Packing Forces Research Articles

Isolation of a Square-Planar Th(III) Complex: Synthesis and Structure of [Th(OC6H2tBu2-2,6-Me-4)4]1.

Reduction of Th(OC6H2tBu2-2,6-Me-4)4 using either KC8 or Li in THF forms a new example of a crystallographically characterizable Th(III) complex in the salts [K(THF)5(Et2O)][Th(OC6H2tBu2-2,6-Me-4)4] and [Li(THF)4][Th(OC6H2tBu2-2,6-Me-4)4]. Surprisingly, in each structure the four aryloxide ligands are arranged in a square-planar geometry, the first example of this coordination mode for an f element complex. The Th(III) ion and four oxygen donor atoms are coplanar to within 0.05 Å with O-Th-O angles of 89.27(8) to 92.02(8)° between cis ligands. The ligands have Th-O-C(ipso) angles of 173.9(2) to 178.6(4)°, and the aryl rings make angles of 58.5 to 65.1° with the ThO4 plane. The effect of the eight tert-butyl substituents in generating the unusual structure through packing and/or dispersion forces is discussed. EPR spectroscopy reveals an axial signal consistent with a metal-based radical in a planar complex. DFT calculations yield a C4-symmetric structure that accommodates a low-lying SOMO of 6dz2 character with 7s Rydberg admixture.

Solvent Dependent Prototropic Tautomerism in a Schiff Base Derived from o‐Vanillin and 2‐Aminobenzylalcohol

AbstractThe Schiff base H2L, namely 2‐(3‐methoxysalicylidene‐amino)‐benzyl‐alcohol, 1 and its two pseudo‐polymorphs H2L⋅CH3OH 2 and H2L⋅H2O 3, have been synthesized by the condensation reaction of 2‐aminobenzyl alcohol and o‐vanillin in different solvents. X‐ray crystallographic analysis revealed that the keto‐enol tautomerism of H2L in solid state exists as a complex system of three different enol, keto and zwitterionic forms in equilibrium, dependent on crystal packing forces and the crystallization solvent. The enol, keto and mixed enol‐zwitterionic (roughly 1:1) forms were observed in the crystal structures of 1, 2 and 3, respectively. The crystallographic results are supported by FTIR and DFT calculations. Photophysical properties were determined in acetonitrile solution and solid state and were supported by TD‐DFT studies.

Dimethylphenylphosphine oxide coordinated trivalent rhenium featuring pyridylbenzazole chelation: Oxygen atom transfer kinetics, isomer preference, metal oxidation and computational analysis

The present work embodies outward oxygen atom transfer (OAT) reaction from pyridylbenzoxazole (L1) chelated oxorhenium(V) complex of type [ReOCl3(L1)], 1 towards oxophilic PMe2Ph resulting in the formation of reduced Re(III) derivative [Re(OPMe2Ph)Cl3(L1)], 4 containing oxidised phosphine trans to azole nitrogen. Another possible isomer (4a) having oxidised phosphine trans to pyridyl nitrogen has not been isolated. Structural elucidation of 4 reveals meridional disposition of three Cl atoms around the metal featuring distorted octahedral geometry. DFT analysis of isomers of type [Re(OPMe2Ph)Cl3(L1)] (4 and 4a) confirms isoenergetic nature in gas phase, however, stereospecific binding of L1 to Re(III) centre affording 4 as exclusive product is attributed to crystal packing force. 1 → 4 redox transformation has also been attended with the change in singlet → triplet spin state of the metal. Triplet state of 4 is more stable by ca. 15 kcal mol−1 compared to the singlet state in gas phase. Two electron paramagnetic nature (2.13 μB) in solid state affirms triplet ground state characterised with strong orbital coupling. Kinetic data for 1 → 4 transformation suggests associative pathway (ΔS≠ = ∼−36 J/K/mol) with no major structural reorganisation in the primary coordination sphere of the substrate and the reagent (ΔH≠ = ∼+10 kcal mol−1) to reach the transition state. Pyridylbenzthiazole (L2) chelated oxorhenium(V) complex of type [ReOCl3(L2)], 1b also reacts with PMe2Ph in a same manner to from [Re(OPMe2Ph)Cl3(L2)], 4b where the pyridyl nitrogen lies trans to phosphineoxide moiety unlike 4. The second order rate constants of OAT to PMe2Ph for [ReOCl3(L1)] are nearly two times higher than that of [ReOCl3(L2)] at all recorded temperatures due to difference in azole heteroatom electronegativity, ReVO bond length and ReVI/ReV reduction potential.

Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes.

The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into the gating mechanisms of thermoTRPV channels. Interestingly, crystallographic studies of ligand-dependent TRPV2 gating have shown that the TRPV2 channel adopts two-fold symmetric arrangements during the gating cycle. However, it was unclear if crystal packing forces played a role in stabilizing the two-fold symmetric arrangement of the channel. Here, we employ cryo-EM to elucidate the structure of full-length rabbit TRPV2 in complex with the agonist resiniferatoxin (RTx) in nanodiscs and amphipol. We show that RTx induces two-fold symmetric conformations of TRPV2 in both environments. However, the two-fold symmetry is more pronounced in the native-like lipid environment of the nanodiscs. Our data offers insights into a gating pathway in TRPV2 involving symmetry transitions.

Dicyclopenta[ghi,pqr]perylene as a Structural Motif for Bowl-Shaped Hydrocarbons: Synthetic and Conformational Studies.

Dicyclopenta[ghi,pqr]perylene (DCPP) is a substructural fragment on the surface of C70 yet not on C60. Unlike its intensely investigated buckybowl cousins, corannulene and sumanene, DCPP is largely ignored due to the lack of synthetic accessibility. This communication describes the first preparation of a DCPP derivative from bay substituted perylene bis(4-(trifluoromethyl)phenyl)methanol as the key cyclization precursor. Further incorporation of indeno substitutions at peri positions was accomplished through Suzuki-Heck benzannulation. DCPP derivatives 4 adopts a planar structure in crystal. On the contrary, indeno DCPP 5 and bis-indeno DCPP 6 adopt the bowl-shaped conformation in both the solid state and solution. Density functional theory (DFT) calculation reveals that the lowest-energy conformations of 4, 5, and 6 are all bowl-shaped. Nevertheless, small bowl-to-bowl inversion barrier for 4 (3.4 kcal/mol) is overcome by the crystal packing force, which leads to its observed planar structure. However, the bowl-shaped structures of 5 and 6 are affirmed by DFT calculation with intermediate and high bowl-to-bowl inversion barriers (10.4 and 18.5 kcal/mol, respectively).

Stereochemistry of polypeptoid chain configurations.

Like polypeptides, peptoids, or N-substituted glycine oligomers, have intrinsic conformational preferences due to their amide backbones and close spacing of side chain substituents. However, the conformations that peptoids adopt are distinct from polypeptides due to several structural differences: the peptoid backbone is composed of tertiary amide bonds that have trans and cis conformers similar in energy, they lack a backbone hydrogen bond donor, and have an N-substituent. To better understand how these differences manifest in actual peptoid structures, we analyzed 46 high quality, experimentally determined peptoid structures reported in the literature to extract their backbone conformational preferences. One hundred thirty-two monomer dihedral angle pairs were compared to the calculated energy landscape for the peptoid Ramachandran plot, and were found to fall within the expected minima. Interestingly, only two regions of the backbone dihedral angles ϕ and ψ were found to be populated that are mirror images of each other. Furthermore, these two conformers are present in both cis and trans forms. Thus, there are four primary conformers that are sufficient to describe almost all known backbone conformations for peptoid oligomers, despite conformational constraints imposed by a variety of side chains, macrocyclization, or crystal packing forces. Because these conformers are predominant in peptoid structure, and are distinct from those found in protein secondary structures, we propose a simple naming system to aid in the description and classification of peptoid structure.

Supramolecular polymers derived from the PtII and PdII schiff base complexes via C(sp2)–H … Hal hydrogen bonding: Combined experimental and theoretical study

A synthesis of the PdII and PtIIN,N-diaryldiazabutadiene complexes and their self-assembly into infinite 1-dimensional chains in the solid state via rare C (sp2)–H … Hal hydrogen bonding is reported. All the new compounds were characterized using elemental analyses (C, H, N), ESI-MS, IR, 1H and 13C NMR techniques and X-ray diffraction analysis. The nature and energies of intermolecular non-covalent interactions, which are responsible for the supramolecular polymerization, were studied theoretically using DFT calculations and topological analysis of the electron density distribution within the formalism of Bader's theory (QTAIM method). While chloro-complexes, which feature a relatively stronger C (sp2)–H … Hal hydrogen bonding, form supramolecular polymers, the iodo-derivative does not self-assemble into 1-D chains due to the dominance of other crystal packing forces over the potential H⋯I contacts. Thus, the C (sp2)–H … Hal HB can dictate a packing preference in the solid state and serve as a useful tool for supramolecular engineers.

Effect of screw profile and processing conditions on physical transformation and chemical degradation of gabapentin during twin-screw melt granulation

Twin-screw melt granulation (TSMG) was applied to process a powder blend consisting of 80% gabapentin (GABA) and 20% hydroxypropyl cellulose. The effect of screw profile and processing conditions on the process-induced transformation and chemical degradation of gabapentin was studied. When a neutral kneading block was used, gabapentin underwent polymorphic transformation. A forward kneading block in combination with processing under torque conditions was required to minimize chemical degradation and to inhibit polymorphic transformation of gabapentin. Both the size of the extruded granules and gabapentin degradant level correlated positively with the specific rate, the ratio between feed rate and screw speed. At higher specific rate, the barrel was filled to a greater extent. The material packing and compressive forces were enhanced, as proven by the increased rupturing of CAMES® sensor beads and GABA crystal size reduction. This resulted in more interaction between the powder particles and facilitated granule growth. Simultaneously, this also resulted in higher degradant level. To attain adequate tabletability, the specific rate must reach a threshold value. The development of an optimum TSMG process requires balancing processing parameters based on the physical and chemical stability of GABA as well as its tabletability.

Predicting Supramolecular Connectivity of Metal-Containing Solid-State Assemblies using Calculated Molecular Electrostatic Potential Surfaces

We demonstrated that the primary supramolecular features of metal-based solid-state systems can be reliably predicted based solely on the relative strengths of competing hydrogen-bond acceptor sites. The predictive protocol utilizes a simple electrostatic view of the hydrogen bond and ranks the multiple acceptor sites according to calculated molecular electrostatic potential (MEP) surface values. The MEP was calculated for competing acceptors on 12 zero-dimensional (0-D) 2, 4-pentanedionate (acac)-based complexes (Ni(II), Co(II), Cu(II)), equipped with the lactam moiety, and the structural outcome was successfully predicted in 10 of 12 compounds by comparing the MEP difference between two acceptors, namely, the lactam and acac-based oxygen atoms. The two acceptor sites displayed structural selectivity as long as there was a substantial difference (ΔE > ΔEcutoff) between their relative hydrogen-bond acceptor capabilities. In the remaining two cases, the expected coordination geometry around the metal center did not materialize, which meant that a prediction of the supramolecular details could not be done. The working cutoff value (ΔEcutoff ≈ 30 kJ/mol) proved to be a valid and decisive criterion for predicting the supramolecular connectivity in these 0-D systems. The results further indicate that the ΔEcutoff is likely to be primarily dependent on the supramolecular functionality itself rather than on external “packing forces”.

Unveiling the n\u2192\u03c0* interactions in dipeptides

Numerous studies have suggested that the n→π* interactions between carbonyls could contribute significantly to the stability of proteins. Nevertheless, their evaluation is challenging because of the solvent environment or crystal packing forces in solids. Here we study the rotational spectrum of HGlyProOH dipeptide, a very common sequence found in collagen, the most abundant protein in vertebrates, in isolated conditions. Three different structures are unequivocally characterized in the gas phase. Interestingly, the most abundant structure is stabilized by an n→π* interaction and adopts the same conformation as is found in crystalline collagen. This observation serves to support the importance of the n→π* interactions between carbonyl groups.

Progress Toward a Semi-Synthetic Organism with an Unrestricted Expanded Genetic Alphabet.

We have developed a family of unnatural base pairs (UBPs), exemplified by the pair formed between dNaM and dTPT3, for which pairing is mediated not by complementary hydrogen bonding but by hydrophobic and packing forces. These UBPs enabled the creation of the first semisynthetic organisms (SSOs) that store increased genetic information and use it to produce proteins containing noncanonical amino acids. However, retention of the UBPs was poor in some sequence contexts. Here, to optimize the SSO, we synthesize two novel benzothiophene-based dNaM analogs, dPTMO and dMTMO, and characterize the corresponding UBPs, dPTMO-dTPT3 and dMTMO-dTPT3. We demonstrate that these UBPs perform similarly to, or slightly worse than, dNaM-dTPT3 in vitro. However, in the in vivo environment of an SSO, retention of dMTMO-dTPT3, and especially dPTMO-dTPT3, is significantly higher than that of dNaM-dTPT3. This more optimal in vivo retention results from better replication, as opposed to more efficient import of the requisite unnatural nucleoside triphosphates. Modeling studies suggest that the more optimal replication results from specific internucleobase interactions mediated by the thiophene sulfur atoms. Finally, we show that dMTMO and dPTMO efficiently template the transcription of RNA containing TPT3 and that their improved retention in DNA results in more efficient production of proteins with noncanonical amino acids. This is the first instance of using performance within the SSO as part of the UBP evaluation and optimization process. From a general perspective, the results demonstrate the importance of evaluating synthetic biology "parts" in their in vivo context and further demonstrate the ability of hydrophobic and packing interactions to replace the complementary hydrogen bonding that underlies the replication of natural base pairs. From a more practical perspective, the identification of dMTMO-dTPT3 and especially dPTMO-dTPT3 represents significant progress toward the development of SSOs with an unrestricted ability to store and retrieve increased information.

Influence of particle packing structure on sound velocity**Project supported by the National Natural Science Foundation of China (Grant No. 11547009), the Young Scientists Fund of the National Natural Science Foundation of China (Grant No. 11602062), the Natural Science Foundation of Guizhou Province, China (Grant No. 2012/2166), and the Research Foundation of Guizhou University for Talent Introduction, China (Grant No. 2011/02).

The anisotropy in the particle systems of different packing structures affects the sound velocity. The acoustic propagation process in four kinds of packing structures (denoted as S45, H60, S90, and D) of two-dimensional granular system is simulated by the discrete element method. The velocity vtof obtained by the time of flight method and the velocity vc obtained from the stiffness tensor of the system are compared. Different sound velocities reflect various packing structures and force distributions within the system. The compression wave velocities of H60 and S90 are nearly the same, and transmit faster than that of D packing structure, while the sound velocity of S45 is the smallest. The shear wave velocities of S45 and H60 are nearly the same, and transmit faster than that of D packing structure. The compression wave velocity is sensitive to the volume fraction of the structure, however, the shear wave velocity is more sensitive to the geometrical structure itself. As the normal stress p is larger than 1 MPa, vtof and vc are almost equal, and the stiffness tensors of various structures explain the difference of sound velocities. When the normal stress is less than 1 MPa, with the coordination number unchanged, the law vtof ∝ p1/4 still exists. This demonstrates that apart from different power laws between force and deformation as well as the change of the coordination number under different stresses, there are other complicated causes of vtof ∝ p1/4, and an explanation of the deviation from vtof ∝ p1/6 is given from the perspective of dissipation.

Tetrathiafulvalene Dimer Merged with a Binuclear Ring of Sn and Sb: Synthesis and Molecular Structures Induced by Heteroatoms

In this study, we describe the synthesis and characterization of dimeric tetrathiafulvalene (TTF) derivatives that are doubly bridged by Sn (1) and Sb (2a) atoms as a new class of organic‐inorganic hybrid compounds able to provide enhanced dimensionality in the solid state. The antimony heterocyclic framework was constructed by a simple Sn–Sb metal exchange reaction of a 1,4‐distannine moiety with p‐tolyl antimony dichloride (p‐tolSbCl2). Compound 2a was obtained in cis and trans forms as a stable configurational isomer. From X‐ray crystallographic analysis, there were three conformational isomers in which the tolyl rings were directed in the endo or exo direction. Crystal packing revealed a supramolecular three‐dimensional network through intermolecular short contacts of Sb···S and Sb···π. These packing forces gave a trans‐2aexo–exo conformation in the crystal, although the theoretical calculations predict its instability compared with other conformers. Cyclic voltammetry (CV) measurements of 1 and cis/trans‐2a revealed two pairs of reversible redox processes corresponding to the formation of TTF/TTF·+ and TTF·+/TTF2+. Furthermore, CV of cis/trans‐2a also revealed the reduction waves derived from the reduction of SbIII. Dicationic and tetracationic species were prepared by chemical oxidation, and their electronic structures were also investigated by electronic spectroscopy.

London Dispersion Forces in Crystal Packing of Thiourea Derivatives

Novel thioureas RNHC(S)NHP(S)(OiPr)2 [R = (HOCH2)(Me)2C (1), Me2CH2CH2 (2), 2-CF3C6H4 (3), 2-Pym (4), and bis-thiourea 1,5-C10H6{NHC(S)NHP(S)(OiPr)2} (5)] have been synthesized and characterized by NMR, X-ray diffraction, Hirshfeld surface analysis, and theoretical ETS-NOCV charge and energy decomposition calculations. The monomers contain multiple intramolecular noncovalent interactions including N–H···X (X = O, 1–3; F, 3; N, 4; S, 5) and C–H···Y (Y = O, 1; N, 2 and 3; S, 4 and 5) augmented further by homopolar C–H···H–C contacts in all the structures. It has been determined that the three-dimensional crystal networks are primarily constituted from intermolecular H···H and H···S contacts due to homopolar C–H···H–C as well as X–H···S (X = N, C) interactions. They are, depending on the system, augmented further by C–H···Y (Y = π, S, F) as well as by σ-hole(S)···π interactions. ETS-NOCV allowed us to delineate that in the case of C–H···H–C, C–H···Y, and σ-hole(S)···π intermolecular interactions, except for ...

Poly[(μ5-cis-cyclohex-4-ene-1,2-dicarboxylato)(μ3-cis-cyclohex-4-ene-1,2-dicarboxylato)dicadmium(II)

The title compound, [Cd2(C8H8O4)2] n , crystallizes in the centrosymmetric monoclinic P21/n space group. Via cis-cyclohex-4-ene-1,2-dicarboxylate ligands in two different binding modes, square pyramidally and pentagonal bipyramidally coordinated Cd atoms are connected into coordination polymer layer motifs oriented parallel to the ab plane. These layered motifs are aggregated into the three-dimensional supramolecular crystal structure of the title compound by means of crystal packing forces.

Poly(ethylene glycol) diacrylate as a novel chaotropic compound for design of aqueous biphasic systems

In this work novel solvent, poly(ethylene glycol) diacrylate (PEGDA) of average number molecular weight 700, is proposed for design of aqueous biphasic systems with salting-out agents: K3PO4/Na3C6H5O7/K2CO3/MnSO4/Li2SO4/ZnSO4. Ternary liquid-liquid equilibrium experiments were conducted at constant temperature 298.15K and 0.1MPa, where binodal curves and tie-lines were determined. The consistency of equilibrium data were checked and confirmed using Othmer-Tobias and Bancroft equations. Density ρ, viscosity η and refractive index nD have been experimentally measured for PEGDA 700+water system over the temperature range T=(293.15 to 323.15) K with temperature step 5K and at atmospheric pressure. Excess molar volumes VE, viscosity deviations Δη, deviations in refractive index ΔnD, excess Gibbs free energy of activation of viscous flow ∆G⁎E, partial molar volumes V¯i, excess partial molar volumes V¯iE and it's values at infinite dilutions V¯iE,∞ were calculated from experimental data and used to analyze non-ideal behavior of polymer aqueous solution. Fourier-transform infrared analysis (FT-IR) of PEGDA+water mixture and corresponding pure components was performed at T=298.15K in order to gain insight into the molecular structure of the mixture. FT-IR analysis indicates the absence of hydrogen bonding between PEGDA 700 and water. This leads to the conclusion that non-ideal behavior of mixture is contributed to geometrical packing or van der Waals forces of different species.

1-Deoxy-1-(N-methyl-4-fluorophenylamino)-D-arabino-hexulose

The title compound, C13H18FNO5, consists of D-fructose with an aromatic amine. The carbohydrate chain is in the acyclic keto form and has the zigzag conformation, while the solid-state NMR data suggests a conformational dimorphism at the aromatic amine group. The carbohydrate portion is involved in extensive O—H...O hydrogen bonding, which forms a two-dimensional network parallel to (001) and organized into fused homodromic ring patterns. The Hirshfeld surface fingerprint plots reveal a major contribution of the non-polar H...H and C...H interactions to the crystal packing forces.

Highly Nonplanar Macrocyclic Ring Conformation in the Crystal Structures of Ni(II) And Cu(II) Octaphenylporphyrins

Crystal structures of solvated highly nonplanar nickel(II) and copper(II) complexes of 2,3,5,10,12,13,15,20- octaphenylporphyrin are determined by single crystal XRD analysis. The macrocycles in these systems exhibit mainly ruffled and saddled conformations. The average displacement of the pyrrole carbon atom ΔCb from the mean plane of the porphyrin ring is as high as ±0.70 A. The Hirshfeld surface analysis of both structures reveals mainly H…H (57-59%) intermolecular short contacts with a smaller contribution from C…H (16-22%) and H…Cl (11-19%) interactions. The present work suggests that the nonplanarity of the macrocycle in NiTPP(Ph)4 is largely due to the core Ni(II) ion and less influenced by intermolecular interactions/crystal packing forces, whereas the opposite is true in the case of the nonplanar CuTPP(Ph)4 structure.

Structural, spectroscopic and docking properties of resorcinol, its -OD isotopomer and dianion derivative: a comparative study

Structural and vibrational properties of resorcinol, its -OD isotopomer and dianion salt were compared with the help of quantum-chemical and spectroscopic techniques. The relative stability computed at the MP4/6-311++G(d,p) level predicted that the syn-syn rotameric form of the resorcinol molecule is about 0.7 kcal/mol higher in energy than the more stable anti-syn and anti-anti forms. Vibrational frequencies calculated for the optimized α-resorcinol and its -OD isotopomer unit cells showed that out-of-plane bending vibrations tend to shift to higher wavenumbers for the solid phase compared to the non-condensed phase indicating strong intermolecular packing forces. OH/OD isotopic shifts were identified for stretching and binding modes, which supported by DFT findings. Infrared, Raman and proton NMR data confirmed a notable change in the overall electronic properties of resorcinol upon the abstraction of the hydroxyl protons. In addition, resorcinol, in its three rotameric configurations, exhibited a stable complexation with keratin-7. While the highly electronegative nature of oxygen atoms contributed effectively to the binding affinity of resorcinol towards keratin-7, careful docking analysis showed that the steric factor play the major role in the keratolytic activity of resorcinol.

Molecular and crystal structure and the Hirshfeld surface analysis of 1-amino-1-deoxy-α-d-sorbopyranose and 1-amino-1-deoxy-α-d-psicopyranose (“d-sorbosamine” and “d-psicosamine”) derivatives

Sorbosamine and psicosamine are the last two 1-amino-1-deoxy-hexuloses for which no structural data were available. We report on a13C NMR and a single crystal X-ray diffraction study of 1-deoxy-1-(N-methylphenylamino)-d-sorbose (1) and 1-deoxy-1-(N-methylphenylamino)-d-psicose (2). In solutions, both aminosugars are conformationally unstable and establish equilibria, with 90.7% α-pyranose, 3.8% α-furanose, 1.0% β-pyranose, 0.5% β-furanose, and 4.0% acyclic keto form for 1 and 32.4% α-furanose, 27.2% α-pyranose, 21.0% β-pyranose, 9.1% β-furanose, and 11.0% acyclic keto form for 2. X-ray diffraction data provided detailed structural information on 1 and 2 in the α-pyranose form. Both molecules adopt the 5C2 ring conformations, the bond distances and valence angles compare well with respective pyranose structures. All hydroxyl groups in crystal structures of both 1 and 2 participate in two-dimensional hydrogen bonding networks, the H-bonding pattern in 1 is dominated by co-crystallized water molecules. The Hirshfeld surface analysis revealed a significant contribution of non- or weakly polar interactions to the packing forces for both molecules, with crystal structure of 2 featuring short H⋯H contacts. Other structural features found in 2 are a significant planarity of the tertiary amino group (the pyramid heights are 0.127 Å in 2 vs 0.231 Å in 1), a concomitant non-involvement of the amine nitrogen in heteroatom contacts, and a unique anti-periplanar conformation around the C1C2 bond.