate in the late stage of the copolymerization of 1 and BnA at f₁⁰=0.09. FIG. 52C shows that elevating temperature to 50° C. plus argon sparging led to further improved reaction rate. FIG. 52D shows alternating Ar and SO₂gas introduced into the reaction at 50° C.

FIG. 53 shows kinetics of photocontrolled rROCP homopolymerization of monomer 1 at 25° C. and 50° C. in a sealed vial.

FIG. 54 shows kinetics of photocontrolled rROCP homopolymerization of monomer 1 under different temperatures with Ar bubbling.

FIG. 55 shows kinetics of the photocontrolled rROCP copolymerization of monomer 1 and MA at f₁⁰=0.09 at 50° C.

FIG. 56 shows that the plot of total conversion with respect to [1(t)]/[1(0)] is fitted to the BSL model to derive the comonomer reactivity ratios for copolymerization of 1 and MA at f₁⁰=0.09 at 50° C.

FIG. 57 shows alternating introduction of Ar and SO₂gas to the photocontrolled rROCP homopolymerization of 1 at 25° C.

FIG. 58 shows ¹H NMR analysis of random copolymerization of allylic sulfone macrocyclic monomer 1 (aka “compound 7”) and MA. The incorporation of 1 in the copolymer (F₁) remained identical to f throughout the copolymerization.

FIG. 59A and FIG. 59B show NMR of monomer 1.

FIG. 60A and FIG. 60B show NMR of monomer 4.

FIG. 61A and FIG. 61B show NMR of monomer 3.

FIG. 62A and FIG. 62B show NMR of P-1.

FIG. 63A and FIG. 63B show NMR of P-2.

FIG. 64A and FIG. 64B provide NMR of P-3.

FIG. 65A and FIG. 65B provide NMR of P-2-b-P-1.

FIG. 66A shows NMR of P-(1-co-MA) at f₁⁰=0.05. FIG. 66B shows NMR of P-(1-co-MA) at f₁⁰=0.09. FIG. 66C shows NMR of P-(1-co-MA) at f₁⁰=0.17. FIG. 66D shows NMR of P-(1-co-MA) at f₁⁰=0.50. FIG. 66E shows NMR of P-(1-co-MA) at f₁⁰=0.67.

FIG. 67 provides NMR of P-(1-co-tBA) at f₁⁰=0.09.

FIG. 68 provides NMR of P-(1-co-BnA) at f₁⁰=0.09.

FIG. 69 provides NMR of P-(1-co-DMA) at f₁⁰=0.09.

FIG. 70 shows TGA thermograms of copolymers P-(1-co-MA) with different compositions recorded under argon at a heating rate of 10° C./min.

Additional advantages of the disclosure will be set forth in part in the description which follows, and in part will be obvious from the description, or can be learned by practice of the disclosure. The advantages of the disclosure will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosure, as claimed.

DETAILED DESCRIPTION OF THE INVENTION

Many modifications and other embodiments disclosed herein will come to mind to one skilled in the art to which the disclosed compositions and methods pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be understood that the disclosures are not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. The skilled artisan will recognize many variants and adaptations of the aspects described herein. These variants and adaptations are intended to be included in the teachings of this disclosure and to be encompassed by the claims herein.

Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present disclosure.

Any recited method can be carried out in the order of events recited or in any other order that is logically possible. That is, unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification.

All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided herein can be different from the actual publication dates, which can require independent confirmation.

While aspects of the present disclosure can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present disclosure can be described and claimed in any statutory class.

It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed compositions and methods belong. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly defined herein.

Prior to describing the various aspects of the present disclosure, the following definitions are provided and should be used unless otherwise indicated. Additional terms may be defined elsewhere in the present disclosure.

A. DEFINITIONS

As used herein, “comprising” is to be interpreted as specifying the presence of the stated features, integers, steps, or components as referred to, but does not preclude the presence or addition of one or more features, integers, steps, or components, or groups thereof. Moreover, each of the terms “by”, “comprising,” “comprises”, “comprised of,” “including,” “includes,” “included,” “involving,” “involves,” “involved,” and “such as” are used in their open, non-limiting sense and may be used interchangeably. Further, the term “comprising” is intended to include examples and aspects encompassed by the terms “consisting essentially of” and “consisting of.” Similarly, the term “consisting essentially of” is intended to include examples encompassed by the term “consisting of.

As used herein, nomenclature for compounds, including organic compounds, can be given using common names, IUPAC, IUBMB, or CAS recommendations for nomenclature. When one or more stereochemical features are present, Cahn-Ingold-Prelog rules for stereochemistry can be employed to designate stereochemical priority, E/Z specification, and the like. One of skill in the art can readily ascertain the structure of a compound if given a name, either by systemic reduction of the compound structure using naming conventions, or by commercially available software, such as CHEMDRAW™ (Cambridgesoft Corporation, U.S.A.).

As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a monomer,” “a polymer,” or “a chain transfer agent,” includes, but is not limited to, two or more such monomers, polymers, chain transfer agents, and the like, including a plurality of such monomers, polymers, chain transfer agents, and the like.

It should be noted that ratios, concentrations, amounts, and other numerical data can be expressed herein in a range format. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms a further aspect. For example, if the value “about 10” is disclosed, then “10” is also disclosed.

When a range is expressed, a further aspect includes from the one particular value and/or to the other particular value. For example, where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure, e.g. the phrase “x to y” includes the range from ‘x’ to ‘y’ as well as the range greater than ‘x’ and less than ‘y’. The range can also be expressed as an upper limit, e.g. ‘about x, y, z, or less’ and should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of ‘less than x’, less than y′, and ‘less than z’. Likewise, the phrase ‘about x, y, z, or greater’ should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of ‘greater than x’, greater than y′, and ‘greater than z’. In addition, the phrase “about ‘x’ to ‘y’”, where ‘x’ and ‘y’ are numerical values, includes “about ‘x’ to about ‘y’”.

It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a numerical range of “about 0.1% to 5%” should be interpreted to include not only the explicitly recited values of about 0.1% to about 5%, but also include individual values (e.g., about 1%, about 2%, about 3%, and about 4%) and the sub-ranges (e.g., about 0.5% to about 1.1%; about 5% to about 2.4%; about 0.5% to about 3.2%, and about 0.5% to about 4.4%, and other possible sub-ranges) within the indicated range.

As used herein, the terms “about,” “approximate,” “at or about,” and “substantially” mean that the amount or value in question can be the exact value or a value that provides equivalent results or effects as recited in the claims or taught herein. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and/or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art such that equivalent results or effects are obtained. In some circumstances, the value that provides equivalent results or effects cannot be reasonably determined. In such cases, it is generally understood, as used herein, that “about” and “at or about” mean the nominal value indicated ±10% variation unless otherwise indicated or inferred. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about,” “approximate,” or “at or about” whether or not expressly stated to be such. It is understood that where “about,” “approximate,” or “at or about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise.

As used herein, the term “effective amount” refers to an amount that is sufficient to achieve the desired modification of a physical property of the composition or material. For example, an “effective amount” of an monomer refers to an amount that is sufficient to achieve the desired improvement or effect modulated by indicated component, material, compound or polymer, e.g. achieving the desired molecular weight and/or percent yield in a synthesis reaction. The specific level in terms of concentration or amount as an effective amount will depend upon a variety of factors such as other compounds in the chemical reaction, temperature, concentration, and the like.

Reference to “a/an” chemical compound, monomer, and polymer each refers to one or more molecules of the chemical compound, monomer, and polymer rather than being limited to a single molecule of the chemical compound, monomer, and polymer. Furthermore, the one or more molecules may or may not be identical, so long as they fall under the category of the chemical compound, monomer, and polymer. Thus, for example, “a” polymer is interpreted to include one or more polymer molecules of the polymer, where the polymer molecules may or may not be identical, e.g., each having a characteristic molecular weight associated with an individual polymer molecule, such the entirety of polymer molecules has a molecular weight, such as a number average molecular weight representative of the population.

As used herein, the term “electron withdrawing group” means a chemical substituent that draws electrons to it. That is, a specific group that makes the electron density of the parent molecule unevenly distributed when it is attached to the parent molecule. An electron-withdrawing group pulls the electron from the parent molecule toward this group. Specifically, the term electron withdrawing group as used herein includes halides, nitro, trifluoromethyl, CN (nitriles), and carbonyl and derivatives such as COOH (carboxylic acids) and CONH₂(amides). More examples of electron-withdrawing groups can be found in March, Advanced Organic Chemistry, 4th, Wiley Interscience, 1992.

As used herein, the terms “optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

The term “alkyl” as used herein is a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, s-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, and the like. The alkyl group can be cyclic or acyclic. The alkyl group can be branched or unbranched. The alkyl group can also be substituted or unsubstituted. For example, the alkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, nitrile, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol, as described herein. A “lower alkyl” group is an alkyl group containing from one to six (e.g., from one to four) carbon atoms. The term alkyl group can also be a C1 alkyl, C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl, and the like up to and including a C1-C24 alkyl.

The term alkanediyl refers to branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms bound by two different carbon atoms to the respective substituents. That is, unless particularly stated otherwise, the term alkanediyl as used herein means a divalent atomic group obtained by extracting two hydrogen atoms from a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms. The alkanediyl group can be cyclic or acyclic. The alkanediyl group can be branched or unbranched. The alkyl group can also be substituted or unsubstituted. For example, the alkanediyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, nitrile, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol, as described herein. A “lower alkanediyl” group is an alkanediyl group containing from one to six (e.g., from one to four) carbon atoms. The term alkanediyl group can also be a C1 alkanediyl, C1-C2 alkanediyl, C1-C3 alkanediyl, C1-C4 alkanediyl, C1-C5 alkanediyl, C1-C6 alkanediyl, C1-C7 alkanediyl, C1-C8 alkanediyl, C1-C9 alkanediyl, C1-C10 alkanediyl, and the like up to and including a C1-C24 alkanediyl.

This practice is also used for other groups described herein. That is, while a term such as “cycloalkyl” refers to both unsubstituted and substituted cycloalkyl moieties, the substituted moieties can, in addition, be specifically identified herein; for example, a particular substituted cycloalkyl can be referred to as, e.g., an “alkylcycloalkyl.” Similarly, a substituted alkoxy can be specifically referred to as, e.g., a “halogenated alkoxy,” a particular substituted alkenyl can be, e.g., an “alkenylalcohol,” and the like. Again, the practice of using a general term, such as “cycloalkyl,” and a specific term, such as “alkylcycloalkyl,” is not meant to imply that the general term does not also include the specific term.

The term “cycloalkyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and the like. The term “heterocycloalkyl” is a type of cycloalkyl group as defined above, and is included within the meaning of the term “cycloalkyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkyl group and heterocycloalkyl group can be substituted or unsubstituted. The cycloalkyl group and heterocycloalkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as described herein. In one aspect, the heterocycloalkyl group can be a lactam, including but not limited to an N-substituted lactam.

As used herein, the term, “cycloalkanediyl” refers to a divalent atomic group obtained by extracting two hydrogen atoms from a cycloalkane, i.e., a non-aromatic carbon-based ring composed of at least three carbon atoms. The cycloalkanediyl group can be substituted or unsubstituted. The cycloalkanediyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as known to the skilled artisan.

As used herein, the term, “arylene” refers to divalent aromatic groups having in the range of 3 up to 14 carbon atoms (and optionally one or more heteroatoms such as N, S or O), and “substituted arylene” refers to arylene groups further bearing one or more substituents as set forth above.

The term “carboxylic acid” as used herein is represented by the formula —C(O)OH.

The term “ester” as used herein is represented by the formula —OC(O)A¹or —C(O)OA¹, where A¹can be alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “polyester” as used herein is represented by the formula -(A¹O(O)C-A²-C(O)O)_a— or -(A¹O(O)C-A²-OC(O))_a—, where A¹and A²can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein and “a” is an integer from 1 to 500. “Polyester” is as the term used to describe a group that is produced by the reaction between a compound having at least two carboxylic acid groups with a compound having at least two hydroxyl groups.

The terms “halo,” “halogen” or “halide,” as used herein can be used interchangeably and refer to F, Cl, Br, or I.

The term “heteroaryl” as used herein refers to an aromatic group that has at least one heteroatom incorporated within the ring of the aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus, where N-oxides, sulfur oxides, and dioxides are permissible heteroatom substitutions. The heteroaryl group can be substituted or unsubstituted. The heteroaryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as described herein. Heteroaryl groups can be monocyclic, or alternatively fused ring systems. Heteroaryl groups include, but are not limited to, furyl, imidazolyl, pyrimidinyl, tetrazolyl, thienyl, pyridinyl, pyrrolyl, N-methylpyrrolyl, quinolinyl, isoquinolinyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridazinyl, pyrazinyl, benzofuranyl, benzodioxolyl, benzothiophenyl, indolyl, indazolyl, benzimidazolyl, imidazopyridinyl, pyrazolopyridinyl, and pyrazolopyrimidinyl. Further not limiting examples of heteroaryl groups include, but are not limited to, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiophenyl, pyrazolyl, imidazolyl, benzo[d]oxazolyl, benzo[d]thiazolyl, quinolinyl, quinazolinyl, indazolyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazolyl, and pyrido[2,3-b]pyrazinyl.

The term “heterocycle” as used herein can be used interchangeably and refer to single and multi-cyclic aromatic or non-aromatic ring systems in which at least one of the ring members is other than carbon. Thus, the term is inclusive of, but not limited to, “heterocycloalkyl,” “heteroaryl,” “bicyclic heterocycle,” and “polycyclic heterocycle.” Heterocycle includes pyridine, pyrimidine, furan, thiophene, pyrrole, isoxazole, isothiazole, pyrazole, oxazole, thiazole, imidazole, oxazole, including, 1,2,3-oxadiazole, 1,2,5-oxadiazole and 1,3,4-oxadiazole, thiadiazole, including, 1,2,3-thiadiazole, 1,2,5-thiadiazole, and 1,3,4-thiadiazole, triazole, including, 1,2,3-triazole, 1,3,4-triazole, tetrazole, including 1,2,3,4-tetrazole and 1,2,4,5-tetrazole, pyridazine, pyrazine, triazine, including 1,2,4-triazine and 1,3,5-triazine, tetrazine, including 1,2,4,5-tetrazine, pyrrolidine, piperidine, piperazine, morpholine, azetidine, tetrahydropyran, tetrahydrofuran, dioxane, and the like. The term heterocyclyl group can also be a C2 heterocyclyl, C2-C3 heterocyclyl, C2-C4 heterocyclyl, C2-C5 heterocyclyl, C2-C6 heterocyclyl, C2-C7 heterocyclyl, C2-C8 heterocyclyl, C2-C9 heterocyclyl, C2-C10 heterocyclyl, C2-C11 heterocyclyl, and the like up to and including a C2-C18 heterocyclyl. For example, a C2 heterocyclyl comprises a group which has two carbon atoms and at least one heteroatom, including, but not limited to, aziridinyl, diazetidinyl, dihydrodiazetyl, oxiranyl, thiiranyl, and the like. Alternatively, for example, a C5 heterocyclyl comprises a group which has five carbon atoms and at least one heteroatom, including, but not limited to, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, diazepanyl, pyridinyl, and the like. It is understood that a heterocyclyl group may be bound either through a heteroatom in the ring, where chemically possible, or one of carbons comprising the heterocyclyl ring.

The term “bicyclic heterocycle” as used herein refers to a ring system in which at least one of the ring members is other than carbon. Bicyclic heterocyclyl encompasses ring systems wherein an aromatic ring is fused with another aromatic ring, or wherein an aromatic ring is fused with a non-aromatic ring. Bicyclic heterocyclyl encompasses ring systems wherein a benzene ring is fused to a 5- or a 6-membered ring containing 1, 2 or 3 ring heteroatoms or wherein a pyridine ring is fused to a 5- or a 6-membered ring containing 1, 2 or 3 ring heteroatoms. Bicyclic heterocyclic groups include, but are not limited to, indolyl, indazolyl, pyrazolo[1,5-a]pyridinyl, benzofuranyl, quinolinyl, quinoxalinyl, 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, 3,4-dihydro-2H-chromenyl, 1H-pyrazolo[4,3-c]pyridin-3-yl; 1H-pyrrolo[3,2-b]pyridin-3-yl; and 1H-pyrazolo[3,2-b]pyridin-3-yl.

The term “heterocycloalkyl” as used herein refers to an aliphatic, partially unsaturated or fully saturated, 3- to 14-membered ring system, including single rings of 3 to 8 atoms and bi- and tricyclic ring systems. The heterocycloalkyl ring-systems include one to four heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein a nitrogen and sulfur heteroatom optionally can be oxidized and a nitrogen heteroatom optionally can be substituted. Representative heterocycloalkyl groups include, but are not limited to, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, and tetrahydrofuryl.

The term “nitro” as used herein is represented by the formula —NO₂.

The term “nitrile” or “cyano” as used herein is represented by the formula —CN.

The term “thiol” as used herein is represented by the formula —SH.

As described herein, compounds of the invention may contain “optionally substituted” moieties. In general, the term “substituted,” whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds. In is also contemplated that, in certain aspects, unless expressly indicated to the contrary, individual substituents can be further optionally substituted (i.e., further substituted or unsubstituted).

Compounds described herein comprise atoms in both their natural isotopic abundance and in non-natural abundance. The disclosed compounds can be isotopically-labeled or isotopically-substituted compounds identical to those described, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, sulfur, fluorine and chlorine, such as ²H, ³H, ¹³O, ¹⁴O, ¹⁵N, ¹⁸O, ¹⁷O, ³⁵S, ¹⁸F, and ³⁶Cl, respectively. Compounds further comprise prodrugs thereof and pharmaceutically acceptable salts of said compounds or of said prodrugs which contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically-labeled compounds of the present invention, for example those into which radioactive isotopes such as ³H and ¹⁴O are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i.e., ³H, and carbon-14, i.e., ¹⁴C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., ²H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. Isotopically labeled compounds of the present invention and prodrugs thereof can generally be prepared by carrying out the procedures below, by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent.

In some aspects, a structure of a compound can be represented by a formula:

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which is understood to be equivalent to a formula:

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wherein n is typically an integer. That is, Rⁿis understood to represent five independent substituents, R^n(a), R^n(b), R^n(c), R^n(d), and R^n(e). By “independent substituents,” it is meant that each R substituent can be independently defined. For example, if in one instance R^n(a)is halogen, then R^n(b)is not necessarily halogen in that instance.

Certain materials, compounds, compositions, and components disclosed herein can be obtained commercially or readily synthesized using techniques generally known to those of skill in the art. For example, the starting materials and reagents used in preparing the disclosed compounds and compositions are either available from commercial suppliers such as Aldrich Chemical Co., (Milwaukee, Wis.), Acros Organics (Morris Plains, N.J.), Fisher Scientific (Pittsburgh, Pa.), or Sigma (St. Louis, Mo.) or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Compounds, Volumes 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991); March's Advanced Organic Chemistry, (John Wiley and Sons, 4th Edition); and Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989).

As used herein, “weight average molecular weight” or Mw is an average molecular weight that takes the molecular weight of a chain into account when determining contribution to the molecular weight average. Thus, a longer polymer chain will contribute more to Mw than will a shorter polymer chain.

As used herein, “number average molecular weight” or Mn refers to the statistical average molecular weight of all polymer chains in a sample. In one aspect, Mn can be predicted by polymerization mechanism. In another aspect, for a given Mn, equal numbers of molecules exist on either side of Mn in the molecular weight distribution.

As used herein, “dispersity” or “polydispersity index” is a measure of the heterogeneity of sizes of polymers in a composition. Dispersity is represented by the symbol custom-character , where =Mw/Mn. will always be greater than or equal to 1, but will be larger for polymer chains with widely varying chain lengths and will be closer to 1 for polymer chains with uniform chain length.

Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including: matters of logic with respect to arrangement of steps or operational flow; plain meaning derived from grammatical organization or punctuation; and the number or type of embodiments described in the specification.

The following abbreviations and acronyms are used herein throughout: “CTA” refers to “chain transfer agents”; “HPLC” refers to “high pressure liquid chromatography”; “LC” refers to “liquid chromatography” “MALDI” refers to “matrix-assisted laser desorption/ionization”; “MS” refers to mass spectrometry; “NMR” refers to “nuclear magnetic resonance”, such as nuclear magnetic resonance spectroscopy; “RCT” refers to “radical cascade-triggered”; “ROMP” refers to “ring-opening metathesis polymerization”; “ROP” refers to “ring opening polymerization”; “SEC” refers to “size exclusion chromatography”; “rROCP” refers to radical ring-opening cascade polymerization, “PISA” refers to polymerization-induced self-assembly, and “TOF” refers to “time-of-flight”.

Disclosed are the components to be used to prepare the compositions of the invention as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds cannot be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules including the compounds are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the compositions of the invention. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the methods of the invention.

It is understood that the compositions disclosed herein have certain functions. Disclosed herein are certain structural requirements for performing the disclosed functions, and it is understood that there are a variety of structures that can perform the same function that are related to the disclosed structures, and that these structures will typically achieve the same result.

Unless otherwise specified, temperatures referred to herein are based on atmospheric pressure (i.e. one atmosphere).

B. DISCLOSED MONOMERS AND MONOMER PRECURSORS

In various aspects, the present disclosure pertains to monomer compounds that can be used in the disclosed synthetic methods, e.g., preparation of the disclosed polymers. In a further aspect, the present disclosure pertains to compounds that can be used in the preparation of the disclosed monomers.