Anions as Lewis Acids in Noncovalent Bonds.

The ability of an anion to serve as electron-accepting Lewis acid in a noncovalent bond is assessed via DFT calculations. NH3 is taken as the common base, and is paired with a host of ACln - anions, with central atom A=Ca, Sr, Mg, Te, Sb, Hg, Zn, Ag, Ga, Ti, Sn, I, and B. Each anion reacts through its σ or π-hole although the electrostatic potential of this hole is quite negative in most cases. Despite the contact between this negative hole and the negative region of the approaching nucleophile, the electrostatic component of the interaction energy of each bond is highly favorable, and accounts for more than half of the total attractive energy. The double negative charge of dianions precludes a stable complex with NH3.

Anti-Electrostatic Pi-Hole Bonding: How Covalency Conquers Coulombics.

Intermolecular bonding attraction at π-bonded centers is often described as "electrostatically driven" and given quasi-classical rationalization in terms of a "pi hole" depletion region in the electrostatic potential. However, we demonstrate here that such bonding attraction also occurs between closed-shell ions of like charge, thereby yielding locally stable complexes that sharply violate classical electrostatic expectations. Standard DFT and MP2 computational methods are employed to investigate complexation of simple pi-bonded diatomic anions (BO-, CN-) with simple atomic anions (H-, F-) or with one another. Such "anti-electrostatic" anion-anion attractions are shown to lead to robust metastable binding wells (ranging up to 20-30 kcal/mol at DFT level, or still deeper at dynamically correlated MP2 level) that are shielded by broad predissociation barriers (ranging up to 1.5 Å width) from long-range ionic dissociation. Like-charge attraction at pi-centers thereby provides additional evidence for the dominance of 3-center/4-electron (3c/4e) nD-π*AX interactions that are fully analogous to the nD-σ*AH interactions of H-bonding. Using standard keyword options of natural bond orbital (NBO) analysis, we demonstrate that both n-σ* (sigma hole) and n-π* (pi hole) interactions represent simple variants of the essential resonance-type donor-acceptor (Bürgi-Dunitz-type) attraction that apparently underlies all intermolecular association phenomena of chemical interest. We further demonstrate that "deletion" of such π*-based donor-acceptor interaction obliterates the characteristic Bürgi-Dunitz signatures of pi-hole interactions, thereby establishing the unique cause/effect relationship to short-range covalency ("charge transfer") rather than envisioned Coulombic properties of unperturbed monomers.

How Aromatic Fluorination Exchanges the Interaction Role of Pyridine with Carbonyl Compounds: The Formaldehyde Adduct.

The rotational spectrum of the weakly bound complex pentafluoropyridine⋅⋅⋅formaldehyde has been investigated using Fourier transform microwave spectroscopy. From the analysis of the rotational parameters of the parent species and of the 13 C and 15 N isotopologues, the structural arrangement of the adduct has been unambiguously established. The full ring fluorination of pyridine has a dramatic effect on its binding properties: It alters the electron density distribution at the π-cloud of pyridine creating a π-hole and changing its electron donor-acceptor capabilities. In the complex, formaldehyde lies above the aromatic ring with one of the oxygen lone pairs, as conventionally envisaged, pointing toward its centre. This lone pair⋅⋅⋅π-hole interaction, reinforced by a weak C-H⋅⋅⋅N interaction, indicates an exchange of the electron-acceptor roles of both molecules when compared to the pyridine⋅⋅⋅formaldehyde adduct. Tunnelling doublets due to the internal rotation of formaldehyde have also been observed and analysed leading to a discussion on the competition between lone pair⋅⋅⋅π-hole and π⋅⋅⋅π stacking interactions.

Anion⋠⋠⋠Anion Coinage Bonds: The Case of Tetrachloridoaurate.

Interactions in crystalline tetrachloridoaurates of acetylcholine and dimethylpropiothetine are characterized by Au⋅⋅⋅Cl and Au⋅⋅⋅O short contacts. The former interactions assemble the AuCl4 - units into supramolecular anionic polymers, while the latter interactions append the acetylcholine and propiothetine units to the polymer. The distorted octahedral geometry of the bonding pattern around the gold center is rationalized on the basis of the anisotropic distribution of the electron density, which enables gold to behave as an electrophile (π-hole coinage-bond donor). Computational studies prove that gold atoms in negatively charged species can function as acceptors of electron density. The attractive nature of the Au⋅⋅⋅Cl/O interactions described here complement the known aurophilic bonds involved in gold-centered interactions.

π-Hole Interactions Involving Nitro Aromatic Ligands in Protein Structures.

Studying noncanonical intermolecular interactions between a ligand and a protein constitutes an emerging research field. Identifying synthetically accessible molecular fragments that can engage in intermolecular interactions is a key objective in this area. Here, it is shown that so-called "π-hole interactions" are present between the nitro moiety in nitro aromatic ligands and lone pairs within protein structures (water and protein carbonyls and sulfurs). Ample structural evidence was found in a PDB analysis and computations reveal interaction energies of about -5 kcal mol-1 for ligand-protein π-hole interactions. Several examples are highlighted for which a π-hole interaction is implicated in the superior binding affinity or inhibition of a nitro aromatic ligand versus a similar non-nitro analogue. The discovery that π-hole interactions with nitro aromatics are significant within protein structures parallels the finding that halogen bonds are biologically relevant. This has implications for the interpretation of ligand-protein complexation phenomena, for example, involving the more than 50 approved drugs that contain a nitro aromatic moiety.

π-Hole Bonds: Boron and Aluminum Lewis Acid Centers.

MP2/aug-cc-pVTZ calculations were performed on complexes of boron and aluminum trihydrides and trihalides with hydrogen cyanide (ZH3 -NCH and ZX3 -NCH; Z=B, Al; X=F, Cl). The complexes are linked through the B⋅⋅⋅N and Al⋅⋅⋅N interactions, which are named as triel bonds and which are classified as π-hole bonds. It was found that they possess numerous characteristics of typical covalent bonds, since they are ruled mainly by processes of the electron charge shift from the Lewis base to the Lewis acid unit. Other configurations of the ZH3 -NCH and ZX3 -NCH complexes linked by the dihydrogen, hydrogen, and halogen bonds were found. However, these interactions are much weaker than the corresponding π-hole bonds. The quantum theory of atoms in molecules and the natural bond orbital approaches were applied to characterize the complexes and interactions analyzed. The crystal structures of triel trihydrides and triel trihalides were also analyzed for comparison with the results of calculations.