From the novel DNA delivery system for the treatment of asthma to the straightforward means of introducing interactive, three-dimensional figures into PDFs, UConn researchers made significant breakthroughs in the field of chemistry in 2021.
Xia, Y.; Song, Z.; Tan, Z.; Xue, T.; Wei, S.; Zhu, L.; Yang, Y.; Fu, H.; Jiang, Y.; Lin, Y.; Lu, Y.; Ferguson, A. L., Cheng, L. “Accelerated polymerization of N-carboxyanhydrides catalyzed by crown ether,” Nat. Commun., 2021, 12, 732. (https://doi.org/10.1038/s41467-020-20724-w).
The group of Prof. Yao Lin, with a number of co-workers, demonstrated advances in the accelerated polymerization of N-carboxyanhydrides (NCAs). The use of crown ether (CE) to catalyze the polymerization of NCA was reported, with 18-crown-6 enabling the fastest polymerization kinetics. The fast polymerization kinetics outpaced common side reactions, enabling the preparation of well-defined polypeptides using an α-helical macroinitiator. This work enriched the toolbox to prepare well-defined polypeptide materials and guides the design of catalysts for NCA polymerization.
Gavitt, T. D.; Hartmann, A. K.; Mara, A. B.; Szczepanek, S. M.; Rouge, J. L., "A GATA3-Targeting Nucleic Acid Nanocapsule for the Treatment of Allergic Lung Inflammation in a Mouse Model of Asthma” ACS Nano, 2021, 15, 11192. (https://doi.org/10.1021/acsnano.0c07781).
In collaboration with the research group of Prof. Steven Szczepanek (Department of Pathobiology), the group of Prof. Jessica Rouge reported on the use of their novel DNA delivery system for the treatment of asthma. Their nucleic acid (DNA/RNA) delivery system is referred to as a nucleic acid nanocapsule (NAN) and was designed to silence the expression of a protein that initiates inflammation in the lungs. By chemically designing a particle that could be degraded by enzymes in the lungs that are released during periods of inflammation, they showed that their formulation could suppress the expression of the target gene, GATA-3, both in cell culture and in a mouse house dust mite model of asthma. This resulted in effectively lowering the level of eosinophils in the lungs - a hallmark of asthma.
Chatterjee, S.; Moon, S.; Rowlands, A.; Chin, F.; Seeberger, P. H.; Merbouh, N.; Gilmore, K. "Click, Zoom, Explore: Interactive 3D (i-3D) Figures in Standard Teaching Materials (PDFs)” J. Chem. Ed. 2021, 98, 3470 (https://doi.org/10.1021/acs.jchemed.1c00296).
In collaboration with a team lead by former Husky Prof. Nabyl Merbouh (Simon Fraser University) and researchers from the Max-Planck Institute of Colloids and Interfaces in Potsdam, Germany, the group of Prof. Kerry Gilmore reported a straightforward means of introducing interactive, three-dimensional figures into PDFs. These figures can be utilized for a wide range of applications, including complex chemical and biological structures such as transition states and proteins, and can have a significant impact for students when provided as teaching aids.
Yan, J.; Wilson, R. W.; Buck, J. T.; Grills, D. C.; Reinheimer, E. W.; Mani, T. "IR linewidth and intensity amplifications of nitrile vibrations report nuclear-electronic couplings and associated structural heterogeneity in radical anions” Chem. Sci. 2021, 12, 12107 (https://doi.org/10.1039/D1SC03455C).
The group of Prof. Tomoyasu Mani reported that intensities of local nitrile (C≡N) infrared (IR) bands in CN-substituted oligophenylenes reveal strong coupling to electronic structure, rising with excess charge and delocalization by >50 x compared to the neutral monomer. Linewidths also show strong effects, probing electronic-nuclear structure changes in these molecular wires. The study demonstrates that intensities and linewidths are also powerful probes of excess charges in molecules relevant to solar energy conversion and quantum information science.
Saavedra-Avila, N. A.; Keshipeddy, S.; Guberman-Pfeffer, M. J.; Pérez-Gallegos, A.; Saini, N. K.; Schäfer, C.; Leandro J. Carreño, L. J.; Gascón, J. A.; Porcelli, S. A.; Howell, A. R. “Amide-Linked C4”-Saccharide Modification of KRN7000 Provides Potent Stimulation of Human Invariant NKT Cells and Anti-Tumor Immunity in a Humanized Mouse Model,” ACS Chem. Biol. 2020, 15, 3176 (https://dx.doi.org/10.1021/acschembio.0c00707).
The research groups of Profs. Jose Gascón, Amy Howell, and Steven A. Porcelli (Albert Einstein College of Medicine) reported the synthesis and evaluation of sugar modified variants of the prototypical iNKT stimulatory a-galactosyl ceramide, KRN7000. These variants had weak iNKT cell stimulating activity in mouse models, but substantially greater activity for human iNKT cells. The most active of the C4’’‑amides showed strong anti-tumor effects in a partially humanized mouse model for iNKT cell responses. In silico analysis suggested structure-function relationships. The studies highlighted the critical need for more accurate animal models to assess glycolipids for their immunotherapeutic potential in humans.
An, J.; Intano, J.; Richard, A.; Kim, T.; Gascón, J. A.; Howell, A. R. "Easily Accessible Non-Aromatic Heterocycles with Handles: 4-Bromo-2,3-Dihydrofurans from 1,2-Dibromohomoallylic Alcohols," Chem. Sci. 2021, 12, 10347 (https://doi.org/10.1039/D1SC01013A).
The research groups of Profs. Jose Gascón and Amy Howell reported the first general preparation of 4-bromo-2,3-dihydrofurans. These non-aromatic heterocycles containing a useful coupling handle are accessed via Cu-catalyzed intramolecular cyclization of 1,2-dibromohomoallylic alcohols, which are themselves available in just two steps from aromatic and aliphatic aldehydes and ketones. Molecular dynamics simulations provided a rationale for the selectivities observed.
Chaudhri, N.; Guberman-Pfeffer, M.J.; Li, R.; Zeller, M.; Brückner, C. “ß-Trioxopyrrocorphins: Pyrrocorphins of Graded Aromaticity” Chem. Sci. 2021, 12, 12292 (https://doi.org/10.1039/D1SC03403K).
Aromaticity is one of the key concepts in chemistry. Porphyrins are a prime example of 18 π-aromatic systems, containing also two so-called cross-conjugated double bonds. It was previously believed that removal of more than these two double bonds from conjugation results in a non-aromatic macrocycle. Using experimental data and theory – provided by alum Dr. Matthew Guberman-Pfeffer, this paper by the group of Prof. Christian Brückner demonstrated that this is not necessarily the case.
E Moharreri, E.; Jafari, T.; Rathnayake, D.; Khanna, H.; Kuo, C.H.; Suib, S.L. “Role of catalytic nitrile decomposition in tricopper complex mediated direct partial oxidation of methane to methanol” Sci. Rep. 2021, 11, 19175 (https://doi.org/10.1038/s41598-021-98721-2).
The group of Prof. Steven Suib, together with colleagues from Exxon Mobile, provided insight into the unique homogeneous system that converts methane to methanol using O2 as terminal oxidant in a medium of acetonitrile. This paper shows that the reaction might be mediated by a catalytic Radziszewski oxidation between acetonitrile and H2O2. Additionally they discovered that in the absence of methane, peroxide mediated acetonitrile decomposition also makes methanol via a background reaction which was hitherto unknown.
