A new picture of H2 activation is given by state‐of‐the‐art quantum chemical calculations of potential energy surfaces and transition states and a thorough theoretical analysis. Key factors for ...activation of H2 and other small molecules by so‐called frustrated Lewis pairs (FLP) are entrance (preparation) steps and the electric field strength inside the FLP cavity.
Dispersion‐corrected density functional theory is assessed on the new S66 and S66x8 benchmark sets for non‐covalent interactions. In total, 17 different density functionals are evaluated. Two flavors ...of our latest additive London‐dispersion correction DFT‐D3 and DFT‐D3(BJ), which differ in their short‐range damping functions, are tested. In general, dispersion corrections are again shown to be crucial to obtain reliable non‐covalent interaction energies and equilibrium distances. The corrections strongly diminish the performance differences between the functionals, and in summary most dispersion‐corrected methods can be recommended. DFT‐D3 and DFT‐D3(BJ) also yield similar results but for most functionals and intermolecular distances, the rational Becke–Johnson scheme performs slightly better. Particularly, the statistical analysis for S66x8, which covers also non‐equilibrium complex geometries, shows that the Minnesota class of functionals is also improved by the D3 scheme. The best methods on the (meta‐)GGA or hybrid‐ (meta‐)GGA level are B97‐D3, BLYP‐D3(BJ), PW6B95‐D3, MPW1B95‐D3 and LC‐ωPBE‐D3. Double‐hybrid functionals are the most accurate and robust methods, and in particular PWPB95‐D3 and B2‐PLYP‐D3(BJ) can be recommended. The best DFT‐D3 and DFT‐D3(BJ) approaches are competitive to specially adapted perturbation methods and clearly outperform standard MP2. Comparisons between S66, S22 and parts of the GMTKN30 database show that the S66 set provides statistically well‐behaved data and can serve as a valuable tool for, for example, fitting purposes or cross‐validation of other benchmark databases.
Dispersion‐corrected DFT with two different damping functions is assessed on Hobza's new S66 and S66x8 benchmark sets for non‐covalent interactions. Dispersion corrections are crucial to obtain reliable non‐covalent interaction energies and equilibrium distances. The corrections strongly diminish the performance differences between the functionals, and dispersion‐corrected DFT is competitive to wave‐function‐based methods.
High-yielding and selective prebiotic syntheses of RNA and DNA nucleotides involve UV irradiation to promote the key reaction steps and eradicate biologically irrelevant isomers. While these ...syntheses were likely enabled by UV-rich prebiotic environment, UV-induced formation of photodamages in polymeric nucleic acids, such as cyclobutane pyrimidine dimers (CPDs), remains the key unresolved issue for the origins of RNA and DNA on Earth. Here, we demonstrate that substitution of adenine with 2,6-diaminopurine enables repair of CPDs with yields reaching 92%. This substantial self-repairing activity originates from excellent electron donating properties of 2,6-diaminopurine in nucleic acid strands. We also show that the deoxyribonucleosides of 2,6-diaminopurine and adenine can be formed under the same prebiotic conditions. Considering that 2,6-diaminopurine was previously shown to increase the rate of nonenzymatic RNA replication, this nucleobase could have played critical roles in the formation of functional and photostable RNA/DNA oligomers in UV-rich prebiotic environments.
The best of 40 000: Detailed structure–activity‐relationship studies revealed key structural elements of indolin‐2‐on‐3‐spirothiazolidinones (see example) and their appropriate configuration for ...strong inhibitory activity against the pathophysiologically relevant title protein.
Quantum refinement (Q|R) of crystallographic or cryo-EM-derived structures of biomolecules within the Q|R project aims at using ab initio computations instead of library-based chemical restraints. An ...atomic model refinement requires the calculation of the gradient of the objective function. While it is not a computational bottleneck in classic refinement it is a roadblock if the objective function requires ab initio calculations. A solution to this problem adopted in Q|R is to divide the molecular system into manageable parts and do computations for these parts rather than using the whole macromolecule. This work focuses on the validation and optimization of the automatic
divide-and-conquer
procedure developed within the Q|R project. Also, we propose an atomic gradient error score that can be easily examined with common molecular visualization programs. While the tool is designed to work within the Q|R setting the error score can be adapted to similar fragmentation methods. The gradient testing tool presented here allows a priori determination of the computationally efficient strategy given available resources for the potentially time-expensive refinement process. The procedure is illustrated using a peptide and small protein models considering different quantum mechanical (QM) methodologies from Hartree–Fock, including basis set and dispersion corrections, to the modern semi-empirical method from the GFN-xTB family. The results obtained provide some general recommendations for the reliable and effective quantum refinement of larger peptides and proteins.
Many of the UV-induced phenomena observed experimentally for aqueous cytidine were lacking the mechanistic interpretation for decades. These processes include the substantial population of the ...puzzling long-lived dark state, photohydration, cytidine to uridine conversion and oxazolidinone formation. Here, we present quantum-chemical simulations of excited-state spectra and potential energy surfaces of N1-methylcytosine clustered with two water molecules using the second-order approximate coupled cluster (CC2), complete active space with second-order perturbation theory (CASPT2), and multireference configuration interaction with single and double excitation (MR-CISD) methods. We argue that the assignment of the long-lived dark state to a singlet nπ* excitation involving water-chromophore electron transfer might serve as an explanation for the numerous experimental observations. While our simulated spectra for the state are in excellent agreement with experimentally acquired data, the electron-driven proton transfer process occurring on the surface may initiate the subsequent damage in the vibrationally hot ground state of the chromophore.
Current interest in lone‐pair⋅⋅⋅π (lp⋅⋅⋅π) interactions is gaining momentum in biochemistry and (supramolecular) chemistry. However, the physicochemical origin of the exceptionally short (ca. 2.8 Å) ...oxygen‐to‐nucleobase plane distances observed in prototypical Z‐DNA CpG steps remains unclear. High‐level quantum mechanical calculations, including SAPT2+3 interaction energy decompositions, demonstrate that lp⋅⋅⋅π contacts do not result from n→π* orbital overlaps but from weak dispersion and electrostatic interactions combined with stereochemical effects imposed by the locally strained structural context. They also suggest that the carbon van der Waals (vdW) radii, originally derived for sp3 carbons, should not be used for smaller sp2 carbons attached to electron‐withdrawing groups. Using a more adapted carbon vdW radius results in these lp⋅⋅⋅π contacts being no longer of the sub‐vdW type. These findings challenge the whole lp⋅⋅⋅π concept that refers to elusive orbital interactions that fail to explain short interatomic contact distances.
Short lp⋅⋅⋅π contacts in Z‐DNA steps result from a combination of compression effects induced by a highly strained structural context and an effective van der Waals (vdW) radius of a guanine sp2 carbon atom that is estimated to be much smaller than the standard 1.70 Å vdW radius of sp3 carbons generally used to assess the sub‐vdW character of these interactions.
We have created a benchmark set of quantum chemical structure-energy data denoted as UpU46, which consists of 46 uracil dinucleotides (UpU), representing all known 46 RNA backbone conformational ...families. Penalty-function-based restrained optimizations with COSMO TPSS-D3/def2-TZVP ensure a balance between keeping the target conformation and geometry relaxation. The backbone geometries are close to the clustering-means of their respective RNA bioinformatics family classification. High-level wave function methods (DLPNO-CCSD(T) as reference) and a wide-range of dispersion-corrected or inclusive DFT methods (DFT-D3, VV10, LC-BOP-LRD, M06-2X, M11, and more) are used to evaluate the conformational energies. The results are compared to the Amber RNA bsc0χOL3 force field. Most dispersion-corrected DFT methods surpass the Amber force field significantly in accuracy and yield mean absolute deviations (MADs) for relative conformational energies of ∼0.4-0.6 kcal/mol. Double-hybrid density functionals represent the most accurate class of density functionals. Low-cost quantum chemical methods such as PM6-D3H+, HF-3c, DFTB3-D3, as well as small basis set calculations corrected for basis set superposition errors (BSSEs) by the gCP procedure are also tested. Unfortunately, the presently available low-cost methods are struggling to describe the UpU conformational energies with satisfactory accuracy. The UpU46 benchmark is an ideal test for benchmarking and development of fast methods to describe nucleic acids, including force fields.
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