College of Chemistry

Abstract: This Roadmap article provides a succinct, comprehensive overview of the state of electronic structure (ES) methods and software for molecular and materials simulations. Seventeen distinct sections collect insights by 51 leading scientists in the field. Each contribution addresses the status of a particular area, as well as current challenges and anticipated future advances, with a particular eye towards software related aspects and providing key references for further reading. Foundational sections cover density functional theory and its implementation in real-world simulation frameworks, Green’s function based many-body perturbation theory, wave-function based and stochastic ES approaches, relativistic effects and semiempirical ES theory approaches. Subsequent sections cover nuclear quantum effects, real-time propagation of the ES, challenges for computational spectroscopy simulations, and exploration of complex potential energy surfaces. The final sections summarize practical aspects, including computational workflows for complex simulation tasks, the impact of current and future high-performance computing architectures, software engineering practices, education and training to maintain and broaden the community, as well as the status of and needs for ES based modeling from the vantage point of industry environments. Overall, the field of ES software and method development continues to unlock immense opportunities for future scientific discovery, based on the growing ability of computations to reveal complex phenomena, processes and properties that are determined by the make-up of matter at the atomic scale, with high precision.

Identification of the breaking point for the chemical bond is essential for our understanding of chemical reactivity. The current consensus is that a point of maximal electron delocalization along the bonding axis separates the different bonding regimes of reactants and products. This maximum transition point has been investigated previously through the total position spread and the bond-parallel components of the static polarizability tensor for describing covalent bond breaking. In this paper, we report that the first-order change of the Wiberg and Mayer bond index with respect to the reaction coordinate, the bond flux, is similarly maximized and is nearly equivalent with the bond breaking points determined by the bond-parallel polarizability. We investigate the similarites and differences between the two bonding metrics for breaking the nitrogen triple bond, twisting around the ethene double bond, and a set of prototypical reactions in the hydrogen combustion reaction network. The Wiberg-Mayer bond flux provides a simpler approach to calculating the point of bond dissociation and formation and can yield greater chemical insight through bond specific information for certain reactions where multiple bond changes are operative.

Camphor and related monoterpenoid natural products have served as versatile "chiral pool" materials in organic chemistry for over half a century. Historically, many researchers have used a variety of transformations involving orchestrated rearrangements of the bornane skeleton to functionalize the camphor framework, expanding the utility of this chiral building block. Recent developments in C-H functionalization methodologies provide myriad opportunities to derivatize the camphor framework in a selective and predictable fashion. In this review, a short summary of the methods for functionalization of the camphor scaffold using rearrangement chemistry is provided followed by a discussion of emerging methods for directed C-H functionalizations that provide diverse new ways to derivatize the camphor framework.

Given its relevance across numerous fields, reductive amination is one of the oldest and most widely used methods for amine synthesis. As a cornerstone of synthetic chemistry, it has largely remained unchanged since its discovery over a century ago. Herein, we report the mechanistically driven development of a complementary reaction, which reductively aminates the C-C σ-bond of carbonyls, not the carbonyl C-O π-bond, generating value-added linear and cyclic 3° amines in a modular fashion. Critical to our success were mechanistic insights that enabled us to modulate the resting state of a borane catalyst, minimize deleterious disproportionation of a hydroxylamine nitrogen source, and control the migratory selectivity of a key nitrenoid reactive intermediate. Experiments support the reaction occurring through a reductive amination/reductive Stieglitz cascade, via a ketonitrone, which can be interrupted under catalyst control to generate valuable N,N-disubstituted hydroxylamines. The method reported herein enables net transformations that would otherwise require lengthy synthetic sequences using pre-existing technologies. This is highlighted by its application to a two-step protocol for the valorization of hydrocarbon feedstocks, the late-stage C-C amination of complex molecules, diversity-oriented synthesis of isomeric amines from a single precursor, and transposition of nitrogen to different positions within a heterocycle.

Catalysis of multicomponent transformations requires controlled assembly of reactants within the active site. Supramolecular scaffolds possess synthetic microenvironments that enable precise modulation over noncovalent interactions (NCIs) engaged by reactive, encapsulated species. While molecular properties that describe the behavior of single guests in host cavities have been studied extensively, multicomponent transformations remain challenging to design and deploy. Here, simple univariate regression and threshold analyses are employed to model reactivity in a cascade reduction of azaarenes catalyzed by water-soluble metal organic cages. Yield and stereoselectivity models help deduce unknown mechanisms of reactivity by the multicomponent, host-guest complexes. Furthermore, a comprehensive model is established for NCIs driving stereoselectivity in the reported host-guest adducts.

Ammonium acetate is widely used in native mass spectrometry to provide adequate ionic strength without adducting to protein ions, but different ions can preferentially stabilize or destabilize the native form of proteins in solution. The stability of bovine serum albumin (BSA) was investigated in 50 mM solutions of a variety of salts using electrospray emitters with submicron tips to desalt protein ions. The charge-state distribution of BSA is narrow (+14 to +18) in ammonium acetate (AmmAc), whereas it is much broader (+13 to +42) in solutions containing sodium acetate (NaAc), ammonium chloride (AmmCl), potassium chloride (KCl), and sodium chloride (NaCl). The average charge state and percent of unfolded protein increase in these respective solutions, indicating greater extents of protein destabilization and conformational changes. In contrast, no high charge states of either bovine carbonic anhydrase II or IgG1 were formed in AmmAc or NaCl despite their similar melting temperatures to BSA, indicating that the presence of unfolded BSA in some of these solutions is not an artifact of the electrospray ionization process. The charge states formed from the nonvolatile salt solutions do not change significantly for up to 7 min of electrospray, but higher charging occurs after 10 min, consistent with solution acidification. Formation of unfolded BSA in NaAc but not in AmmAc indicates that the cation identity, not acidification, is responsible for structural differences in these two solutions. Temperature-dependent measurements show both increased charging and aggregation at lower temperatures in NaCl:Tris than in AmmAc, consistent with lower protein stability in the former solution. These results are consistent with the order of these ions in the Hofmeister series and indicate that data on protein stability in AmmAc may not be representative of solutions containing nonvolatile salts that are directly relevant to biology.

We investigate the evaporation of trace amounts of helium solvated in liquid water using molecular dynamics simulations and theory. Consistent with experimental observations, we find a super-Maxwellian distribution of kinetic energies of evaporated helium. This excess of kinetic energy over typical thermal expectations is explained by an effective continuum theory of evaporation based on a Fokker-Planck equation, parametrized molecularly by a potential of mean force and position-dependent friction. Using this description, we find that helium evaporation is strongly influenced by the friction near the interface, which is anomalously small near the Gibbs dividing surface due to the ability of the liquid-vapor interface to deform around the gas particle. Our reduced description provides a mechanistic interpretation of trace gas evaporation as the motion of an underdamped particle in a potential subject to a viscous environment that varies rapidly across the air-water interface. From it we predict the temperature dependence of the excess kinetic energy of evaporation, which is yet to be measured.

Solid-state high harmonic generation (sHHG) spectroscopy is an emerging ultrafast technique for studying key material properties such as electronic structure at and away from equilibrium. sHHG anisotropy measurements, where sHHG spectra are recorded depending on the driving electric field relative to the crystal lattice, have become a powerful tool for studying crystal symmetries. Previous works on two-dimensional materials and other quantum materials have often used substrate-supported samples, assuming that all sHHG signals originate from the sample due to the relatively large bandgap of the substrate. While this assumption is generally reasonable, we show that some sHHG emissions from commonly used substrates can occur at moderate intensities of the sHHG driving field. In addition, we show that it is essential to consider not only the sHHG yield from a substrate but also its angular dependence relative to the material of interest. Specifically, in this work, the power-dependent and polarization angle-resolved sHHG emissions of fused silica, calcium fluoride, diamond, and sapphire of two different crystalline qualities and orientations are compared using a mid-infrared (MIR) driving field. This empirical characterization aims to guide the substrate selection for sHHG studies of novel materials to minimize the misattribution and interference of substrate-related sHHG emissions, which opens the possibility to study a wider array of materials.

A coherent vibrational wavepacket is launched and manipulated in the symmetric stretch (a1) mode of CBr4, by impulsive stimulated Raman scattering (ISRS) from nonresonant 400 nm laser pump pulses with various peak intensities on the order of tens of 1012 W/cm2. Extreme ultraviolet (XUV) attosecond transient absorption spectroscopy (ATAS) records the wavepacket dynamics as temporal oscillations in XUV absorption energy at the bromine M4,5 3d3/2,5/2 edges around 70 eV. The results are augmented by nuclear time-dependent Schrödinger equation simulations. Slopes of the (Br 3d3/2,5/2)-110a1* core-excited state potential energy surface (PES) along the a1 mode are calculated to be -9.4 eV/Å from restricted open-shell Kohn-Sham calculations. Using analytical relations derived for the small-displacement limit and the calculated slopes of the core-excited state PES, a deeper insight into the vibrational dynamics is obtained by retrieving the experimental excursion amplitude of the vibrational wavepacket and the amount of population transferred to the vibrational first-excited state as a function of pump-pulse peak intensity. Experimentally, the results show that XUV ATAS is capable of resolving oscillations in the XUV absorption energy on the order of a few to tens of meV with tens of femtosecond time precision. This corresponds to change in C-Br bond length on the order of 10-4 to 10-3 Å. The results and the analytic relationships offer a clear physical picture, on multiple levels of understanding, of how the pump-pulse peak intensity controls the vibrational dynamics launched by nonresonant ISRS in the small-displacement limit.

The photochemical generation of nicotinamide cofactor 1,4-NADH, facilitated by inorganic photosensitizers, emerges as a promising model system for investigating charge transfer phenomena at the interface of semiconductors and bacteria, with implications for enhancing photosynthetic biohybrid systems (PBSs). However, extant semiconductor nanocrystal model systems suffer from achieving optimal conversion efficiency under visible light. This study investigates quasi-one-dimensional CdS nanorods as superior light absorbers, surface modified with catalyst Cp*Rh(4,4'-COOH-bpy)Cl₂ to produce enzymatically active NADH. This model subsystem facilitates easy product isolation and achieves a turnover frequency (TOF) of 175 h^-1, one of the highest efficiencies reported for inorganic photosensitizer-based nicotinamide cofactor generation. Charge transfer kinetics, fundamental for catalytic solar energy conversion, range from 10⁶ to 10⁸ s^-1 for this system highlighting the superior electron transfer capabilities of NRs. This model ensures efficient cofactor production and offers critical insights into advancing systems that mimic natural photosynthesis for sustainable solar-to-chemical synthesis.