Non-Classical Synthons: Supramolecular Recognition by S⋅⋅⋅O Chalcogen Bonding in Molecular Complexes of Riluzole

Classical examples of supramolecular recognition units or synthons are the ones formed by hydrogen bonds. Here, we report the ubiquity of a S⋅⋅⋅O chalcogen bonded synthon observed in a series of supramolecular complexes of the amyotrophic lateral sclerosis drug riluzole. Although the potential of higher chalcogens such as Se and Te to form robust and directional chalcogen bonded motifs is known, intermolecular sulfur chalcogen bonding is considered to be weak owing to the lower polarizability of S atoms. Here, the robustness and electronic nature of a S⋅⋅⋅O chalcogen bonding non-classical synthon, and the origin of its exceptional directionality have been explored. Bond orders of the drug–coformer chalcogen bonding are found to be as high as one third of a single bond, and they are largely ionic in nature. The contribution of the S⋅⋅⋅O chalcogen bonded motifs to the lattice energies of a series of crystals from the Cambridge Structural Database has been analyzed, showing they can be indeed significant, especially in molecules devoid of strong hydrogen bond donor groups.     

Double Chalcogen Bonds: Crystal Engineering Stratagems via Diffraction and Multinuclear Solid-State Magnetic Resonance Spectroscopy

Group 16 chalcogens potentially provide Lewis-acidic σ-holes, which are able to form attractive supramolecular interactions with electron rich partners through chalcogen bonds. Here, a multifaceted experimental and computational study of a large series of novel chalcogen-bonded cocrystals, prepared using the principles of crystal engineering, is presented. Single-crystal X-ray diffraction studies reveal that dicyanoselenadiazole and dicyanotelluradiazole derivatives work as promising supramolecular synthons with the ability to form double chalcogen bonds with a wide range of electron donors including halides and oxygen- and nitrogen-containing heterocycles. Extensive ⁷⁷Se and ¹²⁵Te solid-state nuclear magnetic resonance spectroscopic investigations of cocrystals establish correlations between the NMR parameters of selenium and tellurium and the local chalcogen bonding geometry. The relationships between the electronic environment of the chalcogen bond and the ⁷⁷Se and ¹²⁵Te chemical shift tensors were elucidated through a natural localized molecular orbital density functional theory analysis. This systematic study of chalcogen-bond-based crystal engineering lays the foundations for the preparation of the various multicomponent systems and establishes solid-state NMR protocols to detect these interactions in powdered materials.     

Charge-Assisted Chalcogen Bonds: CSD and DFT Analyses and Biological Implication in Glucosidase Inhibitors

This study reports a combined Cambridge Structural Database and theoretical DFT study of charge assisted chalcogen bonds involving sulfonium, selenonium, and telluronium cations. The chalcogen bond has been recently defined by IUPAC as the net attractive interaction between an electrophilic region associated with a chalcogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. Divalent chalcogen atoms typically have up to two σ-holes and forms up to two ChBs; the same holds for tetravalent chalcogens which adopt a seesaw arrangement. In sulfonium, selenonium, and telluronium salts chalcogen atoms form three covalent bonds, three σ-holes are located opposite to these bonds, and up to three charge assisted ChBs can be formed between these holes and the counterions. The covalent bond arrangement around these chalcogen atoms is similar to trivalent pnictogen atoms and translates into a similar pattern of noncovalent interactions. We have found and studied this type of charge-assisted chalcogen bonds in various sulfonium ion-containing inhibitors of glucosidase, for example, salacinol and kotalanol.     

Toward a general mechanism of electron capture dissociation

The effects of positive charge on the properties of ammonium and amide radicals were investigated by ab initio and density functional theory calculations with the goal of elucidating the energetics of electron capture dissociation (ECD) of multiply charged peptide ions. The electronic properties of the amide group in N-methylacetamide (NMA) are greatly affected by the presence of a remote charge in the form of a point charge, methylammonium, or guanidinium cations. The common effect of the remote charge is an increase of the electron affinity of the amide group, resulting in exothermic electron capture. The N-Calpha bond dissociation and transition state energies in charge-stabilized NMA anions are 20-50 kJ mol(-1) greater than in the hydrogen atom adduct. The zwitterions formed by electron capture have proton affinities that were calculated as 1030-1350 kJ mol(-1), and are sufficiently basic for the amide carbonyl to exothermically abstract a proton from the ammonium, guanidinium and imidazolium groups in protonated lysine, arginine, and histidine residues, respectively. A new mechanism is proposed for ECD of multiply charged peptide and protein cations in which the electron enters a charge-stabilized electronic state delocalized over the amide group, which is a superbase that abstracts a proton from a sterically proximate amino acid residue to form a labile aminoketyl radical that dissociates by N-Calpha bond cleavage. This mechanism explains the low selectivity of N-Calpha bond dissociations induced by electron capture, and is applicable to dissociations of peptide ions in which the charge carriers are metal ions or quaternary ammonium groups. The new amide superbase and the previously proposed mechanisms of ECD can be uniformly viewed as being triggered by intramolecular proton transfer in charge-reduced amide cation-radicals. In contrast, remote charge affects N-H bond dissociation in weakly bound ground electronic states of hypervalent ammonium radicals, as represented by methylammonium, CH3NH3*, but has a negligible effect on the N-H bond dissociation in the strongly bound excited electronic states. This refutes previous speculations that loss of "hot hydrogen" can occur from an excited state of an ammonium radical.     

Triplet excited states of cyclic disulfides and related compounds: electronic structures, geometries, energies, and decay

We have performed a computational study on the properties of a series of heterocycles bearing two adjacent heteroatoms, focusing on the structures and electronic properties of their first excited triplet states. If the heteroatoms are both heavy chalcogens (S, Se, or Te) or isoelectronic species, then the lowest excited triplet state usually has (π*, σ*) character. The triplet energies are fairly low (30-50 kcal mol(-1)). The (π*, σ*) triplet states are characterized by a significantly lengthened bond between the two heteroatoms. Thus, in 1,2-dithiolane (1b), the S-S bond length is calculated to be 2.088 ? in the singlet ground state and 2.568 ? in the first triplet excited state. The spin density is predicted to be localized almost exclusively on the sulfur atoms. Replacing one heavy chalcogen atom by an oxygen atom or an NR group results in a significant destabilization of the (π*, σ*) triplet excited state, which then no longer is lower in energy than an open-chain biradical. The size of the heterocyclic ring also contributes to the stability of the (π*, σ*) triplet state, with five-membered rings being more favorable than six-membered rings. Benzoannulation, finally, usually lowers the energy of the (π*, σ*) triplet excited states. If one of the heteroatoms is an oxygen or nitrogen atom, however, the corresponding lowest triplet states are better described as σ,π-biradicals.     

Theoretical investigation of the (hyper)polarizabilities of pyrrole homologues C4H4XH (X = N, P, As, Sb, Bi). A coupled-cluster and density functional theory study

Geometries, inversion barriers, static and dynamic electronic and vibrational dipole polarizability (alpha), and first (beta) and second (gamma) hyperpolarizability of the pyrrole homologues C(4)H(4)XH (X = N, P, As, Sb, Bi) have been calculated by Hartree-Fock, M?ller-Plesset second-order perturbation theory, coupled-cluster theory accounting for singles, doubles, and noniterative triple excitations methods, as well as density functional theory using B3LYP and PBE1PBE functionals and Sadlej's Pol and 6-311G basis sets. Relativistic effects on the heavier homologues stibole and bismole have been taken into account within effective core potential approximation. The results show that the electronic (hyper)polarizabilities monotonically increase with the atomic number of the heteroatom, consistent with the decrease in the molecular hardness. Ring planarization reduces the carbon-carbon bond length alternation of the cis-butadienic unit, enhancing the electronic polarizability values (alpha(e)) by 4-12% and the (hyper)polarizability values (and gamma(e)) by 30-90%. Pure vibrational and zero-point vibrational average contributions to the (hyper)polarizabilities have been determined within the clamped nucleus approach. In the static limit, the pure vibrational hyperpolarizabilities have a major contribution. Anharmonic corrections dominate the pure vibrational hyperpolarizabilities of pyrrole, while they are less important for the heavier homologues. Static and dynamic electronic response properties of the pyrrole homologues are comparable to or larger than the corresponding properties of the furan and cyclopentadiene homologue series.     

Halogen and Chalcogen Bond Energies Evaluated Using Electron Density Properties

Halogen (X-bond) and chalcogen bond (Ch−bond) energies for 36 complexes have been obtained at the RI-MP2/def2−TZVP level of theory, involving the heavier halogen and chalcogen atoms (Br, I, Se, Te). We have explored the existence of linear relationships between the interaction energies and the local kinetic energy densities at the bond critical points that characterize the σ-hole interactions (both electronic G(r) and potential V(r) energy densities). Interestingly, we have found strong relationships for halogen and chalcogen bonding energies, especially for the V(r) energy density, thus allowing to estimate the interaction energy without computing the separate monomers. This is also useful to estimate the interaction in monomeric systems (intramolecular X/Ch-bonds), as illustrated using several examples. Remarkably, we have also found a good relationship when in the same representation both halogen and chalcogen atoms are included, thus allowing to use the same empirical correlation for both interactions.     

Design principles for alpha-tocopherol analogues

An (RO)B3LYP/LANL2DZdp//B3LYP/LANL2DZ model for the prediction of the homolytic bond dissociation enthalpy (BDE) and adiabatic ionisation potential (IP) of phenolic antioxidants containing heavy chalcogens has been developed. The model has been used to probe the relationship between geometry, chalcogen substitution and activity for a series of alpha-tocopherol analogues of varying ring size. From this, a series of design principles for cyclic antioxidants has emerged, embodied by the compound 4-hydroxy-2,2,3,5,6-pentamethylbenzoselenete (4c). This compound is predicted to have a BDE comparable to alpha-tocopherol, and should act in a dual chain-breaking and hydroperoxide-decomposing manner, by analogy with other selenide antioxidants. The stability of chalcogen-substituted benzoxetes was considered, and the as yet unsynthesised benzotelluretes are predicted to be stable. Finally, an attempt was made to determine antioxidant mechanism by considering calculated BDE and IP data together with experimental rate data.     

亚甲基富勒烯衍生物[6，6]-苯基-C61丁酸甲酯的密度泛函研究

运用密度泛函理论和含时密度泛函理论研究了亚甲基富勒烯衍生物[6.6]-苯基-C61丁酸甲酯(PCBM)的几种物理化学性质,包括几何结构、电子结构、电荷布居与成键,以及IR、Raman和电子吸收光谱.自然键轨道方法的结果表明,大约有0.11个电子通过成键由分子的一部分苯基和丁酸甲酯基团(电子给体)转移到富勒烯笼(电子受体).最强的IR和Raman谱峰来自于不同的振动模式,分别位于1773和1492 cm-1处.计算的各向同性极化率、极化率各向异性不变量以及超极化率分别是577.7、96.9、-22.8 a.u..基于含时密度泛函理论计算并分析了PCBM的电子吸收谱,在349 nm处的吸收峰与实验结果符合很好.     

亚甲基富勒烯衍生物[6,6]-苯基-C61丁酸甲酯的密度泛函研究

运用密度泛函理论和含时密度泛函理论研究了亚甲基富勒烯衍生物[6,6]-苯基-C61丁酸甲酯(PCBM)的几种物理化学性质, 包括几何结构、电子结构、电荷布居与成键, 以及IR、Raman和电子吸收光谱. 自然键轨道方法的结果表明, 大约有0.11个电子通过成键由分子的一部分苯基和丁酸甲酯基团(电子给体)转移到富勒烯笼(电子受体). 最强的IR和Raman谱峰来自于不同的振动模式, 分别位于1773和1492 cm-1处. 计算的各向同性极化率、极化率各向异性不变量以及超极化率分别是577.7、96.9、-22.8 a.u.. 基于含时密度泛函理论计算并分析了PCBM的电子吸收谱, 在349 nm处的吸收峰与实验结果符合很好.     

Trialkylphosphine-stabilized copper(I) gallium(III) phenylchalcogenolate complexes: crystal structures and generation of ternary semiconductors by thermolysis

A series of organometallic trialkylphosphine-stabilized copper gallium phenylchalcogenolate complexes [(R(3)P)(m)Cu(n)Me(2-x)Ga(EPh)(n+x+1)] (R = Me, Et, (i)Pr, (t)Bu; E = S, Se, Te; x = 0, 1) has been prepared and structurally characterized by X-ray diffraction. From their molecular structures three groups of compounds can be distinguished: ionic compounds, ring systems, and cage structures. All these complexes contain one gallium atom bound to one or two methyl groups, whereas the number of copper atoms, and therefore the nuclearity of the complexes, is variable and depends mainly on size and amount of phosphine ligand used in synthesis. The Ga-E bonds are relatively rigid, in contrast to flexible Cu-E bonds. The lengths of the latter are controlled by the coordination number and steric influences. The Ga-E bond lengths depend systematically on the number of methyl groups bound to the gallium atom, with somewhat shorter bonds in monomethyl compounds compared to dimethyl compounds. Quantum chemical computations reproduce this trend and show furthermore that the rotation of one phenyl group around the Ga-E bond is a low energy process with two distinct minima, corresponding to two different conformations found experimentally. Mixtures of different types of chalcogen atoms on molecular scale are possible, and then ligand exchange reactions in solution lead to mixed site occupation. In thermogravimetric studies the complexes were converted into the ternary semiconductors CuGaE(2). The thermolysis reaction is completed at temperatures between 250 and 400 °C, typically with lower temperatures for the heavier chalcogens. Because of significant release of Me(3)Ga during the thermolysis process, and especially in case of copper excess in the precursor complexes, binary copper chalcogenides are obtained as additional thermolysis products. Quaternary semiconductors can be obtained from mixed chalcogen precursors.     

DFT Study on Methanofullerene Derivative [6,6]-Phenyl-C61 Butyric Acid Methyl Ester

Density functional theory (DFT) and time-dependent density functional theory (TDDFT) with hybrid functional B3LYP were used to investigate several physical and chemical properties of [6,6]-phenyl-C₆₁ butyric acid methyl ester (PCBM), including the geometry, electron structure, charge population, bond properties, as well as IR, Raman and electronic absorption spectra. The analysis of the natural bond orbital (NBO) suggested that there were about 0.11 electrons transferred from moiety phenyl and butyric acid methyl ester group of PCBM to fullerene cage. The strongest IR and Raman peaks came from different modes with the frequencies of 1773 and 1492 cm⁻¹, respectively. The calculated isotropic polarizability, polarizability anisotropy invariant, and hyperpolarizability were 577.7, 96.9, and −22.8 a.u., respectively. Based on TDDFT, the electronic absorption spectra of PCBM were calculated and analyzed. The calculated absorption band near 349 nm agreed well with the experimental measurement.     

Finely Tuned Electron/Hole Transport Preference of Thiazoloisoindigo-based Conjugated Polymers by Incorporation of Heavy Chalcogenophenes

A series of copolymers of thiazoloisoindigo(TzII) with different chalcogenophene trimers were synthesized to systematically investigate the chalcogen effect on their charge transport properties. When only the middle thiophene ring of terthiphene(T-T-T) is replaced by heavier chalcogenophenes, a preference(expressed by the ratio of μ_e/μ_h) towards electron transport was observed descending from T-T-T to T-Se-T then to T-Te-T(Se and Te stand for selenophene and tellurophene, respectively). On the other hand, with the increased number of heavier chalcogenophenes, a preference toward hole transport was observed descending from Se-T-Se to Se-Se-Se then to Se-Te-Se. This phenomenon is well-explained by the balance between the aromatic resonance energy of the chalcogenophenes and the electronegativity of the chalcogens.Specifically, P(TzII-T-Se-T) displayed relatively balanced ambipolar property(μ_h~(max) and μ_e~(max) of 3.77 and 1.59 cm~2·V~(-1)·s~(-1) with a μ_e/μ_h of 0.42),while P(TzII-Se-Te-Se) exhibited the best preference to hole transfer with a μ_e/μ_h of 0.09. P(TzII-T-Te-T) exhibited the best preference to electron transfer with a μ_e/μ_h of 16 and the μ_e~(max) of 0.64 cm~2·V~(-1)·s~(-1) which is the highest electron mobility among the known conjugated polymers containing tellurophenes.     

1,2,3-Triazoles as Biomimetics in Peptide Science

Natural peptides are an important class of chemical mediators, essential for most vital processes. What limits the potential of the use of peptides as drugs is their low bioavailability and enzymatic degradation in vivo. To overcome this limitation, the development of new molecules mimicking peptides is of great importance for the development of new biologically active molecules. Therefore, replacing the amide bond in a peptide with a heterocyclic bioisostere, such as the 1,2,3-triazole ring, can be considered an effective solution for the synthesis of biologically relevant peptidomimetics. These 1,2,3-triazoles may have an interesting biological activity, because they behave as rigid link units, which can mimic the electronic properties of amide bonds and show bioisosteric effects. Additionally, triazole can be used as a linker moiety to link peptides to other functional groups.     

Effect of double-hyperconjugation on the apparent donor ability of sigma-bonds: insights from the relative stability of delta-substituted cyclohexyl cations

A combination of electronic, structural, and energetic analyses shows that a somewhat larger intrinsic donor ability of the C-H bonds compared to that of C-C bonds can be overshadowed by cooperative hyperconjugative interactions with participation of remote substituents (double hyperconjugation or through-bond interaction). The importance of double hyperconjugation was investigated computationally using two independent criteria: (a) relative total energies and geometries of two conformers ("hyperconjomers") of delta-substituted cyclohexyl cations (b) and natural bond orbital (NBO) analysis of electronic structure and orbital interactions in these molecules. Both criteria clearly show that the apparent donor ability of C-C bonds can vary over a wide range, and the relative order of donor ability of C-H and C-C bonds can be easily inverted depending on molecular connectivity and environment. In general, relative donor abilities of sigma bonds can be changed by their through-bond communication with remote substituents and by greater polarizability of C-X bonds toward heavier elements. These computational results can be confirmed by experimental studies of conformational equilibrium of delta-substituted cyclohexyl cations.     

Understanding the dielectric properties of liquid amides from a polarizable force field

The role played by electronic polarization in the dielectric properties of liquid N-methyl acetamide (NMA) is examined using molecular dynamics simulations with a polarizable force field based on classical Drude oscillators. The model presented is the first force field shown to reproduce the anomalously large dielectric constant of liquid NMA. Details of the molecular polarizability are found to be important. For instance, all elements of the polarizability tensor, rather then just the trace, impact on the condensed phase properties. Two factors related to electronic polarizability are found to contribute to this large dielectric constant. First is the significant enhancement of the mean amide molecular dipole magnitude, which is 50% larger in the liquid than in the gas phase. Second is the consequent strong hydrogen bonding between molecular neighbors that enhances the orientational alignment of the molecular dipoles. Polarizable models of amide compounds that have two (acetamide) and zero (N,N-dimethyl acetamide) polar hydrogen-bond donor atoms are also investigated. Experimentally, the neat liquid dielectric constants at 373 K are 100 for NMA, 66 for acetamide and 26 for N,N-dimethyl acetamide. The polarizable models replicate this trend, predicting a dielectric constant of 92+/-5 for NMA, 66+/-3 for acetamide and 23+/-1 for N,N-dimethyl acetamide.     

Comparison between Hydrogen and Halogen Bonds in Complexes of 6-OX-Fulvene with Pnicogen and Chalcogen Electron Donors

Quantum chemical calculations are applied to complexes of 6-OX-fulvene (X=H, Cl, Br, I) with ZH₃/H₂Y (Z=N, P, As, Sb; Y=O, S, Se, Te) to study the competition between the hydrogen bond and the halogen bond. The H-bond weakens as the base atom grows in size and the associated negative electrostatic potential on the Lewis base atom diminishes. The pattern for the halogen bonds is more complicated. In most cases, the halogen bond is stronger for the heavier halogen atom, and pnicogen electron donors are more strongly bound than chalcogen. Halogen bonds to chalcogen atoms strengthen in the order O<S<Se<Te, whereas the pattern is murkier for the pnicogen donors. In terms of competition, most halogen bonds to pnicogen donors are stronger than their H-bond analogues, but there is no clear pattern with respect to chalcogen donors. O prefers a H-bond, while halogen bonds are favored by Te. For S and Se, I-bonds are strongest, followed Br, H, and Cl-bonds in that order.     

Mechanism and energetics of intramolecular hydrogen transfer in amide and peptide radicals and cation-radicals

Intramolecular hydrogen transfer in five model amide and peptide radicals and cation-radicals was investigated by combined B3LYP-MP2 calculations. Hypervalent ammonium radicals produced by electron capture in protonated peptides undergo competitive elimination of ammonia, H-atom loss, and H-atom migration to neighboring amide carbonyls. The calculated transition state energies for H-atom migration are slightly but uniformly lower than those for H-atom loss. Transition state theory calculations with inclusion of quantum tunneling effects predict k(H migration)/k(H loss) branching ratios that increase with the ring size of the cyclic transition state for the migration. Intramolecular hydrogen-atom migration in amide and peptide radicals can be described by the proton-coupled electron transfer mechanism. The migrating hydrogen atom shows a negligible spin density and substantial positive charge that are typical of a proton migration. Electron transfer occurs through a pi-orbital system and proceeds in the same (clockwise) or opposite (counterclockwise) direction as the proton motion, depending on the electronic properties of the chain connecting the ammonium group and the amide bond.     

M，W型六角钡铁氧体化学键性质和穆斯堡尔谱位移研究

利用电介质的平均能带模型研究了M型、W型六角铁氧体的化学成键性质,计算了各晶位的共价性的穆斯堡尔同质异能位移,结果与实验值一致,确定了Fe^2+在W型铁氧体中所占晶位。