Valence Isomerization Research Articles

Boron-Nitrogen-Containing Benzene Valence Isomers.

Benzene is one of the most ubiquitous structural motifs in chemistry. The valence isomers of benzene have also attracted synthetic chemists' attention due to their unique structures, bonding, and reactivity. We have been investigating boron-nitrogen-containing benzene valence isomers via photoisomerization of 1,2-azaborines. In this contribution, we summarize recent developments of these highly strained BN-heterocyclic compounds including their synthesis, characterization, proposed mechanism of formation, and their potential applications.

Benzvalene-like Carboranes: Genuine Rule Breakers and Good Kinetic Stability.

Substituents are widespread in chemistry, but it has remained quite difficult to reliably determine the thermodynamic and kinetic stabilities of substituted compounds, though they are key to helping establish a structural rule and synthetic viability, respectively. As an important class of valence isomers in the benzene family, benzvalene-like structures have been extensively studied in systems associated with electron-neutral (i.e., C, Si, Ge, Pb, and Sn) and electron-rich (e.g., P) skeletons. However, stable benzvalene-like examples associated with electron-deficient skeletons have been very limited, possibly due to the very complicated bonding patterns of electron-deficient elements. Here, we performed an extensive structural search at the density functional theory (DFT) and CBS-QB3 level for the well-known six-vertex dicarboranes (C2B4R6), one of the central families of boranes and carboranes chemistry. We unexpectedly found that all of the previously reported benzvalene-like structures III (C2B4R6) as the long-chased "rule breaker" examples of the Wade-Mingos rule (W-M rule) are not the lowest-lying structures. Promisingly, for the first time, we succeeded in identifying several substituted III as the genuine lowest-lying structures and thus true "rule breakers." Thus, "benzvalenes" present hitherto the fourth member of the lowest-lying structural patterns for the family of six-vertex dicarboranes. Moreover, the presently revealed good kinetic stability of III' (C2B4R2R'4) over a wide range of substituents promoted us to recommend a novel kind of synthesizable carboranes beyond the Wade-Mingos rule, i.e., "benzvalene-like carboranes" with all of the classical skeletal atoms.

C3 Selective Hydroxylation of Pyridines via Photochemical Valence Isomerization of Pyridine N-Oxides.

The C-H hydroxylation of the pyridine C3 position is a highly desirable transformation but remains a great challenge due to the inherent electronic properties of this heterocycle core which bring difficulties in chemical reactivity and regioselectivity. Herein we present an efficient method for formal C3 selective hydroxylation of pyridines via photochemical valence isomerization of pyridine N-oxides. This metal-free transformation features operational simplicity and compatibility with a diverse array of functional groups, and the resulting hydroxylated products are amenable to further elaboration to synthetically useful building blocks. The synthetic utility of this strategy is further demonstrated in the effective late-stage functionalization of pyridine-containing medicinally relevant molecules and versatile derivatizations of 3-pyridinols.

Data Processing for Predicting DNA Damaging Properties of Complex UV Sources.

A growing number of experimental evidence emphasizes that photobiological phenomena are not always the sum of the effect of individual wavelengths present in the emission spectrum of light sources. Unfortunately, tools are missing to identify such non-additive effects and predict effects of various exposure conditions. In the present work, we addressed these points for the formation of pyrimidine dimers in DNA upon co-exposure to UVC, UVB and UVA radiation. We first applied a combination index approach to determine whether mixtures of theses UV ranges exhibited additive, inhibitory or synergistic effects on the formation of cyclobutane pyrimidine dimers, (6-4) photoproducts and Dewar valence isomers. A predictive approach based on an experimental design strategy was then used to quantify the contribution of each wavelength range to the formation of DNA photoproducts. The obtained models allowed us to accurately predict the level of pyrimidine dimers in DNA irradiated under different conditions. The data were found to be more accurate than those obtained with the simple additive approach underlying the use of action spectra. Experimental design thus appears as an attractive concept that could be widely applied in photobiology even for cellular experiments.

The Norbornadiene/Quadricyclane Pair as Molecular Solar Thermal Energy Storage System: Surface Science Investigations.

For the transition to renewable energy sources, novel energy storage materials are more important than ever. This review addresses so-called molecular solar thermal (MOST) systems, which appear very promising since they combine light harvesting and energy storing in one-photon one-molecule processes. The focus is on norbornadiene (NBD), a particularly interesting candidate, which is converted to the strained valence isomer quadricyclane (QC) upon irradiation. The stored energy can be released on demand. The energy-releasing cycloreversion from QC to NBD can be initiated by a thermal, catalytic, or electrochemical trigger. The reversibility of the energy storage and release cycles determines the general practicality of a MOST system. In the search for derivatives, which enable large-scale applications, fundamental surface science studies help to assess the feasibility of potential substituted NBD/QC couples. We include investigations under well-defined ultra-high vacuum (UHV) conditions as well as experiments in liquid phase. Next to the influence of the catalytically active surfaces on the isomerization between the two valence isomers, information on adsorption geometries, thermal stability limits, and reaction pathways of the respective molecules are discussed. Moreover, laboratory-scaled test devices demonstrate the proof of concept in various areas of application.

Reversible Restrain and Release of the Dynamic Valence Isomerization in a Shape-shifting Bullvalene by Complex Formation.

In search for structural features that enable the control of the valence isomerization of the fluxional bullvalene, a bullvalene-bis(harmane) conjugate is identified that acts as chelating ligand in complexes with metal ions. Spectrometric titrations show that this ligand forms 1 : 1 complexes with Ag+, Cu+, Cu2+, and Zn2+. Most importantly, detailed NMR-spectroscopic analysis at different temperatures reveals that the complexation with Ag+ strongly affects the dynamic isomerization of the bullvalene unit of the ligand such that only one predominant valence isomer is formed, even at 5 °C. Detailed 1H-NMR-spectroscopic studies disclose an increased barrier (~11 kJ mol-1) of the Cope rearrangement. Furthermore, the addition of hexacyclene displaces the Ag+ from the complex, so that the valence isomerization is accelerated and an equilibrium with two predominant isomers is formed. In turn, repeated addition of Ag+ regains the complex with the restrained isomerization of the bullvalene unit. This method to control the valence isomerism by straightforward chemical stimuli may be used to simplify structural analysis at elevated temperatures, i. e. a feature not available so far with bullvalenes, and it may be employed as functional element in dynamic supramolecular assemblies.

Vibrational analysis, frontier orbitals, optical and structural properties of 1, 2-dithiete and di-thiolene derivatives: A quantum mechanical study

The organic chemistry of sulfur-containing compounds has attracted much research due to its importance in biology, biochemistry, and various industries. 1, 2-Dithiete is a cyclic and unsaturated organo-sulfuric compound. This compound can be converted to di-thiolene (its valence isomer). The structure, electronic properties, and energy of two valence isomers, i.e. di-thiolene and 1,2-dithiete (III) were studied using density functional theory (DFT). Results showed that di-thiolene has two conformers (s-trans (I), s-cis (II)) and the s-trans is more stable. The electron donor and acceptor substituents on the carbon atoms increase the polarity difference between these two valence isomers. The dipole moment and polarizability of di-thiolenes were also greater than those of 1, 2-dithietes. Conversion of 1,2-dithiete to di-thiolene, structural properties, polarity, and polarizability of some derivatives of these two valence isomers were examined by quantum mechanical method at the level of B3LYP theory and 6-311++g (d, p) bases sets using Gaussian09 computational program. This conversion occurs through the s-cis conformation pathway and is an exothermic reaction. In the cases of ten derivatives of C2S2R2 (R = CH3, CF3, CN, OCH3, CH2CH3, t-Bu, Ph, Cyclopropyl, Cyclobutyl, and Cyclopentyl) the s-cis conformers are so unstable that they are not obtained as local structures. In general, s-trans di-thiolenes are more stable than their cyclic valence isomers (1,2-dithietes). Of course, the degree of stability depends on substituent identity.

Metal-catalyzed valence isomerization of a methylene(thioxo)phosphorane to a thiaphosphirane.

We explored coordination chemistry associated with valence isomerization between a methylene(thioxo)phosphorane (MTP) and a thiaphosphirane. For this purpose, we developed the selective synthesis of a MTP by eliminating chlorodimethylphenylsilane from the corresponding chlorophosphine sulfide. Treatment of the MTP with an equivalent amount of pentafluorophenylgold(I) complex resulted in the formation of a thiaphosphirane gold(I) complex, which likely proceeds via an η2-P,C-MTP gold complex. The MTP undergoes a valence isomerization catalyzed by copper(I) chloride to furnish a transition metal-free thiaphosphirane. Computational studies proposed a plausible mechanism involving a Cu-assisted cyclization reaction.

A guide to bullvalene stereodynamics.

Here, we analyze the stereodynamic properties of bullvalenes using principal moments of inertia and exit vector plots to draw comparisons with commonly used ring systems in medicinal chemistry. To aid analyses, we first classify (i) the four elementary rearrangement steps available to substituted bullvalenes, which (ii) can be described by applying positional descriptors (α, β, γ, and δ) to the substituents. We also (iii) derive an intuitive equation to calculate the number of isomers for a given bullvalene system. Using DFT-modelled structures for di-, tri-, and tetrasubstituted bullvalenes, generated using a newly developed computational tool (bullviso), we show that their 3D shapes and the exit vectors available from the bullvalene scaffold make them comparable to other bioisosteres currently used to replace planar aromatic ring systems in drug discovery. Unlike conventional ring systems, the shapeshifting valence isomerism of bullvalenes gives rise to numerous shapes and substituent relationships attainable as a concentration-independent dynamic covalent library from a single compound. We visualize this property by applying population weightings to the principal moments of inertia and exit vector analyses to reflect the relative thermodynamic stabilities of the available isomers.

A Shapeshifting Roadmap for Polycyclic Skeletal Evolution.

Polycyclic ring systems are ubiquitous three-dimensional (3D) structural motifs central to the function of many biologically active small molecules and organic materials. Indeed, subtle changes to the overall molecular shape and connectivity of atoms in a polycyclic framework (i.e., isomerism) can drastically alter its function and properties. Unfortunately, direct evaluation of these structure-function relationships typically requires the development of distinct synthetic strategies toward a specific isomer. Dynamic, "shapeshifting" carbon cages present a promising approach for sampling isomeric chemical space but are often difficult to control and are largely limited to thermodynamic mixtures of positional isomers about a single core scaffold. Here, we describe the development of a new shapeshifting C9-chemotype and a chemical blueprint for its evolution into structurally and energetically diverse isomeric ring systems. By leveraging the unique molecular topology of π-orbitals interacting through-space (homoconjugation), a common skeletal ancestor evolved into a complex network of valence isomers. This unusual system represents an exceedingly rare small molecule capable of undergoing controllable and continuous isomerization processes through the iterative use of just two chemical steps (light and organic base). Computational and photophysical studies of the isomer network provide fundamental insight into the reactivity, mechanism, and role of homoconjugative interactions. Importantly, these insights may inform the rational design and synthesis of new dynamic, shapeshifting systems. We anticipate this process could be a powerful tool for the synthesis of structurally diverse, isomeric polycycles central to many bioactive small molecules and functional organic materials.

Exploiting Molecular Symmetry to Quantitatively Map the Excited-State Landscape of Iron-Sulfur Clusters.

Cuboidal [Fe4S4] clusters are ubiquitous cofactors in biological redox chemistry. In the [Fe4S4]1+ state, pairwise spin coupling gives rise to six arrangements of the Fe valences ("valence isomers") among the four Fe centers. Because of the magnetic complexity of these systems, it has been challenging to understand how a protein's active site dictates both the arrangement of the valences in the ground state as well as the population of excited-state valence isomers. Here, we show that the ground-state valence isomer landscape can be simplified from a six-level system in an asymmetric protein environment to a two-level system by studying the problem in synthetic [Fe4S4]1+ clusters with solution C3v symmetry. This simplification allows for the energy differences between valence isomers to be quantified (in some cases with a resolution of <0.1 kcal/mol) by simultaneously fitting the VT NMR and solution magnetic moment data. Using this fitting protocol, we map the excited-state landscape for a range of clusters of the form [(SIMes)3Fe4S4-X/L]n, (SIMes = 1,3-dimesityl-imidazol-4,5-dihydro-2-ylidene; n = 0 for anionic, X-type ligands and n = +1 for neutral, L-type ligands) and find that a single ligand substitution can alter the relative ground-state energies of valence isomers by at least 103 cm-1. On this basis, we suggest that one result of "non-canonical" amino acid ligation in Fe-S proteins is the redistribution of the valence electrons in the manifold of thermally populated excited states.

Stochastic Bullvalene Architecture Modulates Structural Rigidity in π-Rich Macromolecules.

The synthesis and processing of π-rich polymers found in novel electronics and textiles is difficult because chain stiffness leads to low solubility and high thermal transitions. The incorporation of "shape-shifting" molecular cages into π-rich backbone provides an ensemble of structural kinks to modulate chain architecture via a self-contained library of valence isomers. In this work, we report the synthesis and characterization of (bullvalene-co-phenylene)s that feature smaller persistence lengths than a prototypical rigid rod polymer, poly(p-phenylene). By varying the amount of bullvalene incorporation within a poly(p-phenylene) chain (0-50 %), we can tune thermal properties and solution-state conformation. These features are caused by stochastic bullvalene isomers within the polymer backbone that result in kinked architectures. Synthetically, bullvalene incorporation offers a facile method to decrease structural rigidity within π-rich materials without concomitant crystallization. VT NMR experiments confirm that these materials remain dynamic in solution, offering the opportunity for future stimuli-responsive applications.

Stochastic Bullvalene Architecture Modulates Structural Rigidity in π‐Rich Macromolecules

AbstractThe synthesis and processing of π‐rich polymers found in novel electronics and textiles is difficult because chain stiffness leads to low solubility and high thermal transitions. The incorporation of “shape‐shifting” molecular cages into π‐rich backbone provides an ensemble of structural kinks to modulate chain architecture via a self‐contained library of valence isomers. In this work, we report the synthesis and characterization of (bullvalene‐co‐phenylene)s that feature smaller persistence lengths than a prototypical rigid rod polymer, poly(p‐phenylene). By varying the amount of bullvalene incorporation within a poly(p‐phenylene) chain (0–50 %), we can tune thermal properties and solution‐state conformation. These features are caused by stochastic bullvalene isomers within the polymer backbone that result in kinked architectures. Synthetically, bullvalene incorporation offers a facile method to decrease structural rigidity within π‐rich materials without concomitant crystallization. VT NMR experiments confirm that these materials remain dynamic in solution, offering the opportunity for future stimuli‐responsive applications.

Norbornadiene/Quadricyclane System in the Spotlight: The Role of Rydberg States and Dynamic Electronic Correlation in a Solar‐Thermal Building Block

AbstractIn this contribution, we studied the photophysics and photochemistry of an archetypal molecular switch in terms of solar energy storage and release. In detail, we characterized the valence and Rydberg states of norbornadiene (NBD) and quadricyclane (QC) by means of CASPT2//CASSCF theory level, finding a good agreement of the calculated vertical excitation energies with the experimental counterparts. The NBD↔QC thermal and photochemical valence isomerization [2π+2π] reactions have been addressed and investigated. Low energy crossing points between excited states were identified for both the NBD↔QC photochemical reactions, through the calculation of minimum energy paths which revealed that the photochemistry is ruled by the deformation of two coupled reaction coordinates. Such coordinates were also used to build potential energy surfaces through relaxed energy scans with the goal of building a simplified, still accurate, model system able to catch the NBD↔QC photorelaxation. Also, the S1/S0 respective conical intersection were characterized and related to the reaction quantum yield. Interestingly, we found that reverse photoisomerization from QC to the NBD progenitor could in principle occur by direct excitation of σ‐3s and σ‐3p Rydberg excited states in the UV spectral range. In both NBD and QC photoreactivity, the doubly excited valence state has shown to play a crucial role for reaching crossing points leading to nonadiabatic population transfers.

Silyl Groups Are Strong Dispersion Energy Donors.

We present an experimental and computational study to investigate noncovalent interactions between silyl groups that are often employed as "innocent" protecting groups. We chose an extended cyclooctatetraene (COT)-based molecular balance comprising unfolded (1,4-disubstituted) and folded (1,6-disubstituted) valance bond isomers that typically display remote and close silyl group contacts, respectively. The thermodynamic equilibria were determined using nuclear magnetic resonance measurements. Additionally, we utilized Boltzmann weighted symmetry-adapted perturbation theory (SAPT) at the sSAPT0/aug-cc-pVDZ level of theory to dissect and quantify noncovalent interactions. Apart from the extremely bulky tris(trimethylsilyl)silyl "supersilyl" group, there is a preference for the folded 1,6-COT valence isomer, with London dispersion interactions being the main stabilizing factor. This makes silyl groups excellent dispersion energy donors, a finding that needs to be taken into account in synthesis planning.

An Iron‐Catalyzed Route to Dewar 1,3,5‐Triphosphabenzene and Subsequent Reactivity

AbstractThe application of an alkyne cyclotrimerization regime with an [Fe(salen)]2‐μ‐oxo (1) catalyst to triphenylmethylphosphaalkyne (2) yields gram‐scale quantities of 2,4,6‐tris(triphenylmethyl)‐Dewar‐1,3,5‐triphosphabenzene (3). Bulky lithium salt LiHMDS facilitates a rearrangement of 3 to the 1,3,5‐triphosphabenzene valence isomer (3′), which subsequently undergoes an intriguing phosphorus migration reaction to form the ring‐contracted species (3′′). Density functional theory calculations provide a plausible mechanism for this rearrangement. Given the stability of 3, a diverse array of unprecedented transformations was investigated. We report novel crystallographically characterized products of successful nucleophilic/electrophilic addition and protonation/oxidation reactions.

An Iron-Catalyzed Route to Dewar 1,3,5-Triphosphabenzene and Subsequent Reactivity.

The application of an alkyne cyclotrimerization regime with an [Fe(salen)]2‐μ‐oxo (1) catalyst to triphenylmethylphosphaalkyne (2) yields gram‐scale quantities of 2,4,6‐tris(triphenylmethyl)‐Dewar‐1,3,5‐triphosphabenzene (3). Bulky lithium salt LiHMDS facilitates a rearrangement of 3 to the 1,3,5‐triphosphabenzene valence isomer (3′), which subsequently undergoes an intriguing phosphorus migration reaction to form the ring‐contracted species (3′′). Density functional theory calculations provide a plausible mechanism for this rearrangement. Given the stability of 3, a diverse array of unprecedented transformations was investigated. We report novel crystallographically characterized products of successful nucleophilic/electrophilic addition and protonation/oxidation reactions.

Surface Chemistry of the Molecular Solar Thermal Energy Storage System 2,3-Dicyano-Norbornadiene/Quadricyclane on Ni(111).

Molecular solar thermal (MOST) systems are a promising approach for the introduction of sustainable energy storage solutions. We investigated the feasibility of the dicyano‐substituted norbornadiene/quadricyclane molecule pair on Ni(111) for catalytic model studies. This derivatization is known to lead to a desired bathochromic shift of the absorption maximum of the parent compound. In our experiments further favorable properties were found: At low temperatures, both molecules adsorb intact without any dissociation. In situ temperature‐programmed HR‐XPS experiments reveal the conversion of (CN)2‐quadricyclane to (CN)2‐norbornadiene under energy release between 175 and 260 K. The absence of other surface species due to side reactions indicates full isomerization. Further heating leads to the decomposition of the molecular framework into smaller carbonaceous fragments above 290 K and finally to amorphous structures, carbide and nitride above 400 K. DFT calculations gave insights into the adsorption geometries. (CN)2‐norbornadiene is expected to interact stronger with the surface, with flat configurations being favorable. (CN)2‐quadricyclane exhibits smaller adsorption energies with negligible differences for flat and side‐on geometries. Simulated XP spectra are in good agreement with experimental findings further supporting the specific spectroscopic fingerprints for both valence isomers.

A theoretical study of the valence tautomerism of 1H-pyrazolium-4-olates (X = O) and related compounds (X = S, Se, NH): relative stabilities, protonation effects, and tautomerization barriers

The valence isomerism of a series of heterocyclic mesomeric betaines (HMBs) belonging to class 5, called pseudo-semi-conjugated HMBs, has been studied theoretically both the neutral and the protonated species. These HMBs are 1H-pyrazol-2-ium-4-olates and related compounds where the oxygen atom has been replaced by S, Se atoms, and an NH group. The main conclusion of the present work is that the ring/open valence tautomerism is possible both for neutral and protonated although it has never been observed experimentally.

Total Irregularity Strengths of a Disjoint Union of (4,6)-Fullerene Graphs

A fullerene is a polyhedral molecule made entirely of carbon atoms other than graphite and diamond. Mathematical chemistry or Chemical graph theory as a combination of chemistry and graph theory studies the physical properties of mathematically modeled chemical compounds. Graph labeling is a vital area of graph theory that has applications in both physical and social sciences. For example, in chemistry vertex labeling is used in the constitution of valence isomers and transition labeling to study chemical reaction networks. A (4,6)-fullerene graph is a mathematical model of a (4,6)-fullerene molecule. It is a cubic-regular planar graph whose faces are squares and hexagons. In this article, we study the total vertex irregularity strength and the total edge irregularity strength of a disjoint union of (4,6)-fullerene graphs and provide their exact values.