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Cold water benthic environments are a prolific source of structurally diverse molecules with a range of bioactivities against human disease. Specimens of a previously chemically unexplored soft coral, Duva florida, were collected during a deep-sea cruise that sampled marine invertebrates along the Irish continental margin in 2018. Tuaimenal A (1), a cyclized merosesquiterpenoid representing a new carbon scaffold with a highly substituted chromene core, was discovered through exploration of the soft coral secondary metabolome via NMR-guided fractionation. The absolute configuration was determined through vibrational circular dichroism. Functional biochemical assays and in silico docking experiments found tuaimenal A selectively inhibits the viral main protease (3CLpro) of SARS-CoV-2.

The quantum chemistry community has developed analytic forces for approximate electronic excited states to enable walking on excited state potential energy surfaces (PES). One can thereby computationally characterize excited state minima and saddle points. Always implicit in using this machinery is the fact that an excited state PES only exists within the realm of the Born-Oppenheimer approximation, where the nuclear and electronic degrees of freedom separate. This work demonstrates through ab initio calculations and simple nonadiabatic dynamics that some excited state minimum structures are fantastical: they appear to exist as stable configurations only as a consequence of the PES construct, rather than being physically observable. Each fantastical structure exhibits an unphysically high predicted harmonic frequency and associated force constant. This fact can serve as a valuable diagnostic of when an optimized excited state structure is non-observable. The origin of this phenomenon can be attributed to the coupling between different electronic states. As PESs approach one another, the upper surface can form a minimum that is very close to a near-touching point. The force constant, evaluated at this minimum, relates to the strength of the electronic coupling rather than to any characteristic excited state vibration. Nonadiabatic dynamics results using a Landau-Zener model illustrate that fantastical excited state structures have extremely short lifetimes on the order of a few femtoseconds. Their appearance in a calculation signals the presence of a nearby conical intersection through which the system will rapidly cross to a lower surface. [ABSTRACT FROM AUTHOR]

Liquid-jet photoemission spectroscopy (LJ-PES) directly probes the electronic structure of solutes and solvents. It also emerges as a novel tool to explore chemical structure in aqueous solutions, yet the scope of the approach has to be examined. Here, we present a pH-dependent liquid-jet photoelectron spectroscopic investigation of ascorbic acid (vitamin C). We combine core-level photoelectron spectroscopy and ab initio calculations, allowing us to site-specifically explore the acid–base chemistry of the biomolecule. For the first time, we demonstrate the capability of the method to simultaneously assign two deprotonation sites within the molecule. We show that a large change in chemical shift appears even for atoms distant several bonds from the chemically modified group. Furthermore, we present a highly efficient and accurate computational protocol based on a single structure using the maximum-overlap method for modeling core-level photoelectron spectra in aqueous environments. This work poses a broader question: to what extent can LJ-PES complement established structural techniques such as nuclear magnetic resonance? Answering this question is highly relevant in view of the large number of incorrect molecular structures published. [ABSTRACT FROM AUTHOR]

In this work, we assess the accuracy of the Bethe–Salpeter equation (BSE) many-body Green's function formalism, adopting the eigenvalue-self-consistent evGW exchange–correlation kernel, for the calculation of the excited-state (μES) and excess dipole moments (Δμ), the latter ones being the changes of dipole amplitude between the ground and excited states (ES), in organic dyes. We compare the results obtained with wave-function methods [ADC(2), CC2, and CCSD], time-dependent density functional theory (TD-DFT), and BSE/evGW levels of theory. First, we compute the evolution of the dipole moments of the two lowest singlet excited states of 4-(dimethylamino)benzonitrile (DMABN) upon twisting of the amino group. Next, we use a set of 25 dyes having ES characters ranging from locally excited to charge transfer to determine both μES and Δμ. For DMABN our results show that BSE/evGW provides Δμ values closer to the CCSD reference and more consistent trends than TD-DFT. Moreover, a statistical analysis of both Δμ and μES for the set of 25 dyes shows that the BSE/evGW accuracy is comparable or sometimes slightly better than that of TD-M06-2X and TD-CAM-B3LYP, BSE/evGW outperforming TD-DFT in challenging cases (zwitterionic and cyanine transitions). Finally, the starting point dependency of BSE/evGW seems to be larger for Δμ, ES dipoles, and oscillator strengths than for transition energies. [ABSTRACT FROM AUTHOR]