Will We Witness Enzymatic or Pd-(Oligo)Peptide Catalysis in Suzuki Cross-Coupling Reactions?

Despite the development of numerous advanced ligands for Pd-catalyzed Suzuki cross-coupling reaction, the potential of (oligo)peptides serving as ligands remains unexplored. This study demonstrates via density functional theory (DFT) modeling that (oligo)peptide ligands can drive superior activity compared to classic phosphines in these reactions. The utilization of natural amino acids such as Met, SeMet, and His leads to strong binding of the Pd center, thereby ensuring substantial stability of the system. The increasing sustainability and economic viability of (oligo)peptide synthesis open new prospects for applying Pd-(oligo)peptide systems as greener catalysts. The feasibility of de novo engineering an artificial Pd-based enzyme for Suzuki cross-coupling is discussed, laying the groundwork for future innovations in catalytic systems.

Predicting 195 Pt NMR Chemical Shifts in Water-Soluble Inorganic/Organometallic Complexes with a Fast and Simple Protocol Combining Semiempirical Modeling and Machine Learning.

Water-soluble Pt complexes are the key components in medicinal chemistry and catalysis. The well-known cisplatin family of anticancer drugs and industrial hydrosylilation catalysts are two leading examples. On the molecular level, the activity mechanisms of such complexes mostly involve changes in the Pt coordination sphere. Using 195 Pt NMR spectroscopy for operando monitoring would be a valuable tool for uncovering the activity mechanisms; however, reliable approaches for the rapid correlation of Pt complex structure with 195 Pt chemical shifts are very challenging and not available for everyday research practice. While NMR shielding is a response property, molecular 3D structure determines NMR spectra, as widely known, which allows us to build up 3D structure to 195 Pt chemical shift correlations. Accordingly, we present a new workflow for the determination of lowest-energy configurational/conformational isomers based on the GFN2-xTB semiempirical method and prediction of corresponding chemical shifts with a Machine Learning (ML) model tuned for Pt complexes. The workflow was designed for the prediction of 195 Pt chemical shifts of water-soluble Pt(II) and Pt(IV) anionic, neutral, and cationic complexes with halide, NO2 - , (di)amino, and (di)carboxylate ligands with chemical shift values ranging from -6293 to 7090 ppm. The model offered an accuracy (normalized root-mean-square deviation/RMSD) of 1.08 %/145.02 ppm on the held-out test set.

Computational Approach to Molecular Catalysis by 3d Transition Metals: Challenges and Opportunities.

Computational chemistry provides a versatile toolbox for studying mechanistic details of catalytic reactions and holds promise to deliver practical strategies to enable the rational in silico catalyst design. The versatile reactivity and nontrivial electronic structure effects, common for systems based on 3d transition metals, introduce additional complexity that may represent a particular challenge to the standard computational strategies. In this review, we discuss the challenges and capabilities of modern electronic structure methods for studying the reaction mechanisms promoted by 3d transition metal molecular catalysts. Particular focus will be placed on the ways of addressing the multiconfigurational problem in electronic structure calculations and the role of expert bias in the practical utilization of the available methods. The development of density functionals designed to address transition metals is also discussed. Special emphasis is placed on the methods that account for solvation effects and the multicomponent nature of practical catalytic systems. This is followed by an overview of recent computational studies addressing the mechanistic complexity of catalytic processes by molecular catalysts based on 3d metals. Cases that involve noninnocent ligands, multicomponent reaction systems, metal-ligand and metal-metal cooperativity, as well as modeling complex catalytic systems such as metal-organic frameworks are presented. Conventionally, computational studies on catalytic mechanisms are heavily dependent on the chemical intuition and expert input of the researcher. Recent developments in advanced automated methods for reaction path analysis hold promise for eliminating such human-bias from computational catalysis studies. A brief overview of these approaches is presented in the final section of the review. The paper is closed with general concluding remarks.

Towards operando computational modeling in heterogeneous catalysis.

An increased synergy between experimental and theoretical investigations in heterogeneous catalysis has become apparent during the last decade. Experimental work has extended from ultra-high vacuum and low temperature towards operando conditions. These developments have motivated the computational community to move from standard descriptive computational models, based on inspection of the potential energy surface at 0 K and low reactant concentrations (0 K/UHV model), to more realistic conditions. The transition from 0 K/UHV to operando models has been backed by significant developments in computer hardware and software over the past few decades. New methodological developments, designed to overcome part of the gap between 0 K/UHV and operando conditions, include (i) global optimization techniques, (ii) ab initio constrained thermodynamics, (iii) biased molecular dynamics, (iv) microkinetic models of reaction networks and (v) machine learning approaches. The importance of the transition is highlighted by discussing how the molecular level picture of catalytic sites and the associated reaction mechanisms changes when the chemical environment, pressure and temperature effects are correctly accounted for in molecular simulations. It is the purpose of this review to discuss each method on an equal footing, and to draw connections between methods, particularly where they may be applied in combination.

Degradation paths of manganese-based MOF materials in a model oxidative environment: a computational study.

Stability is the key property of functional materials. In this work we investigate computationally the degradative potential of a model Mn-BTC (BTC = benzene-1,3,5-tricarboxylate) metal-organic framework (MOF) building block in aqueous solutions under oxidative conditions. Model density functional theory calculations have shown that the direct hydrolysis of the Mn-containing moieties is more difficult than their decomposition via oxidation-induced paths. While the interaction with H2O2 species is of non-covalent nature and requires O-O-bond breaking to initiate Mn-center oxidation, open-shell O2 species readily oxidize radical Mn-centers and form bonds of σ-, π-, or δ-symmetry with the metal. The oxidative transformations of di-Mn paddle-wheel carboxylate structure-forming units are accompanied with substantial distortions of the coordination polyhedra that, together with the increased Lewis acidity of the oxidized metal centers, facilitates the hydrolysis leading to the degradation of the structure at a larger scale. Whereas such a mechanism is expected to hamper the catalytic applications of such Mn-MOFs, the associated structural response to oxidizing and radical species can create a basis for the construction of Mn-MOF-based drug delivery systems with increased bio-compatibility.

Computational analysis of R-X oxidative addition to Pd nanoparticles.

Oxidative addition (OA) is a necessary step in mechanisms of widely used synthetic methodologies such as the Heck reaction, cross-coupling reactions, and the Buchwald-Hartwig amination. This study pioneers the exploration of OA of aryl halide to palladium nanoparticles (NPs), a process previously unaddressed in contrast to the activity of well-studied Pd(0) complexes. Employing DFT modeling and semi-empirical metadynamics simulations, the oxidative addition of phenyl bromide to Pd nanoparticles was investigated in detail. Energy profiles of oxidative addition to Pd NPs were analyzed and compared to those involving Pd(0) complexes forming under both ligand-stabilized (phosphines) and ligandless (amine base) conditions. Metadynamics simulations highlighted the edges of the (1 1 1) facets of Pd NPs as the key element of oxidative addition activity. We demonstrate that OA to Pd NPs is not only kinetically facile at ambient temperatures but also thermodynamically favorable. This finding accentuates the necessity of incorporating OA to Pd NPs in future investigations, thus providing a more realistic view of the involved catalytic mechanisms. These results enhance the understanding of aryl halide (cross-)coupling reactions, reinforcing the concept of a catalytic "cocktail". This concept posits dynamic interconversions between diverse active and inactive centers, collectively affecting the outcome of the reaction. High activity of Pd NPs in direct C-X activation paves the way for novel approaches in catalysis, potentially enhancing the field and offering new catalytic pathways to consider.

Fast and accurate computational modeling of adsorption on graphene: a dispersion interaction challenge.

Understanding molecular interactions of graphene is a question of key importance to design new materials and catalytic systems for practical usage. Although for small models good accuracy was demonstrated in theoretical analysis with ab initio and density functional methods, the application to real-size systems with thousands of atoms is currently hardly possible on routine bases due to the high computational cost. In the present study we report that incorporation of dispersion correction led to the principal improvement in the description of graphene systems at a semi-empirical level. The accuracy and the scope of the calculations were explored for a wide range of molecules adsorbed on graphene surfaces (H2, N2, CO, CO2, NH3, CH4, H2O, benzene, naphthalene, coronene, ovalene and cyclohexane). As a challenging parameter, the calculated adsorption energy of aromatic hydrocarbons on graphene Eads = -1.8 ± 0.1 kcal mol(-1) (per one carbon atom) at the PM6-DH2 level was in excellent agreement with the experimentally determined value of Eads = -1.7 ± 0.3 kcal mol(-1). The dispersion corrected semi-empirical method was found to be a remarkable computational tool suitable for everyday laboratory studies of real-size graphene systems. Significant performance improvement (ca. 10(3) times faster) and excellent accuracy were found as compared to the ωB97X-D density functional calculations.

1,2,4-Triazines and Calcium Carbide in the Catalyst-Free Synthesis of 2,3,6-Trisubstituted Pyridines and Their D-, 13 C-, and Doubly D2 -13 C2 -Labeled Analogues.

A novel synthetic approach to 2,3,6-trisubstituted pyridines, their 4,5-dideuterated derivatives, 4,5-13 C2 - and doubly-labeled D2 -13 C2 -pyridines has been developed using catalyst-free [4+2] cycloaddition of 1,2,4-triazines and in situ generated acetylene or labeled acetylene. Calcium carbide and water or deuterium oxide were used for the in situ generation of acetylene and dideuteroacetylene. Calcium carbide-13 C2 in the mixture with water or deuterium oxide was applied as 13 C2 -acetylene and D2 -13 C2 -acetylene source.

One-Pot and Two-Chamber Methodologies for Using Acetylene Surrogates in the Synthesis of Pyridazines and Their D-Labeled Derivatives.

Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6-disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C2 unit installation procedures in a common reaction space mode (one-pot) and distributed reaction space mode (two-chamber): (1) an interaction of 1,2,4,5-tetrazine and its acceptor-functionalized derivatives with a CaC2 -H2 O mixture performed in a two-chamber reactor led to the corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5-tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D2 O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5-dideuteropyridazines of 95-99% deuteration degree was synthesized for the first time. Quantum chemical modeling allowed to quantify the substituent effect in both synthetic pathways.

Understanding the solubilization of Ca acetylide with a new computational model for ionic pairs.

The unique reactivity of the acetylenic unit in DMSO gives rise to ubiquitous synthetic methods. We theoretically consider CaC2 solubility and protolysis in DMSO and formulate a strategy for CaC2 activation in solution-phase chemical transformations. For this, we use a new strategy for the modeling of ionic compounds in strongly coordinating solvents combining Born-Oppenheimer molecular dynamics with the DFTB3-D3(BJ) Hamiltonian and static DFT computations at the PBE0-D3(BJ)/pob-TZVP-gCP level. We modeled the thermodynamics of CaC2 protolysis under ambient conditions, taking into account its known heterogeneity and considering three polymorphs of CaC2. We give a theoretical basis for the existence of the elusive intermediate HC[triple bond, length as m-dash]C-Ca-OH and show that CaC2 insolubility in DMSO is of thermodynamic nature. We confirm the unique role of water and specific properties of DMSO in CaC2 activation and explain how the activation is realized. The proposed strategy for the utilization of CaC2 in sustainable organic synthesis is outlined.