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DFT calculations consider the interactions between linear MR 2 and a series of N-bases, where M is Hg or Zn and its R substituents are CCH, CN, or NO 2 . NCH, NH 3 , and NMe 3 were considered as three different N-bases. Zn forms stronger bonds with the N bases than does Hg, and they strengthen along with the electron-withdrawing power of the R substituent, varying over a wide range from 3.4 to 43.9 kcal/mol. Another factor contributing to the bond strength is the nucleophilicity of the base: NCH < NH 3 < NMe 3 . All MR 2 Lewis acids can bind at least two bases, which are situated along the R-M-R bisecting plane, fairly close to one another, with θ(N-M-N) angles between 67° and 117°. The presence of a more electron-withdrawing substituent R and more powerful nucleophile allows up to 4 bases to bind to M. The properties of these bonds place them along a continuum, some clearly noncovalent, while other contain a good deal of covalent character.

A systematic theoretical study was conducted on the triel bonds (TrBs) within the TrX 3 ···Be(CO) 3 complexes (Tr = B, Al, Ga, In, Tl; X = H, F, Cl, Br, I). The interaction energies of these systems range between 4 and 38 kcal/mol. The TrB weakens as X becomes more electronegative in the B and Al systems, while the opposite pattern of stronger bonds is observed in the In and Tl analogues. The dominant component of the TrB is polarization energy, which arises from charge transfer from Be(CO) 3 to TrX 3 . The source of the density is a confluence of CO π-bonding orbitals at the Be center that resembles a Be lone pair, and which makes the molecular electrostatic potential above the Be somewhat negative. This π-lump is paired with the highly positive π-hole above the Tr, and a large amount of charge is transferred to the empty p z orbital of Tr. These factors, when considered in conjunction with large AIM measures, confer on this TrB a certain degree of covalency.

The effects of deviations from nonlinearity around the carbonyl proton acceptor of an amide group are assessed by DFT quantum chemical calculations for both CH··O and NH··O H-bonds. The proton donors are the imidazole functional group of His and the indole of Trp, which are paired respectively with N -methylacetamide and acetamide. The displacement of either CH or NH group toward the carbonyl O sp 2 lone pairs stabilizes the system and strengthens the H-bond. But the two donor groups differ in their response to a shift out of the amide plane. While the NH··O H-bond is weakened by this displacement, a substantial strengthening is observed when the CH donor is moved out of this plane, in one direction versus the other. This pattern is explained on the basis of simple Coulombic considerations.

It is usually assumed that the maximal noncovalent bond strength is achieved by full geometry optimization of the geometry of the dyad. Density functional theory calculations show this not to be the case. A number of systems are considered that include osme, tetrel, pnictogen, and chalcogen bonds, involving both σ- and π-holes, as well as hypervalency. By suitable adjustment of the bond angles within the Lewis acid, the base can be drawn closer than in the optimized structure, with an accompanying substantial strengthening of the noncovalent bond, by more than 10 kcal/mol in some cases. The energetic cost of this deformation from the optimized geometry can be surprisingly small in comparison to the gain in the interaction energy. Taking the opposite approach of first pushing the two subunits closer to one another and then permitting internal geometries to adjust to the shortened distance produces only minimal bond strengthening.

The three Z-X covalent bonds of a ZX 3 unit (Z = P, As, Sb, Bi) are normally arranged in a pyramidal structure. Quantum chemical calculations show that pnicogen bonds (ZBs) to the central Z are weakened if ZX 3 is flattened, as in the opening of an umbrella. The partial closing of the umbrella has the opposite effect of substantially strengthening these ZBs, even amounting to a 2- or 3-fold magnification in certain cases. The strongest such bonds, wherein Sb and Bi are in a strained configuration within a ZO 3 CH model system, have interaction energies of 20 kcal/mol with an NH 3 base. Most of these systems, whether flattened or more pyramidal, are capable of engaging in three ZBs simultaneously, despite a certain amount of negative cooperativity.

The properties of the bond between a N-ligand and a Lewis acid containing a σ-hole are studied by quantum chemical methods. Interactions considered include pnicogen bonds involving SbX 5 , PX 5 , and PX 3 , where X represents any of the halogen atoms F, Cl, Br, or I. Also studied are the tetrel bonds of PbX 4 and SiX 4 , as well as the chalcogen bond involving TeOX 4 . Both NH 3 and NCH are applied as two possible bases of differing potency. Some of the bonds are very strong with interaction energies easily exceeding 25 kcal/mol and with AIM bond critical point densities much higher than 0.04 au, suggesting their classification as coordinate covalent bonds. The pentavalent SbX 5 and PX 5 fall into this category when combined with NH 3 , as does TeOX 4 . Although the tetrel bonds involving PbX 4 are only slightly weaker, they are probably better viewed as a strong noncovalent bond on the cusp of covalency. Changing the internal bonding of hypervalent SbX 5 to the more conventional SbX 3 weakens the interaction to a classical noncovalent pnicogen bond. Reducing the base nucleophilicity from NH 3 to NCH weakens the bonds so that they are clearly noncovalent.

While a good deal of information has accumulated concerning the manner in which an intramolecular noncovalent bond can affect the relative energies of various conformers, less is known about how such bonds might affect the dynamics of interconversion between them. A series of molecules are constructed in which symmetrically equivalent conformers containing a noncovalent bond can be interconverted by a bond rotation, the energy barrier to which is computed by quantum chemical methods. The rotation of a CF 3 group attached to a phenyl ring is speeded up if a Se··F chalcogen bond can be formed with a SeH or SeF group placed in an ortho position, a bond that is present in and stabilizes the rotational transition state. The analogous SnF 3 group can, on the other hand, engage in a Sn··Se tetrel bond in its global minimum. The energetic cost of breakage of this bond is not fully compensated by the appearance of a Se··F chalcogen bond in the rotational transition state. Other systems were designed by placing two phenyl rings on opposite ends of an octahedrally disposed SeF 4 group. A high barrier inhibits their rotation with bulky Br atoms in ortho positions, but this barrier is lowered if Br is replaced by groups that can engage in either chalcogen (SeH or SeF) or pnicogen (AsH 2 ) bonds with the F atoms in the rotational transition state. The barrier reduction is closely related to the strength of these noncovalent bonds.

The imidazolium cation has a number of different sites that can interact with a nucleophile. Adding a halogen atom (X) or a chalcogen (YH) group introduces the possibility of an NX···nuc halogen or NY···nuc chalcogen bond, which competes against the various H-bonds (NH and CH donors) as well as the lone pair···π interaction wherein the nucleophile lies above the plane of the cation. Substituted imidazoliums are paired with the NH 3 base, and the various different complexes are evaluated by density functional theory (DFT) calculations. The strength of XB and YB increases quickly along with the size and polarizability of the X/Y atom, and this sort of bond is the strongest for the heavier Br, I, Se, and Te atoms, followed by the NH···N H-bond, but this order reverses for Cl and S. The various CH···N H-bonds are comparable to one another and to the lone pair···π bond, all with interaction energies of 10-13 kcal/mol, values which show very little dependence upon the substituent placed on the imidazolium.

The heavy atom effect is a widely utilized strategy to enhance the phosphorescence intensity of organic molecules. Among the preferred choices, heavy halogen atoms such as bromine (Br) or iodine (I) have gained popularity. However, the incorporation of these heavy atoms can introduce challenges due to the presence of unstable excited states that undergo dissociation upon excitation. This study focuses on investigating the excited states of the C 6 H 5 I molecule, with particular emphasis on the intricate interplay of spin-orbital coupling effects, employing multireference ab initio methodologies. The absence of phosphorescence in the C 6 H 5 I molecule is attributed to the efficient energy transfer to dissociative excited states and the near-zero spin-orbital coupling between stable triplet sub-levels and the ground singlet state. To gain insights into the explicit dynamics of the excited states, the research employed Ehrenfest dynamics driven by real-time time-dependent density functional theory (TDDFT). Furthermore, the study explored the complete active space compositions and various post-CASSCF (complete active space self-consistent field) approaches.

Quantum calculations study the potential of an intramolecular H-bond between the halogen atom (X) of a halobenzene and a substituent placed ortho to it, to amplify the ability of X to engage in a halogen bond (XB) with a Lewis base. H-bonding substituents NH 2 , CH 2 CH 2 OH, CH 2 OH, OH, and COOH were added to halobenzenes (X = Cl, Br, I). The amino group had little effect, but those containing OH increased the CX···N XB energy to a NH 3 nucleophile by about 0.5 kcal/mol; the increment associated with COOH is larger, nearly 2 kcal/mol. These energy increments were approximately doubled if two such H-bonding substituents are present. Combining a pair of ortho COOH groups with an electron-withdrawing NO 2 group in the para position has a particularly large effect, raising the XB energy by about 4 kcal/mol, which can amount to as much as a 4-fold magnification.

Quantum calculations study the manner in which the involvement of a halogen atom as a proton acceptor in one or more H bonds (HBs) affects the strength of the halogen bond (XB) it can form with a nucleophile aligned with the X σ-hole. A variety of Lewis acids wherein X = F, Cl, Br, and I are attached to a tetrel atom C or Ge engaged in a XB with nucleophile NH 3 . One, two, and three HF molecules were positioned perpendicular to the XB axis so that they could form a HB to the X atom. Each such HB strengthened the XB by an increment of 1 kcal/mol or more that does not attenuate as each new HB is added, potentially increasing the interaction energy manyfold. Additionally, the presence of one or more HBs facilitates the formation of a XB by molecules which are reluctant to engage in such a bond in the absence of these auxiliary interactions. Even the F atom, which avoids such a XB, can be coaxed to participate in a XB of moderate strength by one or more of these external HBs.

The possibility that two Lewis bases can share a single halogen atom within the context of a bifurcated halogen bond (XB) is explored first by a detailed examination of the CSD. Of the more than 22,000 geometries that fit the definition of an XB (with X = Cl, Br, I), less than 2% are bifurcated. There is a heavy weighting of I in such bifurcated arrangements as opposed to Br, which prefers monofurcated bonds. The conversion from mono to bifurcated is associated with a smaller number of short contact distances, as well as a trend toward lesser linearity. The two XBs within a bifurcated system are somewhat symmetrical: the two lengths generally differ by less than 0.05 Å, and the two XB angles are within several degrees of one another. Quantum calculations of model systems reflect the patterns observed in crystals and reinforce the idea that the negative cooperativity within a bifurcated XB weakens and lengthens each individual bond., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Open and cyclic chains from two to eight units of ICl and IF are constructed and examined by density functional theory (DFT) calculations. These chains contain either I···I or I···X halogen bonds (XBs) where X refers to Cl or F. The closed rings are more stable than the open chains due to the presence of an additional XB and enhanced cooperativity. This pattern is true even for most trimers where there is sizable geometric distortion in the rings. I···F rings are generally more stable than the corresponding I···I cycles as the I···F bond is stronger than I···I even in the simple dimer. However, I···I rings are comparable in energy to I···Cl. It is possible to construct I···I rings of at least as large as eight units, which are held together exclusively by XBs. On the other hand, the maximum possible size of I···X rings is 6. Red shifts are observed in the I-X stretching frequency bands, which magnify as the chain, both cyclic and open, grows longer. The NMR chemical shielding of the I atoms increases for I···I chains but diminishes when I···Cl bonds are present.

The chalcogen Y atom in the aromatic ring of thiophene and its derivatives YC 4 H 4 (Y = S, Se, Te) can engage in a number of different interactions with another such unit within the homodimer. Quantum calculations show that the two rings can be oriented perpendicular to one another in a T-shaped dimer in which the Y atom accepts electron density from the π-system of the other unit in a Y···π chalcogen bond (ChB). This geometry best takes advantage of attractions between the electrostatic potentials surrounding the two monomers. There are two other geometries in which the two Y atoms engage in a ChB with one another. However, instead of a simple interaction between a σ-hole on one Y and the lone pair of its neighbor, the interaction is better described as a pair of symmetrically equivalent Y···Y interactions, in which charge is transferred in both directions simultaneously, thereby effectively doubling the strength of the bond. These geometries differ from what might be expected based simply on the juxtaposition of the electrostatic potentials of the two monomers.

The bonding motif adopted by a dimer of chalcogenadiazole molecules is characterized by a pair of equivalent Ch···N chalcogen bonds. Quantum calculations show that the interaction energy is substantial, varying between 4 kcal/mol for Ch = S and 17 kcal/mol for Te. The interaction is cooperative in that the total bond strength is greater than either chalcogen bond individually. Neither the addition of a phenyl ring nor the addition of a pair of cyano substituents to the diazole ring has much influence on this binding. Removal of one N from the diazole weakens the binding, and addition of two nitrogens has little effect. The largest perturbation arises with three N atoms in each ring, for which the binding energy increases by some 25%. The ring size plays a minor role in most cases, although a near doubling of bond strength occurs if there are two N atoms present on a four-membered ring.

Whereas pnicogen atoms like P and As have been shown repeatedly to act as electron acceptors in pnicogen bonds, the same is not true of the more electronegative first-row N atom. Quantum calculations assess whether N can serve in this capacity in such bonds and under what conditions. There is a positive π-hole belt that surrounds the central N atom in the linear arrangement of NNNF, NNN-CN, and NNO, which can engage a NH 3 base to form a pnicogen bond with binding energy between 3 and 5 kcal/mol. Within the context of a planar arrangement, the π-hole above the N in NO 2 OF, N(CN) 3 , and CF 3 NO 2 is also capable of forming a pnicogen bond, the strongest of which amounts to 11 kcal/mol with NMe 3 as base. In their pyramidal geometry, NF 3 and N(NO 2 ) 3 engage with a base through the σ-hole on the central N, with variable binding energies between 2 and 9 kcal/mol. AIM and NBO provide somewhat different interpretations of the secondary interactions that occur in some of these complexes.

Accompanying the rapidly growing list of σ-hole bonds has come the acknowledgment of parallel sorts of noncovalent bonds which owe their stability in large part to a deficiency of electron density in the area above the molecular plane, known as a π-hole. The origins of these π-holes are probed for a wide series of molecules, comprising halogen, chalcogen, pnicogen, tetrel, aerogen, and spodium bonds. Much like in the case of their σ-hole counterparts, formation of the internal covalent π-bond in the Lewis acid molecule pulls density toward the bond midpoint and away from its extremities. This depletion of density above the central atom is amplified by an electron-withdrawing substituent. At the same time, the amplitude of the π*-orbital is enhanced in the region of the density-depleted π-hole, facilitating a better overlap with the nucleophile's lone pair orbital and a stabilizing n → π* charge transfer. The presence of lone pairs on the central atom acts to attenuate the π-hole and shift its position somewhat, resulting in an overall weakening of the π-hole bond. There is a tendency for π-hole bonds to include a higher fraction of induction energy than σ-bonds with proportionately smaller electrostatic and dispersion components, but this distinction is less a product of the σ- or π-character and more a function of the overall bond strength.

Measuring the strength of the hydrogen bonds between DNA base pairs is of vital importance for understanding how our genetic code is physically accessed and recognized in cells, particularly during replication and transcription. Therefore, it is important to develop probes for these key hydrogen bonds (H-bonds) that dictate events critical to cellular function, such as the localized melting of DNA. The vibrations of carbonyl bonds are well-known probes of their H-bonding environment, and their signals can be observed with infrared (IR) spectroscopy. Yet, pinpointing a single bond of interest in the complex IR spectrum of DNA is challenging due to the large number of carbonyl signals that overlap with each other. Here, we develop a method using isotope editing and infrared (IR) spectroscopy to isolate IR signals from the thymine (T) C2═O carbonyl. We use solvatochromatic studies to show that the TC2═O signal's position in the IR spectrum is sensitive to the H-bonding capacity of the solvent. Our results indicate that C2═O of a single T base within DNA duplexes experiences weak H-bonding interactions. This finding is consistent with the existence of a third, noncanonical CH···O H-bond between adenine and thymine in both Watson-Crick and Hoogsteen base pairs in DNA.

It is well known that the presence of an electron-withdrawing substituent (EWS) placed near the halogen (X) atom on a Lewis acid molecule amplifies the ability of this unit to engage in a halogen bond with a base. Quantum calculations are applied to examine how quickly these effects fade as the EWS is moved further and further from the X atom. Conjugated alkene and alkyne chains of varying lengths with a terminal C-I first facilitate analysis as to how the number of these multiple bonds affects the strength of CI··N XB to NH 3 . Then, electron-withdrawing F and C≡N substituents are placed on the opposite end of the chain, and their effects on the XB properties are monitored as a function of their distance from I. These same EWSs are added to the ortho, meta, and para positions of aromatic iodobenzene. It is found that the XB grows in strength as more triple bonds are added to the alkyne, but there is little change caused by elongating an alkene. The cyano group has a much stronger effect than does F. While F strengthens the XB, its effects are quickly attenuated as it is moved further from I. The consequences of C≡N substitution are stronger and extend over a longer distance. Placement of an EWS on the phenyl ring diminishes with distance: o > m > p , and the effects of disubstitution are nearly additive. These trends apply not only to energetics but also to geometries, properties of the wave function, σ-hole depth, and NMR shielding.

The ability of the T and Z atoms of TR 3 ZR 2 to engage in a noncovalent interaction with NH 3 is assessed by DFT calculations, where the T atom refers to C, Si, and Ge; Z = As, Sb, and P; and substituents R = H and F. In most instances, the tetrel bond (TB) is both stronger and shorter than the pnicogen bond (ZB). These two bond strengths can be equalized, or preference shifted to the ZB, if F substituents are placed on the Z and H on the T atoms. Employing C as the T atom results in a very weak TB, with the ZB clearly favored energetically. The simultaneous formation of both TB and ZB weakens both, particularly the latter, but both bonds survive intact. Geometric and spectroscopic perturbations of the subunits reflect the two types of noncovalent bonds.

The structure of the 5,6-dichloro-2,1,3-benzoselenadiazole homodimer, obtained by adding the ligand, 4,5-dichloro- o -phenylenediamine, to the methanolic solution of SeCl 4 , was determined by X-ray crystallography, augmented by Fourier transform infrared, Raman, and NMR spectroscopy. The binding motif involves a pair of Se···N chalcogen bonds, with a supplementary N···N pnicogen bond. Quantum calculations provide assessments of the strengths of the individual interactions as well as their contributing factors. All together, these three bonds compose a total interaction energy between 5.4 and 16.8 kcal/mol, with the larger chalcogen atom associated with the strongest interactions. Replacement of the Se atoms by S and Te analogues allows analysis of the dependence of these forces on the nature of the chalcogen atom. Calculations also measure the importance to the binding of the presence of a second N atom on each diazole unit as well as the substituted phenyl ring to which it is fused.

The T and X atoms of TF 3 X (T = C, Si, Ge, Sn; X = Cl, Br, I) can engage in a tetrel or halogen bond, respectively, with an approaching NH 3 base. With the exception of T = C, the tetrel bonds are considerably stronger than the halogen bond regardless of the nature of T or X. Because both bonds involve electron acceptance by the central TF 3 X Lewis acid, there is a negative cooperativity between these two bonds when both are present. The halogen bond is weakened much more than is the tetrel bond and is in fact completely disrupted in some cases. Replacement of the three F substituents on TF 3 X by H attenuates the σ-holes on both T and X atoms, weakens and stretches both bonds, and eliminates any halogen bonds involving Cl. Even in those cases where a halogen bond does occur in the dimer, this bond cannot withstand the presence of a simultaneous tetrel bond and so disappears.

A large number of systems were studied that contain either a H-bond (HB) or the closely related halogen (X), chalcogen (Y), or pnicogen (Z) bond. Many of the same relationships between the strength of the HB and spectroscopic parameters apply as well to the other noncovalent bonds. There is a very nearly linear relationship between the interaction energy and the red shift that occurs within the stretching frequency of the pertinent F-A covalent bond of the Lewis acid (where A refers to H, X, Y, or Z). This vibrational mode also undergoes an intensification in all of these bond types, but this quantity is slightly less indicative of the bond strength for XB, YB, and ZB than it is for HB. On the other hand, most of the various noncovalent bonds display a better relationship between energetics and NMR chemical shifts than do the H-bonds, highly auspicious for the use of NMR spectra in diagnosing the presence and strengths of these bonds. An important element in NMR chemical shifts is the internal geometry change induced by complexation.

The question as to whether the F atom can engage in a halogen bond (XB) remains unsettled. This issue is addressed via density functional theory calculations which pair a wide range of organic and inorganic F-acids with various sorts of Lewis bases. From an energetic perspective, perfluorinated hydrocarbons with sp, sp 2 , or sp 3 C-hybridization are unable to form an XB with an N-base, but a very weak bond can be formed if electron-withdrawing C≡N substituents are added to the acid. There is little improvement for inorganic acids O 2 NF, FOF, ClF, BrF, SiF 4 , or GeF 4 , but F 2 is capable of a stronger XB of up to 5 kcal/mol. These results are consistent with a geometric criterion, which compares the intermolecular equilibrium distance with the sum of atomic van der Waals radii. The intensity of the σ-hole on the F atom has predictive value in that a V s,max of at least 10-15 kcal/mol is required for XB formation. Adding a positive charge to the Lewis acid enhances the strength of any XB and even more so if the base is anionic. The acid-base interaction induces a contraction of the r (AF) covalent bond in the acid in most cases and a deshielding of the NMR signal of the F nucleus.

A central pnicogen Z atom (Z = Sb, As) is covalently attached to the O atom of three -O(CH 2 ) n X chains where X represents either an aldehyde or amine group. The chain can fold around so that the basic X group can engage in a noncovalent pnicogen bond with the central Z. The formation of up to three pnicogen bonds is energetically favored. The amine appears to engage in stronger pnicogen bonds than does the aldehyde, and bonds to Sb are favored over As, but there is little dependence on the length of the chain. The formation of each successive pnicogen bond reduces the magnitude of the σ-holes surrounding the Z atom, which tends to weaken the attraction for the basic end of the chain.

The complexation process between anionic ZCl 4 - (Z = P, As, Sb) and neutral NCH and pyridine, as well as the CN - anion, is studied in both the gas phase and aqueous solution by high-level ab initio calculations. Despite the absence of a positively charged σ-hole on ZCl 4 - , a pnicogen bond (ZB) holds all of these complexes together. The dimerization induces the ZCl 4 - to rearrange internally from a see-saw to a square geometry. The complexation process is endothermic for both HCN and CN - in the gas phase but for different reasons. The approach of CN - to ZCl 4 - must overcome anion-anion Coulomb repulsion, while HCN is a much weaker base. The intermediate nucleophilicity of pyridine leads to an exothermic dimerization reaction despite the deformation of the ZCl 4 - structure. The dimers must traverse an energy barrier in order to dissociate. Formation of the dianionic - NC···ZCl 4 - complex becomes exothermic in aqueous solution. Complexation with HCN remains endothermic in water, although less so, and the exothermicity of ZB formation with pyridine is enhanced by solvation.

A central ZF 3 molecule (Z = P, As, Sb, Bi) is allowed to interact with a number of nucleophiles exemplified by NCH, NH 3 , and NC - anion. The Z···N pnicogen bond (ZB) to a single base grows stronger for heavier Z atom: P < A < Sb < Bi and follows the NCH < NH 3 < NC - order for the three bases. The maximum number of ZBs depends on both the nature of the base and pnicogen atom. PF 3 and AsF 3 can pnicogen bond with only a single CN - ; SbF 3 and BiF 3 can interact with two anions but only weakly. The weak NCH nucleophile can engage in a maximum of two ZBs, while three ZBs occur for NH 3 . The latter NH 3 maximum can be extended to four ZBs but only for BiF 3 . The fourth ZB is somewhat longer and weaker than the others, and the entire (H 3 N) 4 ···BiF 3 complex relies partially on secondary interactions for its stability.

Complexes were formed by pairing ZCl 3 (Z = P, As, or Sb) with C 2 R 4 (R = H, F, or CN). The first interaction present is a pnicogen bond between the Z atom and the C═C π-bond. This bond weakens as the H atoms of ethylene are replaced by electron-withdrawing F and CN, and the potential above the alkene switches from negative to positive. In the latter two cases, another set of noncovalent bonds is formed between the Cl lone pairs of ZCl 3 and the π*(C═C) antibonding orbital as well as with the F or CN substituents. The growing strength of these interactions, coupled with a large dispersion energy, more than compensates for the weak pnicogen bond in C 2 (CN) 4 , with its repulsion being between areas of positive charge on each subunit, making its complexes with ZCl 3 very strong, as high as 25 kJ/mol. The pnicogen bond in C 2 F 4 is weaker than in C 2 H 4 , and its subsidiary lone pair-π bonds are weaker than in C 2 (CN) 4 , thus the complexes of this alkene with ZCl 3 are the weakest of the set.

The N-methyltransferase TylM1 from Streptomyces fradiae catalyzes the final step in the biosynthesis of the deoxyamino sugar mycaminose, a substituent of the antibiotic tylosin. The high-resolution crystal structure of TylM1 bound to the methyl donor S-adenosylmethionine (AdoMet) illustrates a network of carbon-oxygen (CH···O) hydrogen bonds between the substrate's sulfonium cation and residues within the active site. These interactions include hydrogen bonds between the methyl and methylene groups of the AdoMet sulfonium cation and the hydroxyl groups of Tyr14 and Ser120 in the enzyme. To examine the functions of these interactions, we generated Tyr14 to phenylalanine (Y14F) and Ser120 to alanine (S120A) mutations to selectively ablate the CH···O hydrogen bonding to AdoMet. The TylM1 S120A mutant exhibited a modest decrease in its catalytic efficiency relative to that of the wild type (WT) enzyme, whereas the Y14F mutation resulted in an approximately 30-fold decrease in catalytic efficiency. In contrast, site-specific substitution of Tyr14 by the noncanonical amino acid p-aminophenylalanine partially restored activity comparable to that of the WT enzyme. Correlatively, quantum mechanical calculations of the activation barrier energies of WT TylM1 and the Tyr14 mutants suggest that substitutions that abrogate hydrogen bonding with the AdoMet methyl group impair methyl transfer. Together, these results offer insights into roles of CH···O hydrogen bonding in modulating the catalytic efficiency of TylM1.

The racemization process of various 1,1'-binaphthyl derivatives is studied by quantum calculations. The preferred racemization pathway passes through a transition state belonging to the C i symmetry group. The energy barrier for this process is independent of solvation, the electron-withdrawing/releasing power of substituents, or their ability to engage in H-bonds within the molecule. The primary factor is instead the substituent size. The barrier is thus reduced when the -OH groups of 1,1'-bi-2-naphthol are replaced by H. There is a drop in the barrier also when the substituents are moved from the 2,2' positions to 6,6', where they will not come close to one another in the transition state. Upon removal of the peripheral aromatic rings of the binaphthyl system, the biphenyl system undergoes a facile racemization. It is concluded that the optimal means of improving optical stability of 1,1'-binaphthyl systems is the substitution of large bulky groups in the 2,2' positions., Competing Interests: The authors declare no competing financial interest.

The synthesis and characterization of a new phthalocyanine (Pc) Mn-nitride complex, ( OEt Pc)MnN (2; OEt Pc = 1,4,8,11,15,18,22,25-octaethoxy-Pc), as well as its stable, readily accessible oxidized (2 + and 2 2+ ) and reduced (2 - , 2 2- ) congeners is reported. This unique isostructural series displays switchable aromatic character spanning the aromatic (2), nonaromatic (2 2+ ), and antiaromatic (2 2- ) triad, in addition to the open-shell radical states (2 + , 2 - ). All complexes were structurally characterized and displayed significant structural distortions at the redox extrema (2 2+ , 2 2- ) consistent with proposed [16 or 18]annulene π ring circuit models. Spectroscopic and computational studies further support these models. This isolated, fully characterized, isostructural series spanning five redox states (2 2+ , 2 + , 2, 2 - , 2 2- ) is unique in both the Pc and related macrocyclic (ex. porphyrinoids) literature and may offer direct insight into structural-electronic correlations driven by switchable aromaticity.

The placement of a nucleophile X along the R-CH 3 axis of a methyl group can be described as either a trifurcated H bond or as a tetrel bond between C and X. Quantum calculations of the vibrational and NMR spectral features of a number of systems are used to provide a framework by which to distinguish between the presence of a tetrel or H bond. Both cationic and neutral methyl-containing Lewis acids (SMe 3 + , NMe 4 + , SMe 2 ) are paired with both neutral and anionic Lewis bases (NH 3 , OH 2 , OCHNH 2 , OCH 3 - , OH - , HCOO - ). As the base is moved away from the R-CH 3 axis of the Lewis acid (tetrel bond) toward a position along a CH axis (CH···X H bond), the methyl stretching frequencies shift to the red, and the bending modes shift to the blue. This modification in the geometry also causes the methyl C atom NMR chemical shielding to increase, while the methyl H atom is progressively deshielded. These changes are of sufficiently large magnitude that they should provide a means to distinguish these two bonding situations from one another.

The C-terminal domain of cobalamin-dependent methionine synthase (MetH) has an essential role in catalyzing the reactivation of the enzyme following the oxidation of its cobalamin cofactor. This reactivation occurs through reductive methylation of the cobalamin using S-adenosylmethionine (AdoMet) as the methyl donor. Herein, we examine the molecular recognition of AdoMet by the MetH reactivation domain utilizing structural, biochemical, and computational approaches. Crystal structures of the Escherichia coli MetH reactivation domain in complex with AdoMet, the methyl transfer product S-adenosylhomocysteine (AdoHcy), and the AdoMet analogue inhibitor sinefungin illustrate that the ligands exhibit an analogous conformation within the solvent-exposed substrate binding cleft of the enzyme. AdoMet binding is stabilized by an intramolecular sulfur-oxygen chalcogen bond between the sulfonium and carboxylate groups of the substrate and by water-mediated carbon-oxygen hydrogen bonding between the sulfonium cation and the side chains of Glu1097 and Glu1128 that bracket the substrate binding cleft. AdoMet and sinefungin exhibited similar binding affinities for the MetH reactivation domain, whereas AdoHcy displayed an affinity for the enzyme that was an order of magnitude lower. Mutations of Glu1097 and Glu1128 diminished the AdoMet/AdoHcy binding selectivity ratio to approximately 2-fold, underscoring the role of these residues in enabling the enzyme to discriminate between the substrate and product. Together, these findings indicate that Glu1097 and Glu1128 in MetH promote high-affinity recognition of AdoMet and that sinefungin and potentially other AdoMet-based methyltransferase inhibitors can abrogate MetH reactivation, which would result in off-target effects associated with alterations in methionine homeostasis and one-carbon metabolism.

The tetravalent character of tetrel atoms leaves only limited room for an incoming nucleophile to approach and engage in a noncovalent bond with a tetrel atom. Any such approach can only occur at the expense of internal geometric distortions. The balance between attractive forces and repulsive steric crowding was studied for a series of Lewis acids of the type FTR 3 (T = Si, Ge, Sn, Pb) which were allowed to interact with various bases. The strength and other properties of the tetrel bond are examined as the R groups are made progressively larger, varying from H and CH 3 to isopropyl and tert-butyl, which induce steric crowding with the incoming base. The effects of crowding which impede the bond can be offset by enlarging the T atom, by adding electron-withdrawing substituents to the Lewis acid, or by considering stronger bases such as anions. The tetrel bond energies reach up to 10 kcal/mol for a pair of neutral molecules with no electron-withdrawing substituents on the Lewis acid. Adding -CF 3 substituents grows the interaction energy to as high as 35 kcal/mol, and a further increment occurs for an anionic base, taking the maximum up to 54 kcal/mol.

Current-voltage hysteresis is a major issue for normal architecture organo-halide perovskite solar cells. In this manuscript we reveal a several-angstrom thick methylammonium iodide-rich interface between the perovskite and the metal oxide. Surface functionalization via self-assembled monolayers allowed us to control the composition of the interface monolayer from Pb poor to Pb rich, which, in parallel, suppresses hysteresis in perovskite solar cells. The bulk of the perovskite films is not affected by the interface engineering and remains highly crystalline in the surface-normal direction over the whole film thickness. The subnanometer structural modifications of the buried interface were revealed by X-ray reflectivity, which is most sensitive to monitor changes in the mass density of only several-angstrom thin interfacial layers as a function of substrate functionalization. From Kelvin probe force microscopy study on a solar cell cross section, we further demonstrate local variations of the potential on different electron-transporting layers within a solar cell. On the basis of these findings, we present a unifying model explaining hysteresis in perovskite solar cells, giving an insight into one crucial aspect of hysteresis for the first time and paving way for new strategies in the field of perovskite-based opto-electronic devices.

Quantum calculations are used to examine the properties of heterodimers formed by a series of tetrel-containing molecules with NH 3 as universal Lewis base. TH 4 was taken as a starting point, with T = C, Si, Ge, and Sn. The H atoms were replaced by various numbers of F atoms-TH 3 F, TF 3 H, and TF 4 -so as to monitor the effects of adding electron-withdrawing substituents. Unsubstituted TH 4 molecules form the weakest tetrel bonds, only up to about 2 kcal/mol. The bond is strengthened when the H opposite NH 3 is replaced by F, rising up to the 6-9 kcal/mol range. Another means of strengthening arises when the three peripheral H atoms of TH 4 are replaced by F. The effect of the latter is heavily dependent on the nature of the T atom and is particularly noticeable for larger tetrels. The two sorts of fluorination patterns are cooperative, in that their combination in TF 4 yields by far the most powerful tetrel bonding agent. The tetrel bond is strengthened as the T atom moves further down the periodic table column. The strongest bond amounts to 25.5 kcal/mol for SnF 4 ··NH 3 . A number of features correlate with the binding energy, but only roughly. These properties include the charge transfer, the AIM bond critical point electron density, the molecular electrostatic potential, and the stretch of the T-X covalent bond upon complex formation.

Receptors for halide anions are constructed based on the imidazolium unit and then replacing the H-bonding C-H group first by halogen-bonding C-I and then by tetrel-bonding C-SnH 3 and C-SiF 3 . Attaching a phenyl ring to any of these species has little effect on its ability to bind a halide, but incorporation of a second imidazolium to the benzene connector, forming a bidentate dicationic receptor, greatly enhances the binding. Addition of electron-withdrawing F atoms to each imidazolium adds a further increment. F - consistently binds more strongly to the various receptor models than does Cl - . Whereas replacement of the H atom on the imidazolium groups with the halogen-bonding I has an inconsistent perturbing effect, tetrel-bonding SnH 3 significantly enhances the binding with either halide, and SiF 3 even more so. Placement of the various complexes into aqueous solution reduces binding energies but the trends that occur in the gas phase are largely reproduced in water. The tetrel-bonding receptors are the most selective for F - over Cl - with an equilibrium ratio on the order of 10 14 for SnH 3 and 10 28 for SiF 3 . When combined with their strong halide binding, SiF 3 -ImF 3 -Bz-ImF 3 -SiF 3 +2 bipodal receptors represent an optimal choice in terms of both binding strength and selectivity.

Temozolomide (TMZ) was paired with each of the five nucleic acid bases, and the potential energy surface searched for all minima, in the context of dispersion-corrected density functional theory and MP2 methods. Three types of arrangements were observed, with competitive stabilities. Coplanar H-bonding structures, reminiscent of Watson-Crick base pairs were typically the lowest in energy, albeit by a small amount. Also very stable were perpendicular arrangements that included one or more H-bonds. The two monomers were stacked approximately parallel to one another in the third category, some of which contained weak and distorted H-bonds. Dispersion was found to be a dominating attractive force, largest for the stacked structures, and smallest for the coplanar dimers.

Quantum calculations are used to study the manner in which quinones interact with proton-donating molecules. For neutral donors, a stacked geometry is favored over a H-bond structure. The former is stabilized by charge transfers from the N or O lone pairs to the quinone's π* orbitals. Following the addition of an electron to the quinone, the radical anion forms strong H-bonded complexes with the various donors. The presence of the donor enhances the electron affinity of the quinone. This enhancement is on the order of 15 kcal/mol for neutral donors, but up to as much as 85 kcal/mol for a cationic donor. The increase in electron affinity is larger for electron-rich quinones than for their electron-deficient counterparts, containing halogen substituents. Similar trends are in evidence when the systems are immersed in aqueous solvent.

Recent studies have demonstrated that carbon-oxygen (CH···O) hydrogen bonds have important roles in S-adenosylmethionine (AdoMet) recognition and catalysis in methyltransferases. Here, we investigate noncovalent interactions that occur between the AdoMet sulfur cation and oxygen atoms in methyltransferase active sites. These interactions represent sulfur-oxygen (S···O) chalcogen bonds in which the oxygen atom donates a lone pair of electrons to the σ antibonding orbital of the AdoMet sulfur atom. Structural, biochemical, and computational analyses of an asparagine mutation in the lysine methyltransferase SET7/9 that abolishes AdoMet S···O chalcogen bonding reveal that this interaction enhances substrate binding affinity relative to the product S-adenosylhomocysteine. Corroborative quantum mechanical calculations demonstrate that sulfonium systems form strong S···O chalcogen bonds relative to their neutral thioether counterparts. An inspection of high-resolution crystal structures reveals the presence of AdoMet S···O chalcogen bonding in different classes of methyltransferases, illustrating that these interactions are not limited to SET domain methyltransferases. Together, these results demonstrate that S···O chalcogen bonds contribute to AdoMet recognition and can enable methyltransferases to distinguish between substrate and product.

The combination of H2C═NH and cis-1,3-butadiene to form a six-membered ring was examined by quantum calculations. The energy barrier for this reaction is substantially lowered by the introduction of an imidazolium catalyst with either a H or halogen (X) atom in the 2-position, which acts via a H or halogen bond to the N atom of the imine, respectively. X = I has the largest effect, and Cl the smallest; Br and H are roughly equivalent. The catalyst retards the formation of the incipient N-C bond from imine to diene while simultaneously accelerating the C-C bond formation. The energy of the π* LUMO of the imine is lowered by the catalyst, which thereby enhances charge transfer from the diene to the imine. Assessment of free energies suggests catalytic rate acceleration by as much as 4-6 orders of magnitude.

The effects of substituent and overall charge upon the binding of a halide anion by a bis(triazolium) receptor are studied by M06-2X DFT calculations, with the aug-cc-pVDZ basis set. Comparison is also made between a receptor that engages in H-bonds, with a halogen-bonding species. Fluoride is clearly most strongly bound, followed by Cl(-), Br(-), and I(-) in that order. The dicationic receptor engages in stronger complexes, but not by a very wide margin compared to its neutral counterpart. The binding is enhanced as the substituent on the two triazolium rings becomes progressively more electron-withdrawing. Halogen-substituted receptors, whether neutral or cationic, display a greater sensitivity to substituent than do their H-bonding counterparts. Both Coulombic and charge transfer factors obey the latter trends but do not correctly reproduce the stronger halogen vs hydrogen bonding. Both H-bonds and halogen bonds are nearly linear within the complexes, due in part to bond rotations within the receptor that bring the two triazole rings closer to coplanarity with the central benzene ring.

The interaction between thiourea and a series of imines was examined via high-level ab initio calculations. For each imine, there is a set of stable complexes that represent minima on the potential energy surface. One type is characterized by a pair of symmetric NH···N hydrogen bonds (HBs), with both NH groups of thiourea approaching the imine N from above and below its molecular plane. Another geometry category combines a linear NH···N with a CH···S HB. A third, which is less stable, has the S approaching the imine's CH2 group, and a stacking arrangement is present in the fourth. Interaction energies vary from ∼2 kcal/mol to a maximum of 13.5 kcal/mol. The formation of the complex tends to elongate the C-N bond within the imine by as much as 0.004 Å, but there are certain dimers that cause a small contraction of this bond.

The ability of neutral and charged S-compounds to form different sorts of noncovalent bonds is examined by ab initio calculations. Neutrals are represented by CH3SH and fluoro-substituted FSCH3; cations are (CH3)3S(+), CH3SH2(+), and FHSCH3(+). Each is paired with N-methylacetamide (NMA) whose O atom serves as a common electron donor. Charged species engage in much stronger noncovalent bonds than do the neutral molecules, by as much as an order of magnitude. The strongest noncovalent bond for any system is a O···SF chalcogen bond wherein the O lies directly opposite a S-F covalent bond, amounting to as much as 39 kcal/mol. Second in binding energy is the SH···O H-bond, which can be as large as 34 kcal/mol. Somewhat weaker is the O···SC chalcogen bond, followed by the CH···O H-bond and finally the O···C tetrel bond, which has the appearance of a trifurcated H-bond. Any CH group that participates in a CH···O H-bond shifts its NMR signal downfield by an amount roughly proportional to the strength of the H-bond. This situation is clearly distinguishable from that in a O···S chalcogen or SH···O H-bond wherein the methyl protons are shifted upfield.

SF2 and SF4 were each paired with a series of unsaturated hydrocarbons including ethene, ethyne, 1,3-butadiene, and benzene, in each case forming a chalcogen bond between the S atom and the carbon π-system. MP2 ab initio calculations reveal that the S atom is situated directly above one specific C═C bond, even when more than one are present. The binding energies range between 3.3 and 6.6 kcal/mol. SF2 engages in a stronger, and shorter, noncovalent bond than does SF4 for all systems with the exception of benzene, to which SF4 is more tightly bound. cis-Butadiene complexes contain the shortest chalcogen bond, even if not necessarily the strongest. The internal S-F covalent bonds elongate upon formation of each chalcogen bond. The molecules are held together largely by charge transfer forces, particularly from the C═C π-bonds to the σ*(SF) antibonding orbitals. In the case of SF2, a sulfur lone pair can transfer charge into the π* MOs of the alkene, a back-transfer which is more difficult for SF4.

Density functional methods are used to examine the geometries and energetics of molecules containing a phenyl ring joined to the trigonal bipyramidal SF3 framework. The phenyl ring has a strong preference for an equatorial position. This preference remains when one or two ether -CH2OCH3 groups are added to the phenyl ring, ortho to SF3, wherein an apical structure lies nearly 30 kcal/mol higher in energy. Whether equatorial or apical, the molecule is stabilized by a S···O chalcogen bond, sometimes augmented by CH···F or CH···O H-bonds. The strength of the intramolecular S···O bond is estimated to lie in the range between 3 and 6 kcal/mol. A secondary effect of the S···O chalcogen bond is elongation of the S-F bonds. Solvation of the molecule strengthens the S···O interaction. Addition of substituents to the phenyl ring has only modest effects upon the S···O bond strength. A strengthening arises when an electron-withdrawing substituent is placed ortho to the ether and meta to SF3, while electron-releasing species produce an opposite effect.

SOF2, SOFCl, and SOCl2 were each paired with a series of N bases. The potential energy surface of the binary complexes were characterized by MP2 calculations with double and triple-ξ basis sets, extrapolated to complete sets. The most stable configurations contained a S···N chalcogen bond with interaction energies as high as 6.8 kcal/mol. These structures are stabilized by a Nlp → σ*(S-Z) electron transfer (Z = O, F, Cl), complemented by Coulombic attraction of N to the σ-hole opposite the Z atom. N···S-F and N···S-Cl chalcogen bonds are stronger than N···S═O interactions. Formation of each chalcogen bond elongates all of the internal covalent bonds within SOXY, especially the S-Cl bond. Halogen-bonded (N···Cl-S) complexes were also observed, but these are more weakly bound, by less than 3 kcal/mol.

The N···S chalcogen bond between SF4 and a series of alkyl and arylamines is examined via ab initio calculations. This bond is a strong one, with a binding energy that varies from a minimum of 7 kcal/mol for NH3 to 14 kcal/mol for trimethylamine. Its strength derives in large measure from charge transfer from the N lone pair into the σ*(SF) antibonding orbitals involving the two equatorial F atoms, one of which is disposed directly opposite the N atom. Decomposition of the total interaction energy reveals that the induction energy constitutes more than half of the total attraction. The positive region of the molecular electrostatic potential of SF4 that lies directly opposite the equatorial F atoms is attracted to the N lone pair, but the magnitude of this negative region on each amine is a poor predictor of the binding energy. The shortness and strength of the N···S bond in the dimethylamine···SF4 complex suggest it may better be described as a weak covalent bond.

The CH···π hydrogen bonds (HBs) between trimethylamine (TMA) and an assortment of π-systems are generally weaker than those in which CF3H serves as a proton donor, despite the larger number of CH groups available to serve as donors in the amine. The added positive charge of tetramethylammonium (TMA+) enhances the binding energy by a factor between 4 and 7. The strongest such interaction for TMA+ occurs with indole, bound by 15.5 kcal/mol. Changing from ionic CH···π to NH···π further strengthens the interaction. Conjugation of the π-system improves its proton-accepting capacity, which is further enhanced by aromaticity. Dispersion plays a major role in CH···π HBs: It is the prime contributor in the neutral HBs of TMA, and comparable to Coulombic forces for CF3H and even in ionic CH···π HBs of TMA+. Many of the results can be understood on the basis of a combination of electrostatic potentials and charge transfers.

Recent studies have demonstrated that the active sites of S-adenosylmethionine (AdoMet)-dependent methyltransferases form strong carbon-oxygen (CH···O) hydrogen bonds with the substrate's sulfonium group that are important in AdoMet binding and catalysis. To probe these interactions, we substituted the noncanonical amino acid p-aminophenylalanine (pAF) for the active site tyrosine in the lysine methyltransferase SET7/9, which forms multiple CH···O hydrogen bonds to AdoMet and is invariant in SET domain enzymes. Using quantum chemistry calculations to predict the mutation's effects, coupled with biochemical and structural studies, we observed that pAF forms a strong CH···N hydrogen bond to AdoMet that is offset by an energetically unfavorable amine group rotamer within the SET7/9 active site that hinders AdoMet binding and activity. Together, these results illustrate that the invariant tyrosine in SET domain methyltransferases functions as an essential hydrogen bonding hub and cannot be readily substituted by residues bearing other hydrogen bond acceptors.