Davita L. Watkins

Synergistic effects of halogen bond and π–π interactions in thiophene-based building blocks

Although recognized as a significant force in crystal engineering, halogen bonding (XB) has been scarcely investigated in “bottom-up” approaches towards organic electronics. We report, herein, the use of a thiophene-based building block, pyridyl-thiophene (Pyr-T), to achieve an assembly driven by XB and π–π stacking interactions with iodopentafluorobenzene (IPFB). Spectroscopic and thermal analysis of the co-crystal provide indirect evidence of the assembly. The combined effects of XB and π–π stacking are confirmed experimentally via X-ray crystallography. Density functional theory (DFT) computations support experimental observations. The results of the study speak to the use of halogen bond driven self-assembly in organic electronic device application.

Molecular Engineering of Near Infrared Absorbing Thienopyrazine Double Donor Double Acceptor Organic Dyes for Dye-Sensitized Solar Cells

The thienopyrazine (TPz) building block allows for NIR photon absorption in dye-sensitized solar cells (DSCs) when used as a π-bridge. We synthesized and characterized 7 organic sensitizers employing thienopyrazine (TPz) as a π-bridge in a double donor, double acceptor organic dye design. Donor groups are varied based on electron donating strength and sterics at the donor-π bridge bond with the acceptor groups varied as either carboxylic acids or benzoic acids on the π-bridge. This dye design was found to be remarkably tunable with solution absorption onsets ranging from 750 to near 1000 nm. Interestingly, the solution absorption measurements do not accurately approximate the dye absorption on TiO2 films with up to a 250 nm blue-shift of the dye absorption onset on TiO2. This shift in absorption and the effect on electron transfer properties is investigated via computational analysis, time-correlated single photon counting studies, and transient absorption spectroscopy. Structure-performance relationships were analyzed for the dyes in DSC devices with the highest performance observed at 17.6 mA/cm2 of photocurrent and 7.5% PCE for a cosensitized device with a panchromatic IPCE onset of 800 nm.

Quantifying the effects of halogen bonding by haloaromatic donors on the acceptor pyrimidine

The effects of intermolecular interactions by a series of haloaromatic halogen bond donors on the normal modes and chemical shifts of the acceptor pyrimidine are investigated by Raman and NMR spectroscopies and electronic structure computations. Halogen-bond interactions with pyrimidines nitrogen atoms shift normal modes to higher energy and upfield shift 1 H and 13 C NMR peaks in adjacent nuclei. This perturbation of vibrational normal modes is reminiscent of the effects of hydrogen bonded networks of water, methanol, or silver on pyrimidine. The unexpected observation of vibrational red shifts and downfield 13 C NMR shifts in some complexes suggests that other intermolecular forces such as π interactions are competing with halogen bonding. Natural bond orbital analyses indicate a wide range of charge transfer is possible from pyrimidine to different haloaromatic donors and computed halogen bond binding energies can be larger than a typical hydrogen bond. These results emphasize the importance in strategic selection of substituents and electron withdrawing groups in developing supramolecular structures based on halogen bonding.

Design of Potent Panobinostat Histone Deacetylase Inhibitor Derivatives: Molecular Considerations for Enhanced Isozyme Selectivity between HDAC2 and HDAC8

Histone Deacetylases (HDACs) are an important family of 18 isozymes, which are being pursued as drug targets for many types of disorders. HDAC2 and HDAC8 are two of the isozymes, which have been identified as drug targets for the design of anti‐cancer, neurodegenerative, immunological, and anti‐parasitic agents. Design of potent HDAC2 and HDAC8 inhibitors will be useful for the therapeutic advances in many disorders. This work was undertaken to develop potent HDAC2 and HDAC8 inhibitors. A docking study was performed comparing panobinostat derivatives in both HDAC2 and HDAC8. Six of our derivatives showed stronger binding to HDAC2 than panobinostat, and two of our derivatives showed stronger binding to HDAC8 than panobinostat. We evaluated the molecular features, which improved potency of our inhibitors over panobinostat and also identified another molecular consideration, which could be used to enhance histone deacetylase inhibitor (HDACi) selectivity towards either the HDAC2 or HDAC8 isozymes. The results of this work can be used to assist future design of more potent and selective HDACi for HDAC2 and HDAC8.

Tuning the structural and spectroscopic properties of donor–acceptor–donor oligomers via mutual X-bonding, H-bonding, and π–π interactions

Presented are design strategies towards hierarchically assembling a C2-symmetric π-conjugated oligomer (DAD-XB-Boc) based on a donor–acceptor–donor motif through hydrogen bonding (HB), halogen bonding (XB), and π-stacking interactions. Upon co-crystallization with tetrafluoro-1,4-diiodobenzene (TFDIB), single crystal X-ray analysis reveals highly directional XB induced 2D assemblies which further organize via π–π interactions. Crystal photoluminescence (PL) analysis indicates that the co-crystal exhibits a red shift in its PL spectrum with enhanced intensity compared to the mono-crystal. Pyrolytic cleavage and removal of the t-butyloxycarbonyl (Boc) groups of DAD-XB-Boc exposes complementary hydrogen bonding sites; the H-bonding capability of DAD-XB-NH is evident from thermal gravimetric analysis (TGA) and infrared (IR) spectroscopy. Overall, the data show that both halogen and hydrogen bonding can be used together with π-stacking interactions to enhance the solid-state properties of DAD oligomers essential for optoelectronic device applications. Ongoing work seeks to use such supramolecular approaches to control the nanoscale to microscale arrangement of molecules in thin films and increase device efficiency (i.e., charge mobility).

Benzotriazole-Based Strategies Toward Peptidomimetics, Conjugates, and Other Peptide Derivatives

Benzotriazole-mediated routes to peptidomimetics and peptide conjugates have been discussed in detail. The Katritzky group developed a benzotriazole methodology toward the activation of carbonyl groups of amino acids and modified analogs, which allowed the synthesis of cyclic peptides, azapeptides, azidopeptides, aminoxypeptides, oxyazapeptides, depsipeptides, and isopeptides. High-yielding reactions of N-, O-, S-, and C-acylated nucleophiles with activated aminoacyl or peptidoyl benzotriazole derivatives have also been reported. Benzotriazole methodology enabled the efficient incorporation of bioactive moieties into peptides, peptidomimetics, amino acids, and other carbonyl-containing compounds. Predominant number of reported products retained chiral purity. Some of the products displayed promising biological activities such as anticancer and antibacterial activity along with the improved stability under physiological conditions.