Reports: UR454862-UR4: Employing gamma-Cyclodextrin to Mediate Photo-Heterodimerization of Alkenes in the Solid-State

Mahesh Pattabiraman, University of Nebraska Kearney

PROGRESS REPORT, YEAR 2 (2016 to 2017)

Summary: The second year of research supported by ACS PRF resulted in the exploration of two new photosubstrate systems: photodimerization of naphthyl-acrylic acids, and heterodmerization of halogen-substituted cinnamic acids. In the former case, we have established that the reactant undergoes efficient photodimerization if included within the γ-cyclodextrin (γ-CD). The reaction mediated by the cavitand affords syn H-H dimer selectively, even in case of sterically-demanding alkyl group-substituted ester derivatives. In case of heterodimerization between halogen-substituted cinnamic acids, current data suggest that the homo dimers and heterodimers are formed in approximately equal quantities indicating lack of distinction between the homo-halogen and cross-halogen interactions.

The above findings resulted in two major talks in national and international meetings, three talks by undergraduate students, and five poster presentations by undergraduate students. Two papers are currently under preparation for submission in peer-reviewed journals. Data generated from this project was used to submit several external grants, of which an NIH program grant. One external grant ($100,000 2017 - 2019) was awarded. In addition, two invited review articles were submitted – the PRF grant was acknowledged in both.

Detailed progress report: Cavitand-mediated photochemistry of naphthyl acrylic acids (NAA) was performed to understand the nature of weak interactions involving dinuclear aromatic systems. The stacking of mono-nuclear alkene reactants (the cinnamic acids) within γ-CD that were studied earlier suggested strong directing effect of the π-π interaction, which was responsible for the exclusive formation of syn H-H dimer. Isomeric NAAs encapsulated within γ-CD resulted in exclusive formation of the syn H-H dimer as well, which would be expected from the previous results. Alkyl esters of NAAs also yielded exclusively syn H-H dimers; whereas, the isopropyl ester of mononuclear equivalents yielded selectively the anti H-T dimers. This provided a qualitative measure of the attractive influence of the naphthyl moieties, which could overcome the steric repulsion between isopropyl groups. Currently efforts are underway to obtain crystal structure of the dimers for publication. Computational studies performed at HF-631G* level provided insight into the strength of the pi-pi interaction, which corroborated our experimental findings. In addition, binding studies using NMR, UV-Vis, and fluorimetric titrations confirm the formation of predominantly 1:2 complex.

Halogen-halogen interaction is one of the under-studied supramolecular interactions. The interaction between two different halogens (non-identical halogens) is even less studied. We performed the photodimerization of halogenated phenyl acrylic acids (cinnamic acids, CA) within γ-cyclodextrin to compare the strengths of interaction between homo-halogen and hetero-halogen interactions. The reaction was performed with two different alkenes (bromo-CA and chloro-CA) in presence of γ-CD. Currently, spectral and chromatographic data indicate that the two homo-halogen dimer and the one hetero-halogen dimer are all formed in almost equal quantities. This suggests the strength of chlorine-bromine, bromine-bromine, and chlorine-chlorine interactions are of equal strength. Several positional isomers of the halogenated CAs have been tried, and similar outcomes were obtained.

Future plan: The PI plans to continue photodimerization of two non-identical alkenes based on inter-halogen. The reactions originally proposed in the ACS-PRF 2014 grant has been explored, and the inter-halogen interaction is an extension of the ideas proposed in the grant. It is expected that this work will yield results that will be included in the NSF proposal to be submitted in 2018.

Scholarly productivity and dissemination:

  • Four major grants submitted, one grant awarded (Incarvillateine Analogs as non-opioid alternative for geriatric pain management. Great Plains IDeA CTR, NIH Pilot program grant, $100,000). Preliminary data were generated from the ACS-PRF grant
  • Two review papers submitted to peer review journal – ACS PRF acknowledged in both. Israel Journal of Chemistry, and Indian Journal of Chemistry A.
  • Two talks international invited talks (Inter-American Photochemical Society 2017, and Madras Christian College, Chemistry Department, India)
  • Three talks by student supported by ACS-PRF grant ((i) 2016 Nebraska Academy of Sciences by Nga Nguyen, (ii) 2016 ACS Midwest Regional Meeting by Nga Nguyen, and 2016 Nebraska Academy of Sciences Alaine Phoebi and Megan Hunke)
  • Five poster presentations by UNK undergraduates supported by this grant (2016 ACS Midwest Regional Meeting (Experimental Biology 2017, NCUR 2017, ACS MWRM 2016 (two), American Physiological Society 2016)