Toward Universal Substituent Constants: Relating QTAIM Functional Group Descriptors to Substituent Effect Proxies.

Substituents modulate reactions, but their effects are commonly described by using proxies to their functional group properties. Substituent descriptors from the quantum theory of atoms in molecules, which are true functional group properties, are related here to these proxies, which have historically had chemically relevant meaning. Due to the large number of descriptors, multivariate analysis is used to intuit their significance. Multiple linear regression, principal component, and partial least squares regression analyses highlight that these substituent descriptors contain similar information to the proxies while being intrinsic, predictable substituent properties. Sources of error limiting quantitative reproduction of the proxy data include transferability, experimental accuracy, and solvation issues.

Toward universal substituent constants: Transferability of group descriptors from the quantum theory of atoms in molecules.

Traditionally, substituents are described not by their intrinsic properties, but by their effect elsewhere in a molecule. However, the quantum theory of atoms in molecules (QTAIM) provides a route to intrinsic substituent descriptors. Ideally, these descriptors would exhibit minimal change as the local environment changes, and hence be considered transferable. Whether this is true is an open question. Here, we evaluated the transferability of QTAIM functional group descriptors for 117 functional groups in a series of 17 substrates to determine whether descriptors obtained using hydrogen as substrate are transferable. The functional group volume has a strong, consistent, linear relationship throughout. All other hydrogen-based group descriptors exhibit a relatively strong linear relationship with those in carbon-based substrates and a reasonable linear relationship with those in non-carbon-based substrates. Outliers are readily interpretable in terms of substrate induced functional group geometry changes. As expected, directional descriptors lying along the substituent-substrate axis are the least conserved.

Silicon Forms a Rich Diversity of Aliphatic Polyol Complexes in Aqueous Solution.

A detailed examination of aqueous Si complexation by alditols and aldonic acids was conducted using high-sensitivity 29Si NMR spectroscopy of isotopically enriched solutions combined with theoretical modeling. Contrary to previous thinking, we have established that aliphatic polyols do not require a threo pair of hydroxy groups to form hypercoordinated Si complexes, although formation constants may be orders of magnitude higher if they are present. Thirteen distinctly different molecular assemblages containing 4-, 5-, or 6-coordinate Si centers have been identified, with significant concentrations of 5-coordinate Si bis-ligand complex being detected even under biologically relevant solution conditions.

Toward universal substituent constants: Model chemistry sensitivity of descriptors from the quantum theory of atoms in molecules.

The quantum theory of atoms in molecules (QTAIM) provides a theoretical foundation to determine the properties of functional groups through additive atomic contributions. Many studies have used QTAIM in their analyses with a variety of electronic structure methods, but it is unknown if the properties measured using one model chemistry, the combination of the electronic structure method and basis set, can be compared to those measured by another. Here, we evaluate the sensitivity of QTAIM functional group and bond critical point properties using six functionals and seven basis sets. High-level B2PLYPD3-BJ/aug-cc-pV5Z reference values are provided for 116 functional groups and the property sensitivity with respect to these values are evaluated based on absolute deviations and by assessing linear relationships. Functional group properties, including charges, dipoles, quadrupoles and volumes, were found to be mostly insensitive to choice of computational model chemistry. However, due to structural and topological inconsistencies, the 6-31G(d) basis set is not recommended for use. Bond critical point properties varied with choice of model chemistry, but models incorporating hybrid functionals and triple-ζ basis sets provided values suitable for use in regression studies.

Isothiirane: A Molecular Structure Dilemma Resolved.

The electronic structure of molecules is routinely assessed using a number of methodologies including Bader's Quantum Theory of Atoms in Molecules (QTAIM) and Weinhold's Natural Bond Orbital/Natural Resonance Theory (NBO/NRT). Previously these methods were applied to the study of isothiirane; however, the results obtained were incongruous with one another: the QTAIM analysis suggested an acyclic structure while NRT indicated a cyclic structure. The previous results assume the NRT description to be correct despite limitations in the analysis, while Foroutan-Nejad et al. (Chem. Eur. J. 2014, 20, 10140) employed a multiple molecular graph analysis to resolve the QTAIM discrepancy. In this work, we re-examine the electronic structure of isothiirane, employing a detailed NRT analysis and the catastrophe theory model originally described by Bader for the study of three-membered ring systems; additional analysis is performed using NMR tensor calculations and studying substituent effects. A congruous description of the electronic structure of isothiirane and the substituted versions is achieved using all modes of analysis. These results highlight how the careful application of commonly used methodologies can achieve a unified description of electronic structure. © 2018 Wiley Periodicals, Inc.

Identification of a mammalian silicon transporter.

Silicon (Si) has long been known to play a major physiological and structural role in certain organisms, including diatoms, sponges, and many higher plants, leading to the recent identification of multiple proteins responsible for Si transport in a range of algal and plant species. In mammals, despite several convincing studies suggesting that silicon is an important factor in bone development and connective tissue health, there is a critical lack of understanding about the biochemical pathways that enable Si homeostasis. Here we report the identification of a mammalian efflux Si transporter, namely Slc34a2 (also termed NaPiIIb), a known sodium-phosphate cotransporter, which was upregulated in rat kidney following chronic dietary Si deprivation. Normal rat renal epithelium demonstrated punctate expression of Slc34a2, and when the protein was heterologously expressed in Xenopus laevis oocytes, Si efflux activity (i.e., movement of Si out of cells) was induced and was quantitatively similar to that induced by the known plant Si transporter OsLsi2 in the same expression system. Interestingly, Si efflux appeared saturable over time, but it did not vary as a function of extracellular [Formula: see text] or Na+ concentration, suggesting that Slc34a2 harbors a functionally independent transport site for Si operating in the reverse direction to the site for phosphate. Indeed, in rats with dietary Si depletion-induced upregulation of transporter expression, there was increased urinary phosphate excretion. This is the first evidence of an active Si transport protein in mammals and points towards an important role for Si in vertebrates and explains interactions between dietary phosphate and silicon.

Inductive effect: a quantum theory of atoms in molecules perspective.

Substituent effects are ubiquitous in chemistry and the most fundamental is the inductive effect. In this study, the so-called inductive effect was probed in derivatives of bicyclo[1.1.1]pentane-1-carboxylic acid using the isodesmic reaction energy of the acid-base deprotonation, calculated at the PBE0/6-31++G(d,p) level of theory (used throughout). Although structure, molecular orbitals, and nuclear magnetic shielding parameters are discussed, the main focus of this study is the use of the quantum theory of atoms in molecules to analyze the electron density distribution. It was observed that the effect propagates via the manipulation of atomic dipole moments controlled by that of the substituent. As the dipole moment conforms to the principle of atomic transferability, it is found that the substituent dipole determined in simple systems (e.g., R-H) can be used to describe the effect upon the bicyclo[1.1.1]pentane-1-carboxylic acid system.

Characterizing nitrilimines with nuclear magnetic resonance spectroscopy. A theoretical study.

The 13C chemical shifts in selected nitrilimines, nitriles, acetylenes, allenes, and singlet carbenes have been calculated using density-functional theory [PBE0/6-311++G(2df,pd)] and the gauge including atomic orbital (GIAO) method. The effects of substitution on the 13C chemical shifts in nitrilimines, R1-CNN-R2, have been examined. The carbon nucleus is generally found to be deshielded by substituents in the order CH3 < NH2 < OH < F. Comparison with nitriles, acetylenes, and allenes shows that this effect is related to the presence of the cumulated functionality, C=N=N. Terminal N-substitution is found to have a larger effect than C-substitution due to a large increase in chemical shielding anisotropy. The electronic structure of nitrilimines has recently been shown to possess a carbene component whose resonance contribution varies widely with substitution, and, as previously reported, insight into the electronic structure can be gained by an analysis of the shielding tensor, especially for carbenes. Accordingly, the components of the diagonalized 13C shielding tensor for nitrilimines and stable singlet carbenes have been examined. This analysis suggests that diaminonitrilimine, H2N-CNN-NH2, may be a stable carbene, and, to the best of our knowledge, it would be the first acyclic, unsaturated stable carbene ever reported. Finally, a detailed analysis of the 13C chemical shifts shows that an increase in the dipolar character of nitrilimines induces a shielding at the carbon nucleus, while an increase in allenic or carbenic character tends to cause a deshielding.

The electronic structure of nitrilimines revisited.

A combination of density-functional theory and natural resonance theory has been used to show that a complete description of the electronic structure of nitrilimines, R(1)CNNR(2), requires four resonance structures (propargylic, allenic, 1,3-dipolar and carbenic); appropriate substituents were shown to enhance the carbene character of nitrilimines to the point where they may be considered stable carbenes.

Density functional study of lithium hexamethyldisilazide (LiHMDS) complexes: effects of solvation and aggregation.

The title compound, lithium hexamethyldisilazide (LiHMDS), has been studied using modern quantum-chemical methods in the form of the B3LYP approach. Monomers, dimers, trimers, and tetramers, microsolvated with up to four THF molecules have been considered. The choice of model complex is seen to be important-for instance, the simpler water molecule is shown to be an inappropriate substitute for the THF solvent. Calculated lithium NMR shieldings are reported, but by themselves, they seem to be insufficient for unequivocal assignments of the different species. The energetics of aggregation and solvation have been studied. Temperature effects are seen to be important, and the degrees of solvation and aggregation are higher at 0 K than at 298 K. The highest degree of THF solvation for the monomer and dimer is found to be three (0 K) and two (298 K), respectively. The highest possible degree of aggregation for unsolvated LiHMDS is four. However, in nonpolar solvents, formation of the LiHDMS dimer from the trimer is thermodynamically preferred. The pathway is likely to involve an intermediate tetramer. In THF solution, di-solvated monomers and dimers are the most likely species.

NMR quantum computing: applying theoretical methods to designing enhanced systems.

Density functional theory results for chemical shifts and spin-spin coupling constants are presented for compounds currently used in NMR quantum computing experiments. Specific design criteria were examined and numerical guidelines were assessed. Using a field strength of 7.0 T, protons require a coupling constant of 4 Hz with a chemical shift separation of 0.3 ppm, whereas carbon needs a coupling constant of 25 Hz for a chemical shift difference of 10 ppm, based on the minimal coupling approximation. Using these guidelines, it was determined that 2,3-dibromothiophene is limited to only two qubits; the three qubit system bromotrifluoroethene could be expanded to five qubits and the three qubit system 2,3-dibromopropanoic acid could also be used as a six qubit system. An examination of substituent effects showed that judiciously choosing specific groups could increase the number of available qubits by removing rotational degeneracies in addition to introducing specific conformational preferences that could increase (or decrease) the magnitude of the couplings. The introduction of one site of unsaturation can lead to a marked improvement in spectroscopic properties, even increasing the number of active nuclei.

Lowest singlet and triplet potential energy surfaces of S2N2.

Forty four stationary points have been located on the lowest singlet and triplet potential energy surfaces of S(2)N(2). Ten minima and ten saddle points on the lowest singlet surface and eleven minima and thirteen saddle points on the lowest triplet surface were found. All saddle points were connected to minima or lower-order saddle points by following the intrinsic reaction coordinate. Renner-Teller effects in the linear isomers were studied by examining their bending curves. The S(2)N(2) polymerization mechanism was investigated by first locating the transition state corresponding to ring opening and then considering all species connected to it that are close in energy. The commonly accepted mechanism is problematic due to the number of species that would lead to dissociation to SN + SN. Other possible isomers that are consistent with the experimental evidence but do not connect to SN radicals in the dissociation limit were examined. A mechanism of polymerization to (SN)(x)() is proposed that involves excitation of the square planar singlet molecule to the triplet surface. The triplet species then undergoes a puckering, and polymerization occurs in a direction approximately perpendicular to the S(2)N(2) plane. Consideration of the predicted vibrational frequencies suggests the structure of the second isomer of S(2)N(2). This isomer has a trans-NSSN structure with a long SS bond. The energetics of trans-NSSN are consistent with the observed temperature effects in the dimerization of SN. Analysis of the bending curves of linear NSSN and NSNS indicates that trans-NSSN is the only isomer which has a small yet significant barrier to that dimerization.