Matthew R. Golder

Selective Synthesis of Strained [7]Cycloparaphenylene: An Orange-Emitting Fluorophore

[n]Cycloparaphenylenes, which are short fragments of carbon nanotubes, have unique size-dependent optical properties. In this communication, we describe the first synthesis of [7]cycloparaphenylene ([7]CPP), the smallest cycloparaphenylene prepared to date. In order to access this structure, we have developed a synthetic route that capitalizes on successive orthogonal Suzuki-Miyaura coupling reactions. [7]CPP has 83 kcal/mol of strain energy and an orange emission at 592 nm.

Synthesis, Characterization, and Computational Studies of Cycloparaphenylene Dimers

Two novel arene-bridged cycloparaphenylene dimers (1 and 2) were prepared using a functionalized precursor, bromo-substituted macrocycle 7. The preferred conformations of these dimeric structures were evaluated computationally in the solid state, as well as in the gas and solution phases. In the solid state, the trans configuration of 1 is preferred by 34 kcal/mol due to the denser crystal packing structure that is achieved. In contrast, in the gas phase and in solution, the cis conformation is favored by 7 kcal/mol (dimer 1) and 10 kcal/mol (dimer 2), with a cis to trans activation barrier of 20 kcal/mol. The stabilization seen in the cis conformations is attributed to the increased van der Waals interactions between the two cycloparaphenylene rings. These calculations indicate that the cis conformation is accessible in solution, which is promising for future efforts toward the synthesis of short carbon nanotubes (CNTs) via cycloparaphenylene monomers. In addition, the optoelectronic properties of these dimeric cycloparaphenylenes were characterized both experimentally and computationally for the first time.

Self-Trapping of Excitons, Violation of Condon Approximation, and Efficient Fluorescence in Conjugated Cycloparaphenylenes

Cycloparaphenylenes, the simplest structural unit of armchair carbon nanotubes, have unique optoelectronic properties counterintuitive in the class of conjugated organic materials. Our time-dependent density functional theory study and excited state dynamics simulations of cycloparaphenylene chromophores provide a simple and conceptually appealing physical picture explaining experimentally observed trends in optical properties in this family of molecules. Fully delocalized degenerate second and third excitonic states define linear absorption spectra. Self-trapping of the lowest excitonic state due to electron-phonon coupling leads to the formation of spatially localized excitation in large cycloparaphenylenes within 100 fs. This invalidates the commonly used Condon approximation and breaks optical selection rules, making these materials superior fluorophores. This process does not occur in the small molecules, which remain inefficient emitters. A complex interplay of symmetry, π-conjugation, conformational distortion and bending strain controls all photophysics of cycloparaphenylenes.

Photophysical and theoretical investigations of the [8]cycloparaphenylene radical cation and its charge-resonance dimer

Treatment of [8]cycloparaphenylene (CPP) with the oxidant triethyloxonium hexachloroantimonate afforded an isolable radical cation of the parent carbon nanohoop. The photophysical properties of [8]CPP˙+SbCl6− were investigated, showing the presence of two absorptions at 535 nm and 1115 nm. Time-dependent density functional theory (DFT) calculations were used to examine these optical absorptions, revealing a delocalized, quinoidal carbon nanohoop. Upon mixing with neutral [8]cycloparaphenylene, the formation of an unusually strong charge-resonance complex ([8]CPP2)˙+ was observed. Spectroscopic and computational studies were indicative of extensive intermolecular charge delocalization between the two carbon nanohoops as well.

Iterative Reductive Aromatization/Ring-Closing Metathesis Strategy toward the Synthesis of Strained Aromatic Belts

The construction of all sp(2)-hybridized molecular belts has been an ongoing challenge in the chemistry community for decades. Despite numerous attempts, these double-stranded macrocycles remain outstanding synthetic challenges. Prior approaches have relied on late-state oxidations and/or acid-catalyzed processes that have been incapable of accessing the envisaged targets. Herein, we describe the development of an iterative reductive aromatization/ring-closing metathesis approach. Successful syntheses of nanohoop targets containing benzo[k]tetraphene and dibenzo[c,m]pentaphene moieties not only provide proof of principle that aromatic belts can be derived by this new strategy but also represent some of the largest aromatic belt fragments reported to date.

Iterative Exponential Growth Synthesis and Assembly of Uniform Diblock Copolymers

Studies on the phase segregation of unimolecular block copolymers (BCPs) are limited by a lack of reliable, versatile methods for the synthesis of such polymers on the preparative scale. Herein, we describe an advancement of Iterative Exponential Growth (IEG) wherein chiral allyl-based IEG oligomers are subjected to thiol-ene reactions and converted into unimolecular BCPs. With this strategy we have synthesized uniform BCPs with molar masses up to 12.1 kDa on ∼1 g scale. BCPs composed of decane-based side chains and either triethyleneglycol- or thioglycerol-based side chains phase-segregate into hexagonal cylinder morphologies. The assembly is not driven by side-chain crystallization, but is instead the result of amorphous BCP assembly.

Stereochemical Sequence Dictates Unimolecular Diblock Copolymer Assembly

Deciphering the significance of length, sequence, and stereochemistry in block copolymer self-assembly remains an ongoing challenge. A dearth of methods to access uniform block co-oligomers/polymers with precise stereochemical sequences has precluded such studies. Here, we develop iterative exponential growth methods for the synthesis of a small library of unimolecular stereoisomeric diblock 32-mers. X-ray scattering reveals that stereochemistry modulates the phase behavior of these polymers, which we rationalize based on simulations carried out on a theoretical model system. This work demonstrates that stereochemical sequence can play a crucial role in unimolecular polymer self-assembly.

Reduction of liver fibrosis by rationally designed macromolecular telmisartan prodrugs

At present there are no drugs for the treatment of chronic liver fibrosis that have been approved by the Food and Drug Administration of the United States. Telmisartan, a small-molecule antihypertensive drug, displays antifibrotic activity, but its clinical use is limited because it causes systemic hypotension. Here, we report the scalable and convergent synthesis of macromolecular telmisartan prodrugs optimized for preferential release in diseased liver tissue. We have optimized the release of active telmisartan in fibrotic liver to be depot-like (that is, a constant therapeutic concentration) through the molecular design of telmisartan brush-arm star polymers, and show that these lead to improved efficacy and to the avoidance of dose-limiting hypotension in both metabolically and chemically induced mouse models of hepatic fibrosis, as determined by histopathology, enzyme levels in the liver, intact-tissue protein markers, hepatocyte necrosis protection and gene-expression analyses. In rats and dogs, the prodrugs are retained long term in liver tissue, and have a well-tolerated safety profile. Our findings support the further development of telmisartan prodrugs that enable infrequent dosing in the treatment of liver fibrosis.Macromolecular telmisartan prodrugs optimized for preferential release in fibrotic liver tissue reduce liver fibrosis in mouse models, and are retained and well tolerated in the liver tissue of rats and dogs.

Stereochemical implications toward the total synthesis of aromatic belts

Abstract The synthesis of carbon nanotube (CNT) fragments has long captivated organic chemists, despite the simplistic, symmetric nature of the requisite achiral targets. Such molecules hold the potential to allow for the synthesis of homogeneous CNTs, rendering their properties more suitable for advanced applications in electronics and sensing. The [n]cycloparaphenylene family, comprised of molecules with para-linked phenyl rings in a contiguous macrocycles, represents a major landmark towards achieving absolute control of CNT architecture from the bottom-up. Attempts towards accessing the [n]cyclacene and [n]cyclophenacene families, both of which are comprised of double-stranded macrocyclic belts, have only recently been successful, however. These targets have been plagued by unstable, strained intermediates and stereochemical pitfalls that have largely thwarted accessing these fascinating structures. Herein, we disclose our synthetic strategy toward overcoming several stereochemical challenges en route to [n]cyclophenacenes via highly substituted [n]cycloparaphenylene precursors.