In Silico Discovery of Multistep Chemistry Initiated by a Conical Intersection: The Challenging Case of Donor–Acceptor Stenhouse Adducts

Abstract

Detailed mechanistic understanding of multistep chemical reactions triggered by internal conversion via a conical intersection is a challenging task that emphasizes limitations in theoretical and experimental techniques. Hypothesis-driven methodologies (e.g. characterization of critical points and biased molecular dynamics) are commonly employed to explore chemical space and simulate reaction events. In this contribution, we present a discovery-based, hypothesis-free computational approach based on first principles molecular dynamics to discover and refine the switching mechanism of Donor-Acceptor Stenhouse Adducts (DASAs). Using state-of-the-art graphical processing units-enabled electronic structure calculations we performed in total ~2ns of adiabatic and non-adiabatic ab initio molecular dynamics discovering a) critical intermediates that are involved in the open-to-closed transformation, b) several competing pathways which lower the overall switching yield, and c) key elements for future design strategies. Our dynamics describe the natural evolution of both the nuclear and electronic degrees of freedom that govern the interconversion between DASA ground state intermediates exposing significant elements for the future design strategies of molecular switches.

Donor–Acceptor Stenhouse Adduct Displaying Reversible Photoswitching in Water and Neuronal Activity

“…The DASA switching mechanism has been elucidated by combining experimental and theoretical approaches, revealing its intermediate steps and the guidelines to design DASA photoswitches. − These studies have identified different isomerization and rotation steps, followed by an electrocyclization and proton transfer mechanism that leads to the final cyclized form of the compound . Recently, insights into a three-stage single photochrome photoswitching system were obtained with a DASA derivative capable of addressing multiple molecular states .…”

Donor–Acceptor Stenhouse Adduct‐Polydimethylsiloxane‐Conjugates for Enhanced Photoswitching in Bulk Polymers

“…[ 8–10 ] DASAs undergo a visible light‐induced, colored to colorless, open triene to closed cyclopentenone isomerization that is thermally reversible. [ 11–15 ] Their tunable absorption in the spectral range between 450 and 750 nm [ 16–21 ] enables DASA activation at wavelengths suitable for biological applications. [ 22 ] DASA‐functionalized polymers were already investigated for potential applications in a number of areas ranging from photo‐/hydrochromic, [ 23–25 ] photopatternable, [ 26–29 ] or wettability switching [ 30–34 ] surfaces and objects, to smart drug delivery, [ 35–40 ] chemical sensing, [ 41–45 ] and photoactuation.…”

Enhanced Sampling Aided Design of Molecular Photoswitches

“…In particular, the photoswitching mechanism of DASA-based systems starts with an actinic step (E/Z photoisomerization) but is followed by a multitude of competing thermal pathways involving 4p electrocyclization, bond rotation and proton transfer. [23][24][25][26][27][28][29][30][31][32][33][34][35] In our Raucci, U and Sanchez, D. M et al -Enhanced Sampling Aided Design 3 recent work [29][30] we showed for the first time the natural evolution of the nuclear wavepacket relaxing through conical intersections via ab initio nonadiabatic and adiabatic quantum molecular dynamics (Fig. 1).…”