Interconversion Barrier Research Articles

‘Invisible’ Molecular Dynamics Revealed for a Conformationally Chiral π‐Stacked Perylene Bisimide Foldamer

Whilst energetic and kinetic aspects of folding processes are meanwhile well understood for natural biomacromolecules, the folding dynamics in so far studied artificial foldamer counterparts remain largely unexplored. This is due to the low energy barriers between their conformational isomers that make the dynamic processes undetectable with conventional methods such as UV/vis absorption, fluorescence, and NMR spectroscopy, making such processes ‘invisible’. Here we present an asymmetric perylene bisimide dimer (bis‐PBI 1) that possesses conformational chirality in its folded state. Owing to the large interconversion barrier (≥ 116 kJ mol–1), four stereoisomers could be separated and isolated. Since the interconversion between these stereoisomers requires the foldamer to first open and then to re‐fold, the transformation of one stereoisomer into others allowed us to ‘visualize’ the dynamics of folding with time and determine its lifetimes and the energetic barriers associated with the folding process. Supported by quantum chemical calculations, we identified the open structure to be only a fleeting metastable state of higher energy. Our experimental observation of the kinetics associated with the molecular dynamics in the PBI foldamer advances the fundamental understanding of folding in synthetic foldamers and paves the way for the design of smart functional materials.

'Invisible' Molecular Dynamics Revealed for a Conformationally Chiral π-Stacked Perylene Bisimide Foldamer.

Whilst energetic and kinetic aspects of folding processes are meanwhile well understood for natural biomacromolecules, the folding dynamics in so far studied artificial foldamer counterparts remain largely unexplored. This is due to the low energy barriers between their conformational isomers that make the dynamic processes undetectable with conventional methods such as UV/vis absorption, fluorescence, and NMR spectroscopy, making such processes 'invisible'. Here we present an asymmetric perylene bisimide dimer (bis-PBI 1) that possesses conformational chirality in its folded state. Owing to the large interconversion barrier (≥ 116 kJ mol-1), four stereoisomers could be separated and isolated. Since the interconversion between these stereoisomers requires the foldamer to first open and then to re-fold, the transformation of one stereoisomer into others allowed us to 'visualize' the dynamics of folding with time and determine its lifetimes and the energetic barriers associated with the folding process. Supported by quantum chemical calculations, we identified the open structure to be only a fleeting metastable state of higher energy. Our experimental observation of the kinetics associated with the molecular dynamics in the PBI foldamer advances the fundamental understanding of folding in synthetic foldamers and paves the way for the design of smart functional materials.

C(P)42+: a viable planar tetracoordinate carbon species.

Tetrahedral carbon is a well-accepted structural motif. Theory has paved the way for many rule-breaking planar tetracoordinate carbon structures. Herein, we have explored the possibility of phosphorous supported carbon cluster C(P4)2+ to locate a planar tetracoordinate carbon centre (ptC). Our calculations revealed a penta-atomic planar tetracoordinate carbon (ptC) atom as a local minimum with a significant barrier for interconversion into the lowest energy isomer. The proposed species is kinetically stable and is a probable candidate for experimental detection. The stabilization of the planar structure arises due to delocalization of the p-electrons of the central carbon atom to the surrounding P4 skeleton and significant electrostatic attraction.

Vibrational spectroscopy and dissociation dynamics of cyclohexyl hydroperoxide.

Organic hydroperoxides (ROOH) are ubiquitous in the atmospheric oxidation of volatile organic compounds (VOCs) as well as in low-temperature oxidation of hydrocarbon fuels. The present work focuses on a prototypical cyclic hydroperoxide, cyclohexyl hydroperoxide (CHHP). The overtone OH stretch (2νOH) spectrum of jet-cooled CHHP is recorded by IR multiphoton excitation with UV laser-induced fluorescence detection of the resulting OH products. A distinctive IR feature is observed at 7012.5 cm-1. Two conformers of CHHP are predicted to have similar stabilities (within 0.2 kcal mol-1) and overtone OH stretch transitions (2νOH), yet are separated by a significant interconversion barrier. The IR power dependence indicates that absorption of three or more IR photons is required for dissociation of CHHP to cyclohexoxy (RO) and OH radical products. Accompanying high-level single- and multi-reference electronic structure calculations quantitatively support the experimental results. Calculations are extended to a range of organic hydroperoxides to examine trends in bond dissociation energies associated with RO + OH formation and compared with prior theoretical results.

Controlling achiral and chiral conformations of benzyl alcohol by ortho-halogenation, collisional relaxation and dimerisation.

Ortho-Halogenated benzyl alcohol can exist in two different low energy chiral conformations, only one of them with an OH-X contact (X = Cl, Br, I). A third, achiral conformation is enabled by the halogen substitution. We show by IR spectroscopy in supersonic jets that the achiral monomer is less stable than the chiral conformation with OH-X contact, but both can be produced in similar amounts using helium as a carrier gas. The robust OH transition observed for the achiral monomer is a sensitive benchmark for the conformational energy sequence, since the chiral conformation without OH-X contact is at least an order of magnitude less abundant, although it is often predicted by DFT to be slightly more stable and separated from the achiral conformation by a low barrier. This competing chiral conformation must be energetically higher by at least a few tenths of a kJ mol-1 to be consistent with experimental observations. That is indeed predicted by high-level energy calculations at the DFT-optimised structures. The most stable dimers of ortho-halogenated benzyl alcohols involve torsionally homo- and heterochiral pairings of the two OH groups, where the hydrogen bond-accepting OH group forms a cooperative intramolecular OH-X contact. The achiral monomer conformation is suppressed in these dimers. A homochiral dimer is formed almost exclusively for Cl, whereas its heterochiral variant is progressively co-stabilised with increasing halogen size. The stretching wavenumber of the donor OH in the dimers depends on the relative chirality of the donor and acceptor conformations. The consistent picture that emerges for Cl, Br and I substitution in ortho-position of benzyl alcohol is discussed in the context of interconversion barriers, heavy atom tunneling, π-π stacking, suppression of OH-π bonding, chirality synchronisation, and shortcomings of DFT approaches in reproducing the observations. The homochiral aggregation preference observed for simple benzyl alcohol is conserved and even enhanced upon ortho-halogenation, albeit partly by different interactions.

High-resolution infrared spectroscopy of jet cooled cyclobutyl in the α-CH stretch region: large-amplitude puckering dynamics in a 4-membered ring radical.

Gas-phase cyclobutyl radical (c-C4H7) is generated at a rotational temperature of Trot = 26(1) K in a slit-jet discharge mixture of 70% Ne/30% He and 0.5-0.6% cyclobromobutane (c-C4H7Br). A fully rovibrationally resolved absorption spectrum of the α-CH stretch fundamental band between 3062.9 cm-1 to 3075.7 cm-1 is obtained and analyzed, yielding first precision structural and dynamical information for this novel radical species. The α-CH stretch band origin is determined to be 3068.7887(4) cm-1, which implies only a modest (≈0.8 cm-1) blue shift from rotationally unresolved infrared spectroscopic studies of cyclobutyl radicals in liquid He droplets [A. R. Brown, P. R. Franke and G. E. Douberly, J. Phys. Chem. A, 2017, 121, 7576-7587]. Of particular dynamical interest, a one-dimensional potential energy surface with respect to the ring puckering coordinate is computed at CCSD(T)/ANO2 level of theory and reveals a double minimum Cs puckered geometry, separated by an exceedingly shallow planar C2v transition state barrier (Ebarr ≈ 1 cm-1). Numerical solutions on this double minimum potential yield a zero-point energy for the ground state (Ezero-point ≈ 27 cm-1) greatly in excess of the interconversion barrier. This is indicative of highly delocalized, large amplitude motion of the four-membered ring structure, for which proper vibrationally averaging of the moment of inertia tensor reproduces the experimentally determined inertial defect remarkably well. Finally, intensity alternation in the experimental spectrum due to nuclear spin statistics upon exchange of three indistinguishable H atom pairs (IH = ½) matches Ka + Kc = even : odd = 36 : 28 predictions, implying that the unpaired electron in the radical center lies in an out-of-plane pπ orbital. Thus, high-resolution infrared spectroscopy provides first experimental confirmation of a shallow double minimum ring puckering potential with a highly delocalized ground state wave function peaked at a planar C2v transition state geometry consistent with a cyclobutyl π radical.

Forcing Twisted 1,7‐Dibromoperylene Diimides to Flatten in the Solid State: What a Difference an Atom Makes

AbstractPerylene diimides (PDI) are workhorses in the field of organic electronics, owing to their appealing n‐semiconducting properties. Optimization of their performances is widely pursued by bay‐atom substitution and diverse imide functionalization. Bulk solids and thin‐films of these species crystallize in a variety of stacking configurations, depending on the geometry of the stable conformation of the polyaromatic core. We here demonstrate that 1,7‐dibromo‐substituted perylene diimides, PDI(H2Br2), possessing a heavily twisted conformation in the gas phase, in solution and in the solids, can be easily flattened in the solid state into centrosymmetric molecules if the polyaromatic cores form π–π stabilized chains. This is achieved by using axial residues with low stereochemical hindrance, as guaranteed by a single CH2/NH spacer directly linked to the imide function. Structural powder diffraction and DFT calculations on four newly designed species of the PDI(H2Br2) class coherently show that, thanks to the flexibility of the N−X−Ar link (X=CH2/NH), flat cores are indeed obtained by overcoming the interconversion barrier between twisted atropoisomers, of only 26.5 kJ mol−1. This strategy may then be useful to induce “anomalously flat” polyaromatic cores of different kinds (substituted acenes/rylenes) in the solid state, towards suitable crystal packing and orbital interactions for improved electronic performances.

Forcing Twisted 1,7-Dibromoperylene Diimides to Flatten in the Solid State: What a Difference an Atom Makes.

Perylene diimides (PDI) are workhorses in the field of organic electronics, owing to their appealing n-semiconducting properties. Optimization of their performances is widely pursued by bay-atom substitution and diverse imide functionalization. Bulk solids and thin-films of these species crystallize in a variety of stacking configurations, depending on the geometry of the stable conformation of the polyaromatic core. We here demonstrate that 1,7-dibromo-substituted perylene diimides, PDI(H2 Br2 ), possessing a heavily twisted conformation in the gas phase, in solution and in the solids, can be easily flattened in the solid state into centrosymmetric molecules if the polyaromatic cores form π-π stabilized chains. This is achieved by using axial residues with low stereochemical hindrance, as guaranteed by a single CH2 /NH spacer directly linked to the imide function. Structural powder diffraction and DFT calculations on four newly designed species of the PDI(H2 Br2 ) class coherently show that, thanks to the flexibility of the N-X-Ar link (X=CH2 /NH), flat cores are indeed obtained by overcoming the interconversion barrier between twisted atropoisomers, of only 26.5 kJ mol-1 . This strategy may then be useful to induce "anomalously flat" polyaromatic cores of different kinds (substituted acenes/rylenes) in the solid state, towards suitable crystal packing and orbital interactions for improved electronic performances.

Cycloaddition and C-S Bond Cleavage Processes in Reactions of Heterometallic Phosphinidene-Bridged MoRe and MoMn Complexes with Alkynes and Phenyl Isothiocyanate.

Reactions of [MoReCp(μ-PMes*)(CO)6] with internal alkynes RC≡CR yielded the phosphapropenylidene-bridged complexes [MoReCp(μ-κ2P,C:η3-PMes*CRCR)(CO)5] (Mes* = 2,4,6-C6H2tBu3; R = CO2Me, Ph). Terminal alkynes HC≡CR1 gave mixtures of isomers [MoReCp(μ-κ2P,C:η3-PMes*CHCR1)(CO)5] and [MoReCp(μ-κ2P,C:η3-PMes*CR1CH)(CO)5], with the first isomer being major (R1 = CO2Me) or unique (R1 = tBu), indicating the relevance of steric repulsions during the [2 + 2] cycloaddition step between Mo=P and C≡C bonds in these reactions. Similar reactions were observed for [MoMnCp(μ-PMes*)(CO)6]. Addition of ligands to these complexes promoted rearrangement of the phosphapropenylidene ligand into the allyl-like μ-η3:κ1C mode, as shown by the reaction of [MoReCp(μ-κ2P,C:η3-PMes*CHC(CO2Me)}(CO)5] with CN(p-C6H4OMe) to give [MoReCp{μ-η3:κ1C-PMes*CHC(CO2Me)}(CO)5{CN(p-CH4OMe)}2]. The MoRe phosphinidene complex reacted with S=C=NPh to give as major products the phosphametallacyclic complex [MoReCp{μ-κ2P,S:κ2P,S-PMes*C(NPh)S}(CO)5] and its thiophosphinidene-bridged isomer [MoReCp(μ-η2:κ1S-SPMes*)(CO)5(CNPh)]. The first product follows from a [2 + 2] cycloaddition between Mo=P and C=S bonds, with specific formation of P-C bonds, whereas the second one would arise from the alternative cycloaddition involving the formation of P-S bonds, more favored on steric grounds. The prevalence of the μ-η2:κ1S coordination mode of the SPMes* ligand over the μ-η2:κ1p mode was investigated theoretically to conclude that steric congestion favors the first mode, while the kinetic barrier for interconversion between isomers is low in any case.

A Buckycatcher in Solution-A Computational Perspective.

In this work, we study the buckycatcher (C60H28) in solution using quantum chemical models. We investigate the conformational equilibria in several media and the effects that molecules of solvent might have in interconversion barriers between the different conformers. These are studied in a hypothetical gas phase, in the dielectric of a solvent, as well as with hybrid solvation. In the latter case, due to a disruption of π-stacking interactions, the transition states are destabilized. We also evaluate the complexation of the buckycatcher with solvent-like molecules. In most cases studied, there should be no adducts formed because the enthalpy driving force cannot overcome entropic penalties.

Inducing transient enantiomeric excess in a molecular quantum racemic mixture with microwave fields

Chiral molecules with low enantiomer interconversion barriers racemize even at cryogenic temperatures due to quantum tunneling, forming a racemic mixture that is impossible to separate using conventional chemical methods. Here we both experimentally and theoretically demonstrate a method to create and probe a state-specific enantiomeric enrichment for such molecular systems. The coherent, non-linear, and resonant approach is based on a microwave six-wave mixing scheme and consists of five phase-controlled microwave pulses. The first three pulses induce a chiral wavepacket in a chosen rotational state, while the consecutive two pulses induce a polarization for a particular rotational transition (listen transition) with a magnitude proportional to the enantiomeric excess created. The experiments are performed with the transiently chiral molecule benzyl alcohol, where a chiral molecular response was successfully obtained. This signal demonstrates that enantiomeric excess can be induced in a quantum racemic mixture of a transiently chiral molecule using the developed microwave six-wave mixing scheme, which is an important step towards controlling non-rigid chiral molecular systems.

Raising the benchmark potential of a simple alcohol-ketone intermolecular balance.

2-Butanone offers two hydrogen bond docking variants to a solvating methanol which are cleanly separated by supersonic jet infrared absorption spectroscopy in the OH-stretching range, resolving earlier action spectroscopy indeterminacies for this elementary case of an intermolecular alcohol-ketone balance. The solvent preference for the shorter chain side is unambiguously derived from the spectra of homologous compounds. It is analysed in terms of competing steric and dispersion interactions and the resulting energy differences across a low interconversion barrier. Fortuitous cancellations are discussed and quantitative energy deficiencies of the employed DFT approaches are suggested. Some benchmarkable experimental observations: at low temperature, a single methanol molecule prefers the methyl-sided oxygen lone pair of 2-butanone over the ethyl-sided lone pair by 1-2 kJ mol-1, the trans butane backbone is conserved in both low-lying isomers, the OH-stretching fundamentals differ by 47(2) cm-1.

Competing C-4 and C-5-Acyl Stabilization of Uronic Acid Glycosyl Cations.

Uronic acids are carbohydrates carrying a terminal carboxylic acid and have a unique reactivity in stereoselective glycosylation reactions. Herein, the competing intramolecular stabilization of uronic acid cations by the C-5 carboxylic acid or the C-4 acetyl group was studied with infrared ion spectroscopy (IRIS). IRIS reveals that a mixture of bridged ions is formed, in which the mixture is driven towards the C-1,C-5 dioxolanium ion when the C-5,C-2-relationship is cis, and towards the formation of the C-1,C-4 dioxepanium ion when this relation is trans. Isomer-population analysis and interconversion barrier computations show that the two bridged structures are not in dynamic equilibrium and that their ratio parallels the density functional theory computed stability of the structures. These studies reveal how the intrinsic interplay of the different functional groups influences the formation of the different regioisomeric products.

CH4·F− revisited: full-dimensional ab initio potential energy surface and variational vibrational states

ABSTRACT The automated development of a new ab initio full-dimensional potential energy surface (PES) is reported for the CH4·F− complex using the Robosurfer program package. The new potential provides a near-spectroscopic quality description over a broad configuration range including the methane-ion dissociation, as well as isolated methane vibrations. In particular, it improves upon the earlier [Czakó, Braams, Bowman (2008)] PES over intermediate methane-fluoride distances. Full-dimensional (12D) variational vibrational computations using the new PES and the GENIUSH-Smolyak algorithm show that tunnelling splittings larger than 0.1 cm−1 appear below the top of the interconversion barrier of the four equivalent minima of the complex.

Heptagon-Embedded π-Expanded Thieno- and N-Methylpyrrolo-Pyridazines with Substantial Out-of-Plane Dipole Moment.

Herein, we describe the synthesis and characterization of fully fused tetraphenylthieno[3,4-d]pyridazine 1 and N-methylpyrrolo[3,4-d]pyridazine 2 with two embedded seven-membered rings. Owing to the incorporated heptagon, 1 and 2 exhibited Cs-symmetric saddle conformations in the solid state with mean plane deviation around 0.38 Å. π-Expanded thienopyridazine 1 showed a one-dimensional (1-D) columnar packing along the b axis with net dipole moment aligning perpendicular to the b axis in the polar crystal system Pc. On the other hand, 2 formed a partially π-stacked brick-work structure. In addition to the Cs-symmetric saddle conformations found in the crystals, density functional theory (DFT) calculation found C2-symmetric twisted conformations of both 1 and 2 close in energy to the saddle conformations. The barrier of conformational interconversion was calculated to be 32 (1) and 31 kJ·mol-1 (2), and the interconversion occurs fast even at -60 °C as evidenced by variable-temperature (VT)-NMR studies. While 1 and 2 have moderately curved structures, optical and electrochemical studies revealed effective π-conjugation over the fused diphenylene units, which is also supported by DFT calculation. As the result of the intrinsic large dipole moment of thieno- and pyrrolo-pyridazines and the notably curved structure, 1 (2) has a substantial out-of-plane dipole moment of 2.0 (3.3) D in the saddle conformations.

Tautomerism of cytosine, cytidine, and deoxycytidine: Proton transfer through water bridges

AbstractAltogether six tautomers of cytosine and three tautomers of cytidine and deoxycytidine are studied theoretically in the gas phase and in a microhydrated environment. Their structures are optimized at MP2/6–31 + G(d,p) level. The relative energies of the isolated and the hydrated tautomers included the correction to higher correlation energy terms evaluated at the SCS‐MP2, MP4, and CCSD(T) levels. The free energies at 298 K and higher temperatures are based on the above‐mentioned relative energies and temperature‐dependent enthalpy terms and entropies evaluated at the MP2/6–31 + G(d,p) level. Theoretical predictions for the coexistence of five species for cytosine in the gas phase (canonical, trans‐ and cis‐enol‐amino, trans‐ and cis‐imino‐oxo forms) fully agree with recent experimental results. Five‐hydrated cytosine tautomeric forms of are investigated at CPCM/SCS‐MP2/6–31 + G(d,p) level to evaluate the interconversion barriers between them and to explain the coexistence, experimentally proven, of two amino‐oxo and one imino‐oxo tautomers of cytosine in aqueous solution. The presence of coordinated water molecules acting as a catalyst make the tautomerization processes quite easier. It appeared clear from the obtained data that the influence of the hydrogen‐bonded water molecules as well as the introduction of solvent effects in reducing the height of the tautomerization barriers for these five‐hydrated systems is quite substantial. Similar results are obtained for the tri‐hydrated cytidine and the 2‐deoxycytidine tautomeric forms. In aqueous solution of cytidine, syn‐ and syn‐clinal‐conformers оf the amino‐oxo tautomer should coexist with small amounts of syn‐ and syn‐clinal conformers оf imino‐oxo tautomer. For 2‐deoxycytidine an equilibrium has been found to exist between the syn‐ and anti‐conformers of the amino‐oxo and the imino‐oxo tautomers. The water‐assisted proton transfer reactions released through asynchronous concerted mechanism and the conformation of the sugar ring in nucleosides does not change during the tautomerization.

Conformational landscape and internal dynamics of limona ketone, a key oxidation product of limonene

The rotational spectrum of limona ketone (4-acetyl-1-methyl-1-cyclohexene), a key oxidation product of limonene, was recorded in the gas phase using a Fourier transform microwave spectrometer coupled to a supersonic jet expansion over the 4–20 GHz range. To display a complete view of the conformational landscape of this relatively flexible system, the relative stability and inter-conversion barriers between conformers were explored by electronic structure calculations. The lowest energy equatorial conformer was detected, and its spectroscopic molecular parameters were determined from the analysis of the spectrum. The internal rotation of the methyl group attached to the aldehyde moiety was taken into account in the analysis. The internal dynamics of the methyl group within the acetyl moiety was quantitatively described. Experimental lines of both A and E symmetry were fitted to experimental accuracy, and the experimental barrier height of the methyl group internal rotation is discussed with the support of quantum chemical calculations.

Spectroscopic and theoretical study of the intramolecular π-type hydrogen bonding and conformations of 3-cyclohexen-1-ol

The conformations of 3-cyclohexen-1-ol (3CHOL) have been investigated by MP2/cc-pVTZ and CCSD/cc-pVTZ ab initio computations and by infrared spectroscopy. The six conformational minima correspond to specific values of the ring-twisting and OH internal rotation coordinates. The map of a two-dimensional potential energy surface (PES) that governs the conformational dynamics along the ring-twisting and the OH group internal rotation coordinates was generated. The relative energies of the conformational minima and the interconversion barriers for the ring twisting and internal rotations were computed. According to the MP2/cc-pVTZ computations, the conformer with intramolecular π-type hydrogen bonding has the lowest calculated energy by 108 cm−1. However, according to the CCSD/cc-pVTZ computations this conformer a tiny 10 cm−1 higher in energy than one without hydrogen bonding. The infrared spectrum in the OH stretching region agrees well with the predicted frequency differences between the conformers.

Chiral photochemistry of achiral molecules

Chirality is a molecular property governed by the topography of the potential energy surface (PES). Thermally achiral molecules interconvert rapidly when the interconversion barrier between the two enantiomers is comparable to or lower than the thermal energy, in contrast to thermally stable chiral configurations. In principle, a change in the PES topography on the excited electronic state may diminish interconversion, leading to electronically prochiral molecules that can be converted from achiral to chiral by electronic excitation. Here we report that this is the case for two prototypical examples – cis-stilbene and cis-stiff stilbene. Both systems exhibit unidirectional photoisomerization for each enantiomer as a result of their electronic prochirality. We simulate an experiment to demonstrate this effect in cis-stilbene based on its interaction with circularly polarized light. Our results highlight the drastic change in chiral behavior upon electronic excitation, opening up the possibility for asymmetric photochemistry from an effectively nonchiral starting point.

Synthesis of π-Extended Thiele’s and Chichibabin’s Hydrocarbons and Effect of the π-Congestion on Conformations and Electronic States

The biradicaloid of Chichibabin’s hydrocarbon exits in a unique thermal equilibrium between closed-shell singlet and open-shell triplet forms. Conceptually, the incorporation of nonplanar aromatic groups, such as anthraquinodimethane (AQD), in these species could bring about stabilization of the individual singlet and triplet spin biradicaloids by creating a high energy barrier for conformational interconversion between folded (singlet) and twisted (triplet) forms. Moreover, this alteration could introduce the possibility of controlling spin states through conformational changes induced by chemical and physical processes. Herein, we report the preparation of AQD-containing, π-extended Thiele’s (A-TH) and Chichibabin’s (A-CH) hydrocarbons, which have highly π-congested structures resulting from the presence of bulky 9-anthryl units. The π-congestion in these substances leads to steric frustration about carbon–carbon double bonds and creates flexible dynamic motion with a moderate activation barrier between folded singlet and twisted triplet states. These constraints make it possible to isolate the twisted triplet state of A-CH. In addition, simple mechanical grinding of the folded singlet of A-CH produces the twisted triplet.