Brain imaging signatures of neuropathic facial pain derived by artificial intelligence.

Advances in neuroimaging have permitted the non-invasive examination of the human brain in pain. However, a persisting challenge is in the objective differentiation of neuropathic facial pain subtypes, as diagnosis is based on patients' symptom descriptions. We use artificial intelligence (AI) models with neuroimaging data to distinguish subtypes of neuropathic facial pain and differentiate them from healthy controls. We conducted a retrospective analysis of diffusion tensor and T1-weighted imaging data using random forest and logistic regression AI models on 371 adults with trigeminal pain (265 classical trigeminal neuralgia (CTN), 106 trigeminal neuropathic pain (TNP)) and 108 healthy controls (HC). These models distinguished CTN from HC with up to 95% accuracy, and TNP from HC with up to 91% accuracy. Both classifiers identified gray and white matter-based predictive metrics (gray matter thickness, surface area, and volume; white matter diffusivity metrics) that significantly differed across groups. Classification of TNP and CTN did not show significant accuracy (51%) but highlighted two structures that differed between pain groups-the insula and orbitofrontal cortex. Our work demonstrates that AI models with brain imaging data alone can differentiate neuropathic facial pain subtypes from healthy data and identify regional structural indicates of pain.

Weak interactions as diagnostic tools for inductive effects.

No broadly applicable and well-defined measure for the inductive effects of substituents (outside of the context of substituted benzenes) exists. We assess the viability of two different forms of weak interactions as tools for this purpose. The responses of interatomic (I···N and Ge···N) separations in the halogen-bonded and dative covalent complexes F3CI···Y and FH3Ge···Y, where Y = NH2R, afford a direct ordering of a diverse set of substituents, R, according to their influence on the availability of the N lone pair in the base (NH2R) for bonding. Despite their structural and electronic differences, the two bonding modes that we consider show good qualitative agreement on the electron-withdrawing inductive tendencies of substituents because of their sensitivity to the electronic environment at the donor site (the N center, in this case) on the base. The choice of the monosubstituted (NH2R) base minimizes steric interactions, resonance, and other electronic effects that could interfere with the bonding between N and the I or Ge centers in the complexes. We find, moreover, that the inductive tendencies for substituents in these complexes are, in general, not additive. Depending on the identity of R, the trisubstituted base (NR3) may actually reverse rather than enhance changes in the acid-base interactions that are achieved going from NH3 to NH2R. These outcomes are observed at the MP2(full) and the M06-2X levels of theory, for both halogen and dative bonding interactions. A conservative ordering of substituents according to the observed inductive tendencies is presented.

Halogen bonding: unifying perspectives on organic and inorganic cases.

We find for distinct classes of halogen bonded complexes (MF3-X···Y) that the ab initio BSSE-corrected binding energies (ΔE) and enthalpies (ΔH) are predicted by functions of the form y = A/r(n) + C. Here X is a halogen atom, Y is a base, r is the X···Y separation, and A, n, and C are constants. The actual value of n (5.5 < n < 7.0 for ΔE) for each class is determined evidently by the availability of the lone pairs on the base and is insensitive to M such that all of the complexes of a given base fall on the same curve for y versus r. Remarkably, several bases show the same behavior in some cases such that just three curves account for 55 MF3I···Y complexes of 11 bases, where M = C, Si, Ge, Sn, and Pb. Two additional bases, THF and NF3, which form especially strong and weak complexes, respectively, are in classes by themselves. Anomalous modes of halogen bonding are identified; in particular, furan forms sigma-hole complexes via carbons 2 and 3 (through the π system) in the ring in preference to the oxygen site. These results are in line with experimental observations for furan-dihalogen complexes, and several other small MF3I···Y pairs are proposed in this work for experimental interrogation. Instead of halogen bonding, CF4 tends to form weak sigma-hole bonds to bases via the polarized central carbon atom, and new examples of such pro-dative interactions to carbon in CF4 are identified in this work. We find that GeF3I and SnF3I form I···Y halogen bonds of comparable energies to those formed by the smaller and better studied CF3I. PbF3I forms the strongest halogen bond regardless of the identity of the base; SiF3I consistently forms the weakest link.

The weak helps the strong: sigma-holes and the stability of MF(4)·base complexes.

Bonding interactions between an electron-deficient region (a sigma-hole) on M and electron donors in MF4-Base complexes, where M = C, Si, Ge, Sn, and Pb, are examined and rationalized. These interactions are seen to transition from weak primarily noncovalent interactions for all bases when M = C to stronger primarily covalent bonds in adducts as the valence shell expands for the heavier M atoms. For M = Ge, Sn, and Pb, the complexes are particularly stable. The consistent axial preference in these systems is anticipated by previous studies and is readily explained from the vantage point of sigma-hole interactions. A series of bound complexes of common bases such as pyridine, tetrahydrofuran, and water are identified, some of which are even more stable than the SiF4·NH3 and SiF4·N(CH3)3 complexes that have already been identified experimentally. Sigma-hole bonding to di- and poly-substituted central atoms, perhaps on par with halogen bonding, is expected to become increasingly important as an ordering interaction in materials science and engineering. Group 14 compounds have distinct advantages in this respect.

Plane and simple: planar tetracoordinate carbon centers in small molecules.

A class of neutral 18-electron molecules with planar tetracoordinate carbon (ptC) centers is introduced. We show computationally that when n = 3 the neutral singlet molecule C(BeH)(n)(BH(2))(4-n) and other isoelectronic (18-valence electron) molecules of main group elements collapse from locally tetrahedral arrangements at the C-center to (near) planar tetracoordinate structures. For C(BeH)(3)BH(2) and C(CH(3))(BH(2))Li(2), for example, the tetrahedral type conformation is not even a minimum on the potential energy surface at the B3PW91, MP2(full), or CCSD levels of theory. The Mg analogue C(MgH)(3)BH(2) of the Be system also features a completely flat global minimum (with even higher energy planar minima in both cases as well). Other neutral compounds that may prefer planar geometries are apparent, and new openings for experimental investigations and theoretical analyses of planar tetracoordinate main group systems are identified. The planar conformation persists at one center in the C(BeH)(3)BH(2) dimer, and may be identifiable in higher order clusters of ptC molecules as well.