Tag: Michael Haley

Alkaline Synthesis of Amidines – A New Approach to Preparing Medicinally Relevant Small Molecules

Presenter : Muhammad Khalifa

Mentor : Michael Haley

Major : Biochemistry

Poster 16

Myotonic dystrophy (DM) is the most common adult form of muscular dystrophy. Recently, the small molecule pentamidine has been shown to relieve symptoms of DM in cell models; however, pentamidine is an inadequate drug for DM because of toxicity and bioavailability problems. Analogs of pentamidine, generically termed amidines, have proven to be significant candidates in the search for an effective cure for DM. It is therefore important to have access to the widest possible range of amidine structures for study against symptoms of DM. Existing methods of synthesizing amidines have largely depended upon reactions with acidic con- ditions; features of these reactions have limited the accessible range of amidines, especially substituted amidines. Here we outline a new method of preparing substituted amidines using alkaline conditions that features shorter reaction times, better yields, and better compatibility with many of our compounds of interest. Through synthesis and NMR characterization, we explore the range of usable starting materials, test the method’s selectivity in the presence of competing reactions, and demonstrate its application to the synthesis of several novel compounds. This method makes possible a host of new substituted amidine compounds that could prove useful in the search for a cure for DM, and provides a new, potentially more efficient, synthetic path to unsubstituted amidines for the same purpose.

Alkaline Synthesis of Amidines—Exploring a New Approach to Accessing a Pharmaceutically Relevant Functional Group

Presenter: Muhammad Khalifa

Mentor: Michael Haley

Oral Presentation

Major: Biochemistry

Aryl amidines have been used against a variety of diseases, most notably pneumocystis pneumonia. They continue to be relevant in the search for cures against malaria, Alzheimer’s disease, and myotonic dystrophy type
1 (DM1). Current methods of amidine synthesis feature harsh, acidic reaction conditions that limit possibilities for functionalization of the amidine group, a process of particular interest in developing small molecule therapeutics
for DM1. Preparation of amidines via basic conditions has been described, but not well studied. Here we outline a method of preparing N-substituted aryl amidines under alkaline conditions and examine the accessibility of series
of amidines to delineate important properties of this synthetic approach. Our results indicate that increasing the nucleophilicity of the amine and/or increasing the electrophilicity of the nitrile afford higher yields of the desired amidine. Results also show that alkaline synthesis is sufficiently chemoselective to form amidines in the presence of competing, nucleophilic aromatic substitution sites on the nitrile. Featuring reaction times at least 50% shorter, up to 40% greater yields, and better compatibility with a broad range of starting materials, our method of alkaline amidine synthesis makes accessible a host of new N-substituted amidines for study in a variety of diseases previously described.

Asymmetrical Heteroatom Substitution in the Indenofluorene Framework

Presenter: Nathaniel O’Neal

Mentors: Michael Haley and Jonathan Marshall, Chemistry

Poster: 49

Major: Biochemistry 

Semiconductors are a key component in electronics because they allow for the control of electron flow throughout a device. Research has shown that organic molecules can act as semiconductors and could prove superior to current semiconductors in use. To further this field of study the Haley lab has developed and experimented on the indenofluorene, an n-type organic semiconductor. However, most of the work done on the framework has been on symmetrical heteroatom substitutions. This has left me with the task of using synthetic chemistry techniques in order to produce asymmetrical heteroatom substituted indenofluorene molecules known as benzo-indaceno-thiophenes. Theoretically, this asymmetry will allow for superior stacking of the molecules in a crystal structure and allow for more efficient electron transfer than its symmetrical predecessors. To date, the substitutions have not made a significant of enough change to the overall motif of the structure to produce a notable difference but the knowledge garnered from such experimentation is valuable to the field as a whole.

Synthesis of Diindenoanthracene Derivatives for use in Organic Field-Effect Transistors

Presenter: Victoria Stanfill

Faculty Mentor: Michael Haley, Geri Richmond

Presentation Type: Poster 39

Primary Research Area: Science

Major: Chemistry

Funding Source: Presidential Undergraduate Research Scholars Program, $5000

Organic field-effect transistors (OFETs) are a type of organic electronic device that determine how and where charge flows throughout a system. They are important to the electronic industry because they are longer lasting and cheaper to synthesize than traditional silicon field-effect transistors. OFETs are ranked on their charge mobility, the speed and quality of the charge transfer. Diindenoanthracenes are a type of organic small molecule with potential to be used in OFETs because of their biradical character, giving them the ability to transport charge. Our research focuses on synthesizing a variety of diindenoanthracene derivatives so we have a large range of molecules with different electronic properties to test in devices. The ultimate goal is to increase the charge mobility of these molecules so that these electronic devices are comparable to traditional inorganic electronics. So far we have created one new diindenoanthracene which has yet to be tested in devices, but we are working towards creating a more generalized synthesis method to make it possible to add a variety of substituents to the general diindenoanthracene scaffold.

Synthesis of 7,14-Diarylfluoreno[3,2-b]fluorenes

Presenter(s): Tristan Mistkawi − Biochemistry

Faculty Mentor(s): Josh Barker, Michael Haley

Poster 74

Research Area: Organic Chemistry (Natural/Physical Science)

Funding: UROP Mini-grant

The Haley group is interested in a class of organic molecules, known as the indenofluorene (IF) scaffold, for potential use as organic semiconductors (OSCs) in electronic devices. IFs show great promise as OSCs because of their ability to easily and reversibly accept electrons. Similarly to the well-known class of acene OSCs, we are interested in studying the effect of extending IF scaffold -conjugation to discover trends in electronic properties. While other researchers in the literature have studied compounds with similar properties, no one has performed a rational, systematic study. This work requires exploring the synthesis of several 7,14-diarylfluoreno[3,2-b]fluorenes (FFs) to compare to structurally related molecules in the IF scaffold. Along with affecting the optoelectronic properties of FFs, substituting different aryl groups at specific positions on the molecule is important for crystal engineering, which will help improve our understanding of this novel scaffold. Many derivatives have not been explored yet, and studying solid-state packing interactions may improve device performance and influence our ability to implement these compounds as organic semiconductors.

The Effect of Different Substituents on the Optoelectronic Properties of Diindenoanthracene

Presenter(s): Brian Chastain − General Science

Faculty Mentor(s): Michael Haley, Justin Dressler

Poster 21

Research Area: Natural/Physical Science (Synthetic Organic Chemistry)

Funding: University of Oregon Summit Scholarship, OSEA Guy Davis Scholarship, General Chemistry Achievement Award

The properties of molecules containing unpaired electrons have been of interest to chemists ever since the first known diradical species was synthesized in 1907. More recently in 2016, the diradical molecule diindenoanthracene (DIAn) was synthesized by the Haley group. This species is of interest because of its marked stability for a molecule exhibiting diradical character. Additionally, the ability to form a dione intermediate that can react with a wide range of nucleophiles enables us to conduct a similar study to that performed by Chase et. al. on the parent indeno[1,2-b]fluorene. In this study it was discovered that the inclusion of different groups could have strong effects on the optoelectronic properties of the molecule. Here, we explore the effect of the addition of electron-withdrawing and donating groups to DIAn, specifically examining the change in the magnitude of the HOMO-LUMO energy gap, and thus the wavelength of maximum absorption in the electronic absorption spectrum. To test the effect of the groups on the properties of DIAn, nucleophilic addition reactions have been utilized to substitute the apical carbon with electron-withdrawing and donating groups. This will allow us to determine
if there are similar trends in the optoelectronic properties between the parent indeno[1,2-b]fluorene and the anthracene extended DIAn. This study will provide insight that will allow us to further refine our design principles for the preparation of organic semiconducting molecules.

Modulating Diradical Character in Indenoindenodibenzothiopene and Benzofluorenofluorene Structures For Ultimate Application Within Organic Electronics

Presenter(s): Eric Strand

Faculty Mentor(s): Michael Haley & Joshua Barker

Poster 51

Session: Sciences

The Haley Lab is interested in the synthesis and characterization of organic hydrocarbon scaffolds which can be used as semiconductors. The family of indenofluorene hydrocarbons exhibit unique electronic properties such as antiaromaticity and diradical character, which contribute to their allure for scientists. Our lab has developed highly modular synthetic routes toward many analogues of this parent scaffold, which can be further optimized through subtle synthetic tuning. Our ultimate goal is to create a library of analogues with tuned electronic characteristics such that we may identify the most promising candidates for device implementation. Fusing a variety of aryl moieties onto the parent scaffold allows for this by decreasing the HOMO-LUMO energy gap and subsequently improvement in electron mobility and conductivity. Initially focused on proving the diradical character in an analogue of indenoindenodibenzothiopene, our current project has successfully shown this by reacting the molecule through a known radical degradation pathway.

Our studies into indenofluorenes have shown promise in regard to the ability of these molecules to serve as potential replacements for current inorganic counterparts within devices. Continuous fundamental studies into the electronic abilities of these molecules will help to elucidate the ideal characteristics of organic semiconductors, which is imperative for the feasible implementation of these molecules into devices. This project is now focused on the optimization of previous synthetic routes such that further studies into these highly interesting molecules can be carried out.