Synthesis of Ladder Polymers: Developments, Challenges, and Opportunities.

Ladder polymers are unique in that their backbones consist of fused rings with adjacent rings having two or more atoms in common. The restriction of bond rotations in rigid ladder polymers greatly limits their conformational freedom, leading to many intriguing and unique properties. As a non-traditional type of polymers, rigid ladder polymers are of great fundamental interest and technical importance as advanced materials for applications such as membrane gas separation and organic electronics. Ladder polymers can be divided into non-conjugated (with kinked conformations) and conjugated (with planar conformations) structures. Their synthesis can be broadly classified into two general strategies: direct ladder polymerization, and zipping of a linear precursor polymer. This Concept article outlines the historical development of ladder polymers and the chemical strategies used for their synthesis; highlights the challenges associated with their synthesis and characterization, and presents opportunities and outlooks for this unique and intriguing type of polymers.

Conformational preferences of N,N-dimethylsuccinamate as a function of alkali and alkaline earth metal salts: experimental studies in DMSO and water as determined by 1H NMR spectroscopy.

The fraction of gauche conformers of N,N-dimethylsuccinamic acid (1) and its Li(+), Na(+), K(+), Mg(2+), Ca(2+), and N(Bu)4(+) salts were estimated in DMSO and D2O solution by comparing the experimental vicinal proton-proton couplings determined by (1)H NMR spectroscopy with those calculated using the Haasnoot, de Leeuw, and Altona (HLA) equation. In DMSO, the gauche preferences were found to increase with decreasing Ahrens ionic radius of the metal counterion. The same trend was not seen in D2O, where the gauche fraction for all of the metallic salts were estimated to be approximately statistical or less. This highlights the importance of metal chelation on the conformation of organic molecules in polar aprotic media, which has implications for protein folding.

Hydrocarbon ladder polymers with ultrahigh permselectivity for membrane gas separations.

Membranes have the potential to substantially reduce energy consumption of industrial chemical separations, but their implementation has been limited owing to a performance upper bound-the trade-off between permeability and selectivity. Although recent developments of highly permeable polymer membranes have advanced the upper bounds for various gas pairs, these polymers typically exhibit limited selectivity. We report a class of hydrocarbon ladder polymers that can achieve both high selectivity and high permeability in membrane separations for many industrially relevant gas mixtures. Additionally, their corresponding films exhibit desirable mechanical and thermal properties. Tuning of the ladder polymer backbone configuration was found to have a profound effect on separation performance and aging behavior.

Facile Synthesis and Study of Microporous Catalytic Arene-Norbornene Annulation-Tröger's Base Ladder Polymers for Membrane Air Separation.

We report the facile synthesis and study of two soluble microporous ladder polymers, CANAL-TBs, by combining catalytic arene-norbornene annulation (CANAL) and Tröger's base (TB) formation. The polymers were synthesized in two steps from commercially available chemicals in high yields. CANAL-TBs easily formed mechanically robust films, were thermally stable up to 440 °C, and exhibited very high Brunauer-Teller-Emmett surface areas of 900-1000 m2 g-1. The gas separation performance of the CANAL-TBs for the O2/N2 pair is located between the 2008 and 2015 permeability/selectivity upper bounds. After 300 days of aging, CANAL-TBs still exhibited O2 permeability of 200-500 barrer with O2/N2 selectivity of about 5. The polymer with more methyl substituents exhibited higher permeability and slightly larger intersegmental spacing as revealed by WAXS, presumably due to more frustrated chain packing. The facile synthesis, excellent mechanical properties, and promising air separation performance of the CANAL-TB polymers make them attractive membrane materials for various air separation applications, such as aircraft on-board nitrogen generation and oxygen enrichment for combustion.

Glucuronide-Linked Antibody-Tubulysin Conjugates Display Activity in MDR+ and Heterogeneous Tumor Models.

Although antibody-drug conjugates (ADCs) find increasing applications in cancer treatment, de novo or treatment-emergent resistance mechanisms may impair clinical benefit. Two resistance mechanisms that emerge under prolonged exposure include upregulation of transporter proteins that confer multidrug resistance (MDR+) and loss of cognate antigen expression. New technologies that circumvent these resistance mechanisms may serve to extend the utility of next-generation ADCs. Recently, we developed the quaternary ammonium linker system to expand the scope of conjugatable payloads to include tertiary amines and applied the linker to tubulysins, a highly potent class of tubulin binders that maintain activity in MDR+ cell lines. In this work, tubulysin M, which contains an unstable acetate susceptible to enzymatic hydrolysis, and two stabilized tubulysin analogues were prepared as quaternary ammonium-linked glucuronide-linkers and assessed as ADC payloads in preclinical models. The conjugates were potent across a panel of cancer cell lines and active in tumor xenografts, including those displaying the MDR+ phenotype. The ADCs also demonstrated potent bystander activity in a coculture model comprised of a mixture of antigen-positive and -negative cell lines, and in an antigen-heterogeneous tumor model. Thus, the glucuronide-tubulysin drug-linkers represent a promising ADC payload class, combining conjugate potency in the presence of the MDR+ phenotype and robust activity in models of tumor heterogeneity in a structure-dependent manner. Mol Cancer Ther; 17(8); 1752-60. ©2018 AACR.

Functionalized Rigid Ladder Polymers from Catalytic Arene-Norbornene Annulation Polymerization.

Rigid ladder polymers represent a unique polymer architecture but have limited synthetic accessibility and structural diversity. Using catalytic arene-norbornene annulation (CANAL) polymerization, we synthesized ladder polymers consisting of rigid and kinked norbornyl benzocyclobutene backbones and bearing various functional groups, such as alcohol, amine, ester, carbamate, amide, benzyl bromide, azide, and heterocycles. The incorporation of functional groups was achieved by either copolymerization of functionalized ladder-type dinorbornenes or postpolymerization functionalization. Functionalization of ladder polymers allows modification of their solubility, compatibility, and other properties, expanding their utilities. These ladder polymers remain microporous and highly glassy, which are desirable for separation and high-temperature applications.

High surface area and Z' in a thermally stable 8-fold polycatenated hydrogen-bonded framework.

1,3,5-Tris(4-carboxyphenyl)benzene assembles into an intricate 8-fold polycatenated assembly of (6,3) hexagonal nets formed through hydrogen bonds and π-stacking. One polymorph features 56 independent molecules in the asymmetric unit, the largest Z' reported to date. The framework is permanently porous, with a BET surface area of 1095 m(2) g(-1) and readily adsorbs N2, H2 and CO2.