Correction: Simple, accurate, adjustable-parameter-free prediction of NMR shifts for molecules in solution.

Correction for 'Simple, accurate, adjustable-parameter-free prediction of NMR shifts for molecules in solution' by Emlyn M. Hoyt et al., Phys. Chem. Chem. Phys., 2023, 25, 9952-9957, https://doi.org/10.1039/D3CP00721A.

A new lysine biosynthetic enzyme from a bacterial endosymbiont shaped by genetic drift and genome reduction.

The effect of population bottlenecks and genome reduction on enzyme function is poorly understood. Candidatus Liberibacter solanacearum is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid-a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the function of Ca. L. solanacearum dihydrodipicolinate synthase (CLsoDHDPS), which catalyzes the committed branchpoint reaction in diaminopimelate and lysine biosynthesis. We demonstrate that CLsoDHDPS is expressed in Ca. L. solanacearum and expression is increased ~2-fold in the insect host compared to in planta. CLsoDHDPS has decreased thermal stability and increased aggregation propensity, implying mutations have destabilized the enzyme but are compensated for through elevated chaperone expression and a stabilized oligomeric state. CLsoDHDPS uses a ternary-complex kinetic mechanism, which is to date unique among DHDPS enzymes, has unusually low catalytic ability, but an unusually high substrate affinity. Structural studies demonstrate that the active site is more open, and the structure of CLsoDHDPS with both pyruvate and the substrate analogue succinic-semialdehyde reveals that the product is both structurally and energetically different and therefore evolution has in this case fashioned a new enzyme. Our study suggests the effects of genome reduction and genetic drift on the function of essential enzymes and provides insights on bacteria-host co-evolutionary associations. We propose that bacteria with endosymbiotic lifestyles present a rich vein of interesting enzymes useful for understanding enzyme function and/or informing protein engineering efforts.

Redox Behaviour and Redox Potentials of Dyes in Aqueous Buffers and Protic Ionic Liquids.

Organic dyes hold promise as inexpensive electrochemically-active building blocks for new renewable energy technologies such as redox-flow batteries and dye-sensitised solar cells, especially if they display high oxidation and/or low reduction potentials in cheap, non-flammable solvents such as water or protic ionic liquids. Systematic computational and experimental characterisation of a representative selection of acidic and basic dyes in buffered aqueous solutions and propylammonium formate confirm that quinoid-type mechanisms impart electrochemical reversibility for the majority of systems investigated, including quinones, fused tricyclic heteroaromatics, indigo carmine and some aromatic nitrogenous species. Conversely, systems that generate longlived radical intermediates - arylmethanes, hydroquinones at high pH, azocyclic systems - tend to display irreversible electrochemistry, likely undergoing ring-opening, dimerisation and/or disproportionation reactions.

Simple, accurate, adjustable-parameter-free prediction of NMR shifts for molecules in solution.

Accurate prediction of NMR shifts is invaluable for interpreting and assigning NMR spectra, especially for complex applications such as determining the identity of unknown substances or resolving stereochemical assignments. Statistical linear regression models have proven effective for accurately correlating density functional theory predictions of chemical shieldings with experimentally-measured shifts, but lack transferability - they must be reparameterised using a reasonably extensive training set at each level of theory and for each choice of NMR solvent. We have previously introduced a novel two-point "shift-and-scale" correction procedure for gas phase shieldings that overcomes these limitations without significant loss of accuracy. In this work, we demonstrate that this approach is equally applicable for predicting solution-phase shifts from computed gas phase shieldings, using acetaldehyde as an experimentally and computationally convenient reference system. We also present all of the required experimental reference data to enable this approach to be used for any target analyte in a range of commonly used NMR solvents (chloroform, dichloromethane, acetonitrile, methanol, acetone, DMSO, D2O, benzene, pyridine).

Acid-Base Chemistry Provides a Simple and Cost-Effective Route to New Redox-Active Ionic Liquids.

Redox-active ionic liquids (RAILs) hold great promise as high density electrochemical energy storage materials, but are hampered by high costs and low bulk conductivities. In this work, we introduce and electrochemically characterise novel redox-active protic ionic liquids (RAPILs) formed by acid-base neutralisation from cheap and plentiful starting materials. We also demonstrate a novel RAIL-in-IL solvent system for electrochemical characterisation of RAPILs, which enables efficient and cost-effective determination of redox potentials and screening for electrochemical reversibility. Of the redox-active ionic liquids tested in this work, only propylammonium 4-nitrophenylacetate demonstrates completely reversible electrochemistry and preservation of ionic character upon redox cycling under acidic or neutral conditions. Propylammonium 2,5-dihydroxyphenyl-carboxylate also demonstrates two reversible redox processes, but is unstable to oxidation at 0.27 V vs Ag (-0.14 V vs Fc), most likely forming an uncharged benzoquinone species. Using the lessons learned from this prototypical set of RAPILs, we propose design criteria to guide future experimental and computational work.

The structure of His-tagged Geobacillus stearothermophilus purine nucleoside phosphorylase reveals a `spanner in the works'.

The 1.72 Šresolution structure of purine nucleoside phosphorylase from Geobacillus stearothermophilus, a thermostable protein of potential interest for the biocatalytic synthesis of antiviral nucleoside compounds, is reported. The structure of the N-terminally His-tagged enzyme is a hexamer, as is typical of bacterial homologues, with a trimer-of-dimers arrangement. Unexpectedly, several residues of the recombinant tobacco etch virus protease (rTEV) cleavage site from the N-terminal tag are located in the active site of the neighbouring subunit in the dimer. Key to this interaction is a tyrosine residue, which sits where the nucleoside ring of the substrate would normally be located. Tag binding appears to be driven by a combination of enthalpic, entropic and proximity effects, which convey a particularly high affinity in the crystallized form. Attempts to cleave the tag in solution yielded only a small fraction of untagged protein, suggesting that the enzyme predominantly exists in the tag-bound form in solution, preventing rTEV from accessing the cleavage site. However, the tagged protein retained some activity in solution, suggesting that the tag does not completely block the active site, but may act as a competitive inhibitor. This serves as a warning that it is prudent to establish how affinity tags may affect protein structure and function, especially for industrial biocatalytic applications that rely on the efficiency and convenience of one-pot purifications and in cases where tag removal is difficult.

A new double-reference correction scheme for accurate and efficient computation of NMR chemical shieldings.

Using an extensive set of benchmark geometric data and absolute NMR chemical shieldings for gas phase molecules compiled from the literature, we introduce and test a novel shift-and-scale correction scheme for bringing computed values into closer agreement with experiment. Our approach requires only one additional reference calculation relative to existing methods for computing chemical shifts, and all reference species are small molecules whose absolute nuclear shieldings can be easily obtained, both computationally and experimentally. We demonstrate that our approach is capable of correcting for errors due to choice of electronic structure method and basis set, vibrational averaging effects, and scalar relativistic effects, but cannot account for the influence that heavy atoms have on the chemical shieldings of neighbouring light atoms, via spin-orbit coupling. We particularly recommend using our approach in conjunction with nuclear shieldings computed at DFT optimized geometries, employing hybrid functionals with moderate-to-high quality atomic orbital basis sets, e.g. pc-2.

Structures and Spectra of Halide Hydrate Clusters in the Solid State: A Link between the Gas Phase and Solution State.

This Review describes and assesses known solid-state examples of halide hydrates that are discrete in nature. Most of these are chloride hydrates, and most discrete clusters are dihalides, with very few mono- or multi-halide species found in the solid state. Polymeric chloride hydrates, on the other hand, are mostly 2D layered structures. We also observe that there is a gap in the chloride:water ratio between 8-20 waters per chloride. Isolated clusters can be found with 1-3 waters per chloride, 2D layers with 2-8 waters, and 3D semiclathrates with 20-38 waters. However, 1D chains comprise only 1-2 waters per chloride. [Cl(H2 O)]- is the only species found in both the solid state and gas phase and is also the only halide hydrate with a free OH group. Infrared spectra in the ν(OH) region are distinctive and useful for identification. Agreement between computed (gas phase) and experimentally-observed solid state structures and their vibrational spectra gives us confidence that discrete halide hydrate species observed in the solid state provide a useful link between gas phase species and structural motifs of halide hydrates in solution, especially microsolvated ion-pairs.

Discrete Oligomers and Polymers of Chloride Monohydrate Can Form in Encapsulated Environments: Structures and Infrared Spectra of [Cl4 (H2 O)4 ]4- and {[Cl(H2 O)]- }∞.

A discrete tetrachloride tetrahydrate cluster, [Cl4 (H2 O)4 ]4- , was obtained with a partially-fluorinated triaminocyclopropenium cation, [C3 (N(CH2 CF3 )2 )(NEt2 )(NPr2 )]+ . The cluster consists of a [Cl2 (H2 O)2 ]2- square with each Cl- coordinated by another H2 O bridged to another Cl- . A 1D polymer of chloride monohydrate, {[Cl(H2 O)]- }∞ , was obtained with [C3 (N(CH2 CF3 )2 )2 (NBuMe)]+ . The tetrameric and polymeric structures were found to be computationally-unstable in the gas phase which indicates that an encapsulated environment is essential for their isolation. DFT and DFTB calculations were carried out on gas-phase [Cl4 (H2 O)4 ]4- to assist the infrared assignments. Anharmonically-corrected B3LYP transition frequencies were in close agreement with experiment, but DFTB models were only appropriate for qualitative interpretation. Solid-state DFTB calculations allowed the vibrational modes to be assigned. The results found are consistent with "discrete" chloride hydrates.

New atoms-in-molecules dispersion models for use in ab initio derived force fields.

Recently, substantial research efforts have gone into bridging the accuracy-efficiency gap between parameterized force field models and quantum chemical calculations by extracting molecule-specific force fields directly from ab initio data in a robust and automated manner. One of the challenging aspects is deriving localized atomic polarizabilities for pairwise distributed dispersion models. The Tkatchenko-Scheffler model is based upon correcting free-atom C6 coefficients according to the square of the ratio of the atom-in-molecule volume to the free-atom volume. However, it has recently been shown that a more accurate relationship can be found if static atomic polarizabilities are also taken into account. Using this relationship, we develop two modified Tkatchenko-Scheffler dispersion models and benchmark their performance against SAPT2+3 reference data and other commonly used dispersion models.

Optical Detection of CoV-SARS-2 Viral Proteins to Sub-Picomolar Concentrations.

The emergence of a new strain of coronavirus in late 2019, SARS-CoV-2, led to a global pandemic in 2020. This may have been preventable if large scale, rapid diagnosis of active cases had been possible, and this has highlighted the need for more effective and efficient ways of detecting and managing viral infections. In this work, we investigate three different optical techniques for quantifying the binding of recombinant SARS-CoV-2 spike protein to surface-immobilized oligonucleotide aptamers. Biolayer interferometry is a relatively cheap, robust, and rapid method that only requires very small sample volumes. However, its detection limit of 250 nM means that it is not sensitive enough to detect antigen proteins at physiologically relevant levels (sub-pM). Surface plasmon resonance is a more sensitive technique but requires larger sample volumes, takes longer, requires more expensive instrumentation, and only reduces the detection limit to 5 nM. Surface-enhanced Raman spectroscopy is far more sensitive, enabling detection of spike protein to sub-picomolar concentrations. Control experiments performed using scrambled aptamers and using bovine serum albumin as an analyte show that this apta-sensing approach is both sensitive and selective, with no appreciable response observed for any controls. Overall, these proof-of-principle results demonstrate that SERS-based aptasensors hold great promise for development into rapid, point-of-use antigen detection systems, enabling mass testing without any need for reagents or laboratory expertise and equipment.

Are "Bright-State" Models Appropriate for Analyzing Fermi-Coupled Bands in Molecular Vibrational Spectra?

Bright-state models are often applied to "deperturb" Fermi-coupled bands in molecular vibrational spectra, in cases where a harmonically forbidden transition "borrows" intensity from an energetically nearby allowed transition. However, forbidden transitions can also acquire intensity through anharmonic couplings on the potential energy surface ("mechanical anharmonicity") or dipole moment surface ("electrical anharmonicity") that are not accounted for within the bright-state model. In this work, we compare deperturbation shifts obtained by analysis of experimental data with those predicted using the bright-state model, for a series of discrete encapsulated chloride hydrate isotopomers. Predicted band center shifts and Fermi coupling matrix elements obtained using the bright-state model are larger than those estimated from experimental data.

Hydrogen Delocalization in an Asymmetric Biomolecule: The Curious Case of Alpha-Fenchol.

Rotational microwave jet spectroscopy studies of the monoterpenol α-fenchol have so far failed to identify its second most stable torsional conformer, despite computational predictions that it is only very slightly higher in energy than the global minimum. Vibrational FTIR and Raman jet spectroscopy investigations reveal unusually complex OH and OD stretching spectra compared to other alcohols. Via modeling of the torsional states, observed spectral splittings are explained by delocalization of the hydroxy hydrogen atom through quantum tunneling between the two non-equivalent but accidentally near-degenerate conformers separated by a low and narrow barrier. The energy differences between the torsional states are determined to be only 16(1) and 7(1) cm-1hc for the protiated and deuterated alcohol, respectively, which further shrink to 9(1) and 3(1) cm-1hc upon OH or OD stretch excitation. Comparisons are made with the more strongly asymmetric monoterpenols borneol and isopinocampheol as well as with the symmetric, rapidly tunneling propargyl alcohol. In addition, the third-in contrast localized-torsional conformer and the most stable dimer are assigned for α-fenchol, as well as the two most stable dimers for propargyl alcohol.

On the separability of large-amplitude motions in anharmonic frequency calculations.

Nuclear vibrational theories based upon the Watson Hamiltonian are ubiquitous in quantum chemistry, but are generally unable to model systems in which the wavefunction can delocalise over multiple energy minima, i.e. molecules that have low-energy torsion and inversion barriers. In a 2019 Chemical Reviews article, Puzzarini et al. note that a common workaround is to simply decouple these problematic modes from all other vibrations in the system during anharmonic frequency calculations. They also point out that this approximation can be "ill-suited", but do not quantify the errors introduced. In this work, we present the first systematic investigation into how separating out or constraining torsion and inversion vibrations within potential energy surface (PES) expansions affects the accuracy of computed fundamental wavenumbers for the remaining vibrational modes, using a test set of 19 tetratomic molecules for which high quality analytic potential energy surfaces and fully-coupled anharmonic reference fundamental frequencies are available. We find that the most effective and efficient strategy is to remove the mode in question from the PES expansion entirely. This introduces errors of up to +10 cm-1 in stretching fundamentals that would otherwise couple to the dropped mode, and ±5 cm-1 in all other fundamentals. These errors are approximately commensurate with, but not necessarily additional to, errors due to the choice of electronic structure model used in constructing spectroscopically accurate PES.

A Series of Discrete Dichloride Dihydrates: Characterisation and Symmetry Effects.

A series of three discrete dichloride dihydrates [Cl2 (H2 O)2 ]2- have been isolated with different triaminocyclopropenium (TAC) cations and with different crystallographic symmetries. The cluster exhibits D2h symmetry with the tris(dimethylamino)cyclopropenium cation [C3 (NMe2 )3 ]+ , C2h symmetry with the fluorinated cation [C3 (N(CH2 CF3 )2 )(NBu2 )2 ]+ (containing two 2,2,2-trifluoroethyl substituents) and C2v symmetry with the more fluorinated [C3 (N(CH2 CF3 )2 )2 (NBu2 )]+ cation. The effect of symmetry on the infrared spectra of the dichloride ion-pair clusters, as well as deuterated analogues, has been investigated. The D2h - and C2h -symmetric clusters each exhibit two stretching bands in the infrared at 3427 and 3368 cm-1 for D2h symmetry and 3444 and 3392 cm-1 for C2h symmetry, whereas the C2v -symmetric cluster exhibits three bands at 3475, 3426 and 3373 cm-1 . Computational studies were carried out on a [Cl2 (H2 O)2 ]2- cluster with C2v symmetry to aid the infrared band assignments.

Temperature-Dependent Blue Shifting of O-H Stretching Frequencies in Crystalline Cellulose Explained.

Increasing the temperature of a chemical system generally causes covalent bonds to lengthen and weaken, often the first step in initiating chemical reactions. However, for some hydrogen-bonded systems, infrared (IR) spectroscopy measurements reveal that covalent O-H bonds actually strengthen and therefore shorten when heated. In 1957, Finch and Lippincott proposed a simple one-dimensional (1D) model to explain this effect, in which thermal excitation of intermolecular stretching modes leads to lengthening and weakening of intermolecular O-H···O hydrogen bonds, thereby indirectly strengthening the associated covalent O-H bonds. Taking cellulose (an infinitely repeating polymer of d-glucose) as an example, we use molecular dynamics modeling to show that the same mechanism is responsible for temperature-dependent blue shifting of O-H stretching bands in IR spectra of carbohydrate biopolymers, except that interchain hydrogen bonds are weakened by thermal excitation of chain-separation modes, while intrachain hydrogen bonds are weakened by thermally induced changes in ring puckering and orientation of ring substituents but not reorientation of glucose units relative to one another or overall twisting of the cellulose chains.

A Discrete Dichloride Tetrahydrate Trapped by a Cyclopropenium Cation: Structure and Spectroscopic Properties.

A discrete dichloride tetrahydrate cluster, [Cl2 (H2 O)4 ]2- , was obtained as a salt of the bis(diphenylamino)diethylamino cyclopropenium cation [C3 (NPh2 )2 (NEt2 )]+ and characterized by single-crystal X-ray diffraction and infrared spectroscopy. This chloride-chloride ion-pair cluster consists of a [Cl2 (H2 O)2 ]2- square with opposite edges bridged by water molecules to give a chair-like structure of the non-hydrogen atoms. The solid-state structure is essentially the same as the calculated gas-phase structure. Infrared spectra were also collected on the deuterium analogue [Cl2 (D2 O)4 ]2- . Computational studies were carried out on gas-phase [Cl2 (H2 O)4 ]2- to confirm the infrared band assignments in the solid state. The structure and infrared spectrum are consistent with the discrete nature of the cluster.

Ab Initio Calculation of Total X-ray Scattering from Molecules.

We present a method to calculate total X-ray scattering cross sections directly from ab initio electronic wave functions in atoms and molecules. The approach can be used in conjunction with multiconfigurational wave functions and exploits analytical integrals of Gaussian-type functions over the scattering operator, which leads to accurate and efficient calculations. The results are validated by comparison to experimental results and previous theory for the molecules H2 and CO2. Importantly, we find that the inelastic component of the total scattering varies strongly with molecular geometry. The method is appropriate for use in conjunction with quantum molecular dynamics simulations for the analysis of new ultrafast X-ray scattering experiments and to interpret accurate gas-phase scattering experiments.

Predicting the Outcome of Photocyclisation Reactions: A Joint Experimental and Computational Investigation.

Photochemical oxidative cyclodehydrogenation reactions are a versatile class of aromatic ring-forming reactions. They are tolerant to functional group substitution and heteroatom inclusion, so can be used to form a diverse range of extended polyaromatic systems by fusing existing ring substituents. However, despite their undoubted synthetic utility, there are no existing models-computational or heuristic-that predict the outcome of photocyclisation reactions across all possible classes of reactants. This can be traced back to the fact that "negative" results are rarely published in the synthetic literature and the lack of a general conceptual framework for understanding how photoexcitation affects reactivity. In this work, we address both of these issues. We present experimental data for a series of aromatically substituted pyrroles and indoles, and show that quantifying induced atomic forces upon photoexcitation provides a powerful predictive model for determining whether a given reactant will photoplanarise and hence proceed to photocyclised product under appropriate reaction conditions. The propensity of a molecule to photoplanarise is related to localised changes in charge distribution around the putative forming ring upon photoexcitation. This is promoted by asymmetry in molecular structures and/or charge distributions, inclusion of heteroatoms and ethylene bridging and well-separated or isolated photocyclisation sites.

Comparing the accuracy of perturbative and variational calculations for predicting fundamental vibrational frequencies of dihalomethanes.

Three dihalogenated methane derivatives (CH2F2, CH2FCl, and CH2Cl2) were used as model systems to compare and assess the accuracy of two different approaches for predicting observed fundamental frequencies: canonical operator Van Vleck vibrational perturbation theory (CVPT) and vibrational configuration interaction (VCI). For convenience and consistency, both methods employ the Watson Hamiltonian in rectilinear normal coordinates, expanding the potential energy surface (PES) as a Taylor series about equilibrium and constructing the wavefunction from a harmonic oscillator product basis. At the highest levels of theory considered here, fourth-order CVPT and VCI in a harmonic oscillator basis with up to 10 quanta of vibrational excitation in conjunction with a 4-mode representation sextic force field (SFF-4MR) computed at MP2/cc-pVTZ with replacement CCSD(T)/aug-cc-pVQZ harmonic force constants, the agreement between computed fundamentals is closer to 0.3 cm-1 on average, with a maximum difference of 1.7 cm-1. The major remaining accuracy-limiting factors are the accuracy of the underlying electronic structure model, followed by the incompleteness of the PES expansion. Nonetheless, computed and experimental fundamentals agree to within 5 cm-1, with an average difference of 2 cm-1, confirming the utility and accuracy of both theoretical models. One exception to this rule is the formally IR-inactive but weakly allowed through Coriolis-coupling H-C-H out-of-plane twisting mode of dichloromethane, whose spectrum we therefore revisit and reassign. We also investigate convergence with respect to order of CVPT, VCI excitation level, and order of PES expansion, concluding that premature truncation substantially decreases accuracy, although VCI(6)/SFF-4MR results are still of acceptable accuracy, and some error cancellation is observed with CVPT2 using a quartic force field.