Unraveling Polymorphic Control in the Solid-State [2+2] Cycloaddition of Vitamin K3: Insights from Single-Crystal Irradiation

Year: 2025

Authors: Loprete F., Pandolfi L., Giunchi A., Pandolfi S., d’Agostino S., Tarroni R., Graziosi P., Della Valle RG., Salzillo T., Venuti E.

Autors Affiliation: Univ Bologna, Dipartimento Chim Ind Toso Montanari, I-40129 Bologna, Italy; CNR Natl Inst Opt INO, Via Branze 45, I-25123 Brescia, Italy; Univ Bologna, Dipartimento Chim Giacomo Ciamician, I-40126 Bologna, Italy; CNR Inst Nanostruct Mat ISMN, I-40129 Bologna, Italy.

Abstract: The solid-state [2 + 2] cycloaddition of vitamin K3 (VK3) polymorphs has been systematically reexamined, overcoming the limitations of powder-based studies by focusing on single-crystal behavior. Using THz micro-Raman and FTIR-ATR vibrational spectroscopies combined with X-ray diffraction and solid-state density functional theory (DFT) calculations, we unveil distinct photoreactivity and stereoselectivity in both polymorphs. Monochromatic irradiation at the absorption tail preserved the crystal integrity, enabling a detailed investigation of the reaction outcomes. While both polymorphs undergo photoreaction, their transformations proceed via distinct crystal-to-crystal processes, yielding cis-syn and cis-anti dimers selectively. The photochemical pathway to the formation of the cis-isomers is analyzed by quantum mechanical calculations. These findings highlight the critical role of polymorphism in solid-state photochemistry while questioning the conventional dichotomy between defect-driven and purely topochemical mechanisms.

Journal/Review: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Volume: 147 (24)      Pages from: 21109  to: 21120

More Information: We thank Prof. Michele Mancinelli for his assistance with the HPLC measurements. We acknowledge funding from the European Union-Next-Generation EU via the Italian call PRIN 2022, Project No. 2022XZ2ZM8, POLYPHON. T.S. thanks the Programma per Giovani Ricercatori Rita Levi Montalcini year 2020 (Grant No. PGR20QN52R) of the Italian Ministry of University and Research (MUR) for the financial support. We acknowledge funding for the VASP license from the company M.M.B. s.r.l., Faenza (RA) Italy.
KeyWords: X-ray Structures; Phase-change; Photodimerization; Kinetics; Mechanism; Photochemistry; Nucleation; Acids
DOI: 10.1021/jacs.5c06303