Analysis of numerous crystal structures from the Cambridge Structural Database (CSD) suggests bonding interactions between group 4 metal atoms and Lewis bases. DFT calculations consider the bond between the central group 4 metal atom of MX2Y2 (M = Ti, Zr, Hf; X = F, Cl, Br, I; Y = N = C(CH3)2) and Lewis base NH3. Strong interactions, bordering on covalency, are observed in all cases that rely in part on the σ-hole on the M atom. Interaction energies lie between 25 and 30 kcal/mol. The bond grows stronger as M or X is enlarged, but this growth is gradual. Because of the larger deformation energies required for the Ti Lewis acid to adjust its structure to the incoming nucleophile, the binding energies follow the order Ti < Zr < Hf and occupy the range between 15 and 21 kcal/mol. The bonding of Ti is dominated by electrostatics, but it is polarization that plays the larger role for Hf.

When bonded to electropositive Li, the methyl C exhibits strong Lewis basicity. DFT calculations show a highly negative electrostatic potential on the C and a HOMO that closely resembles a C lone electron pair. LiMe and some of its oligomers are paired in the context of both halogen and hydrogen bonds with dihalogens and HX (X = F, I, Br, Cl). There is a wide variation of halogen bond strength from 1 to 20 kcal/mol, while the H-bonds cover a narrower range between 4 and 10 kcal/mol. The electrostatic potential minimum and the binding of (LiMe)2 are weakened relative to its monomer. Electrostatic effects account for slightly less than half of the total attractive energy in the halogen bonds and just over half for the H-bonds. Enlarging the cluster to four and six Li atoms has a very mild weakening effect on the binding, reaching its asymptote for some 6-8 Li.

A quantum chemical study of the interactions between N-methylacetamide (NMA), which serves as a peptide model, and poloxamer building blocks made up of polyethylene oxide (PEO) and polypropylene oxide (PPO) dimers shows a range of noncovalent interactions. Eight stable NMA···PEO complexes were found, with interaction energies between 2.24 and 6.73 kcal/mol. NMA···PPO complexes show slightly stronger interactions, reaching up to 7.39 kcal/mol. Besides NH···O and CH···O hydrogen bonding, several complexes also exhibit notable nonclassical C═O···O interactions. These are stabilized by bidirectional charge transfer (CT) that includes C═O π → O-C σ* and O(lp) → C═O π* donations. Such interactions improve binding strengths to levels similar to those of typical hydrogen bonds. The findings highlight that hydrogen bonding and CT work together in peptide-poloxamer interactions.

MgMe2 can act in a dual capacity, as an electron donor through a methyl group, or as an acceptor via Mg. HOX is also capable of both functions, accepting density at its H and halogen X termini, or donation via the central O. Bonding between these two molecules can therefore encompass either hydrogen, halogen, or Mg-bonds, named according to the identity of the electron acceptor atom. Quantum chemical calculations are used to assess the strengths and other properties of these bonding motifs, which show the MgBs to be strongest, some exceeding 50 kJ/mol, followed by HBs and then by XBs, where the latter is highly influenced by the identity of X. The presence of a MgB enhances the strengths of the others, adding as much as 13 kJ/mol to the total binding energy. In contrast, the HB and XB exert an anticooperative effect on one another. The synergy between the MgB and the other two bonds can be used to build highly stable extended systems, with applications to the design of supramolecular structures.

The effects of stacking an aromatic ring over another that bears a halogen atom is considered via quantum chemical calculations. Benzene, furan, cytosine, and phenol slightly weaken the CI···N halogen bond between iodobenzene and NH3, while strengthening is associated with dinitrobenzene, pyrimidine, thymine, and imidazole. A more substantial halogen bond magnification occurs when the external ring is rotated so as to donate a proton in forming a H-bond with the π system of iodobenzene in a T-shaped complex. In most cases, this external ring acts as a sink for some of the electron density donated to iodobenzene by the NH3 nucleophile.

The directionality of bonds is an important feature for many compounds relevant in biochemistry, crystal engineering and materials chemistry. It is widely accepted that a good number of contacts between ions (including ionic bonds) are nondirectional. A CSD survey is employed to demonstrate that significant directionality of cation & ctdot;anion interactions is observed for systems which include a chalconium cation. Nearly 70% of all found structures contain a R-Y & ctdot;LB angle (Y = S, Se, Te; LB = atom from anionic Lewis base) within 10 degrees of linearity. Such structural motifs are commonly termed charge-assisted chalcogen bonds. Quantum chemical analysis traces this angular tendency to a compromise between coulombic forces and exchange repulsion, which pull in opposite directions. Charge transfer, polarization, and dispersion terms are much smaller in magnitude and thus exert a lesser influence.

Carbone compounds are characterized by a zero oxidation state on divalent C, which contains two lone pairs, coupled with dative bonding to its two substituents. The ability of this carbone center to act as an electron donor is examined by pairing it with 29 different halogen-containing Lewis acids. DFT calculations show the binding to be quite strong, eclipsing that of a NH3 Lewis base, despite the similarity of their electrostatic potentials. Binding energies span a wide range from nearly zero up to more than 40 kcal mol(-1); interaction energies are even larger. The more weakly bound dyads, with binding energies below 20 kcal mol(-1), have all the characteristics of conventional halogen bonds, including an increase in binding energy in the usual Cl < Br < I sequence. For the more powerful Lewis acids, there is a progressively larger degree of displacement of the halogen atom from the Lewis acid to the carbone center, some essentially fully transferred. The dependence of the energetics on the halogen atom reverses for these complexes: Cl > Br > I.

DFT calculations have been used to analyze the osme bonds pairing MO4 and MO3Me (M = Fe, Ru, Os) with a methyl group of BeMe2 and MgMe2. Despite lacking a formal lone pair, the methyl C atom can act as a directional and tunable electron donor. Interaction energies span the range between -7 and -23 kJ mol-1, with Fe forming the weakest and Os the strongest bonds. The replacement of one O atom of MO4 by a methyl group substantially strengthens the interaction even though it attenuates the σ-hole on M. The osme bonds are dominated by electrostatic and dispersion energies in varying amounts, but polarization plays a particularly important role for the MO3Me systems, especially for M = Fe.

Chalcogen (Y) atoms in bivalent coordination are known to contain two separate σ-holes and so are thought to be capable of two chalcogen bonds (ChBs) to a pair of nucleophiles. However, the two σ-holes of the bivalent Y atoms within an aromatic ring coalesce so as to form an extended positive region. These molecules are thus able to engage in trifurcated ChBs to three separate nucleophiles, one directly between the two formal σ-holes. This sort of bonding is aided by the character of the low-lying vacant orbitals that are well situated to accept charge from three nucleophilic atoms in these positions. This principle is applied to design a series of receptors where three nucleophilic N atoms are located on a single molecule. The optimal receptor contains three amine groups separated by flexible ethyl groups. The interaction energy of this receptor with S, Se, and Te chalcogenadiazoles is computed to be 9.7, 13.9, and 20.5 kcal/mol, respectively. Consideration of binding, rather than pure interaction energy, would shift the designation of the optimal receptor to those with a more rigid pyridine core. Immersion of these complexes in water reduces these quantities somewhat but still leaves them in the 5-16 kcal/mol range.

A halogen bond is formed by a wide range of divalent CR2 carbenes with ICN as the Lewis acid, and the results are examined via DFT calculations. These carbenes form much stronger halogen bonds than more common Lewis bases such as NH3 and OH2. The binding occurs through the carbene C lone pair and is enhanced if the central C is covalently attached to C on the R substituent, as compared to O or N. Interaction energies are as high as 30 kcal mol-1, and the C⋯I bond contains a certain degree of covalent character. The two lone pairs on the C atom of the carbene, when connected through dative bonds to units such as NH3 and OH2, make this C especially strongly nucleophilic, enough so as to partially extract the I from the ICN unit. The carbene halogen bonds have all of the characteristics of their classic counterparts, including a high dependence upon Coulombic interaction.

The bonding between the metal atom of M(CO)3 and the aromatic ring of benzene and halobenzene is examined by DFT calculations. Metals are drawn from the 3d and 4d periods of groups 6-12. The bonding mode is quite variable in strength, geometry, and fundamental nature: metals from the left side of the periodic table tend to form strong bonds, bordering on coordinate covalent, and can induce nonplanar distortions into the benzene ring, while the M atoms further to the right engage in weaker noncovalent bonds. Halogenation of the benzene ring causes only minor perturbations to this M··π bonding. The transfer of charge away from the ring to the metal species facilitates a deepening of the σ-hole on the halogen atom of the ring and a strengthening of its halogen bond to NH3. This cooperativity is not large, amounting to less than 1.5 kcal/mol.

Depending upon the level of halogenation, the electrostatic potential of the π region above the molecular plane of an alkene can vary over a wide range and can be either positive or negative. The ability of H2CCHX, H2CCFX, and F2CCFX, where X=F, Cl, Br, I, to interact with either a nucleophile or electrophile, is studied by DFT calculations. This binding is compared with the σ-hole CX···N halogen bonding with NH3. The negative potential above H2CCHX facilitates ClH···π H-bonding with HCl, while NH3 can bind to the positive π-hole above F2CCFX; the partially halogenated H2CCFX is able to act as both nucleophile and electrophile. The introduction of a σ-hole XB acts to generally weaken the CC bond of H2CCHX, but the effect is less unambiguous for the more highly halogenated alkenes. These effects are reversed upon the formation of a π-tetrel bond with NH3. The largest perturbations are associated with the π-HB, which causes a sizable CC bond weakening. Combination of two sorts of intermolecular bonds is cooperative when the central alkene acts as both electron donor and acceptor and anticooperative when it acts as double acceptor.

Dictating cell growth and morphology, cellulose biosynthesis is intrinsic to plant cell biology. Accordingly, cellulose biosynthesis inhibitors (CBIs) are important herbicides, toxins, and experimental tools. We currently lack mechanistic understanding of CBI activity, preventing engineering of herbicide selectivity and disease immunity. Contrasting classical inhibitors, we unexpectedly identify the unusual Streptomyces phytotoxin thaxtomin A as the only in vitro -active CBI, with unprecedentedly broad-spectrum activity against various cellulose synthase enzymes. High-resolution cryo-electron microscopy reveals that thaxtomin A leverages exotic nitroaromatic chemistry to target a strictly conserved site in cellulose synthase's polysaccharide secretion channel. Strikingly, in vitro biosynthesis and biophysical assays demonstrate thaxtomin A's near-picomolar efficacy. Plant and algal systems reveal that its global arrest of cellulose biosynthesis produces an osmotically driven crisis in expanding cells. Finally, site-directed mutagenesis generates the first toxin-resistant cellulose synthase. Our results underscore cellulose's critical function in plant lifeforms and inform efforts to inhibit related enzymes across kingdoms.

The HOMO of Be(CO)3 resembles a Be lone pair that can donate charge in the context of a halogen bond. This propensity is tested via quantum chemical calculations wherein Be(CO)3 is paired with XF, XCl, XCN, and XCF3 (X = I, Br, Cl). In the case of the latter two molecules where X is attached to C, a fully noncovalent halogen bond is formed that varies in strength between 2.2 and 9.7 kcal/mol. The bonding causes a stretch of the internal X-C bond and a red shift of its stretching frequency. Interactions with XF and XCl are much stronger, 40 kcal/mol and higher, containing strong elements of covalency. The bridging X atom in these complexes shifts a good deal toward the Be center in what may be classified as partial transfer or halogen sharing. In contrast to the noncovalent halogen bonds involving XCN and XCF3, where the interaction is strengthened as X grows larger, the opposite trend is observed for the halogen-shared complexes including XF and XCl.

The effect of the replacement of the H-bonds (HBs) that hold nucleic acid base pairs together by halogen bonds (XBs) is examined by DFT calculations. When in its Hoogsteen configuration,...

Both the carbonyl and hydroxyl O atoms of the carboxyl group are capable of acting as electron donor in the context of noncovalent bonds. These two O atoms of acetic acid are each allowed to form an H-bond with HCl and a halogen bond with IF, and the interactions are monitored by quantum chemical calculations. The electrostatic potential on the carbonyl O is more negative than that on OH, and the HOMO is weighted toward the carbonyl. The interaction energies are consequently considerably stronger for the CO. A series of ligands are added to the carboxyl group that extract electron density from the carbonyl O and add density to OH. These arrangements enhance the interaction energies involving OH, some by nearly 50%. These same ligands have a lesser effect on bonds involving CO, many of which are actually strengthened, despite the reduced magnitude of its negative potential. Consequently, the CO remains the favored site for an electrophile, regardless of the ligands that might be present.

Crystal structures show F atoms of neighboring molecules sitting close to one another and are presumed to help stabilize the crystal via halogen bonds. The possibility of such F..F halogen bonds is tested via DFT calculations that consider first the actual crystal geometry, and then proceed to a more general set of systems without the constraints of the packing forces within the crystal. It is shown that these F..F contacts offer little if any in the way of stabilization, and should not be categorized as halogen bonds.

A halobenzene molecule contains several sites that are capable of acting in an electron‐donating capacity within a H‐bond. One set of such sites comprise the lone electron pairs of the halogen (X) atoms on the periphery of the ring. The π‐electron system above the ring plane can also fulfill this function in many cases. DFT calculations are applied to compare and contrast the propensity of these two site types to engage in such a H‐bond within the context of mono, di, tri, tetra, and hexasubstituted halobenzenes. The X atoms chosen for study comprise the full set: F, Cl, Br, and I. It is found that even when the electrostatic potential of the X lone pair is more negative than that above the ring, it is the latter position which is the preferred binding site of HCl in most cases. This preference switches over to the X lone pair only for higher order of substitution, with n=4 or 6. This pattern is explained in large measure by the higher contribution of dispersion when the proton donor is located above the ring.

Strong negative charge on the tetravalent apical C of propellane can attract an electrophile, which can then extract charge from the prominent lobe of its C–C bonding orbital, to form a strong noncovalent bond with C as an electron donor.

While it is usually agreed that a major component in the composition of a H-bond is the electrostatic attraction associated with a positive charge on the bridging H, there has recently arisen some question as to whether a true H-bond can exist when this atom bears a negative charge. Quantum chemical calculations address this question for a variety of potential proton donor molecules where the H atom is bonded to atoms covering a wide range of electronegativity, including the halogen, chalcogen, pnicogen and tetrel families, as well as metal atoms. These molecules are bound to Lewis bases by a variety of noncovalent bonds, including tetrel and halogen bonds, but H-bonds are rare, and exceedingly weak when the H atom does not carry a substantial positive charge.