Photoinduced Selective B-H Activation of nido-Carboranes.

The development of new synthetic methods for B-H bond activation has been an important research area in boron cluster chemistry, which may provide opportunities to broaden the application scope of boron clusters. Herein, we present a new reaction strategy for the direct site-selective B-H functionalization of nido-carboranes initiated by photoinduced cage activation via a noncovalent cage···π interaction. As a result, the nido-carborane cage radical is generated through a single electron transfer from the 3D nido-carborane cage to a 2D photocatalyst upon irradiation with green light. The resulting transient nido-carborane cage radical could be directly probed by an advanced time-resolved EPR technique. In air, the subsequent transformations of the active nido-carborane cage radical have led to efficient and selective B-N, B-S, and B-Se couplings in the presence of N-heterocycles, imines, thioethers, thioamides, and selenium ethers. This protocol also facilitates both the late-stage modification of drugs and the synthesis of nido-carborane-based drug candidates for boron neutron capture therapy (BNCT).

A Voyage into Chemical Bonds and Aromaticity.

This Guest Editorial introduces the special collection entitled "Frontiers in Chemical Bonding and Aromaticity" as a tribute to Professor Miquel Solà on the occasion of his 60th birthday.

Multiple hydrogen-bonded dimers: are only the frontier atoms relevant?

Non-frontier atom exchanges in hydrogen-bonded aromatic dimers can induce significant interaction energy changes (up to 6.5 kcal mol-1). Our quantum-chemical analyses reveal that the relative hydrogen-bond strengths of N-edited guanine-cytosine base pair isosteres, which cannot be explained from the frontier atoms, follow from the charge accumulation in the monomers.

Facile Construction of New Hybrid Conjugation via Boron Cage Extension.

Aromatic polycyclic systems have been extensively utilized as structural subunits for the preparation of various functional molecules. Currently, aromatics-based polycyclic systems are predominantly generated from the extension of two-dimensional (2D) aromatic rings. In contrast, polycyclic compounds based on the extension of three-dimensional (3D) aromatics such as boron clusters are less studied. Here, we report three types of boron cluster-cored tricyclic molecular systems, which are constructed from a 2D aromatic ring, a 3D aromatic nido-carborane, and an alkyne. These new tricyclic compounds can be facilely accessed by Pd-catalyzed B-H activation and the subsequent cascade heteroannulation of carborane and pyridine with an alkyne in an isolated yield of up to 85% under mild conditions without any additives. Computational results indicate that the newly generated ring from the fusion of the 3D carborane, the 2D pyridyl ring, and an alkyne is non-aromatic. However, such fusion not only leads to a 1H chemical shift considerably downfield shifted owing to the strong diatropic ring current of the embedded carborane but also devotes to new/improved physicochemical properties including increased thermal stability, the emergence of a new absorption band, and a largely red-shifted emission band and enhanced emission efficiency. Besides, a number of bright, color-tunable solid emitters spanning over all visible light are obtained with absolute luminescence efficiency of up to 61%, in contrast to aggregation-caused emission quenching of, e.g., Rhodamine B containing a 2D-aromatics-fused structure. This work demonstrates that the new hybrid conjugated tricyclic systems might be promising structural scaffolds for the construction of functional molecules.

Single─Not Double─3D-Aromaticity in an Oxidized Closo Icosahedral Dodecaiodo-Dodecaborate Cluster.

3D-aromatic molecules with (distorted) tetrahedral, octahedral, or spherical structures are much less common than typical 2D-aromatic species or even 2D-aromatic-in-3D systems. Closo boranes, [BnHn]2- (5 ≤ n ≤ 14) and carboranes are examples of compounds that are singly 3D-aromatic, and we now explore if there are species that are doubly 3D-aromatic. The most widely known example of a species with double 2D-aromaticity is the hexaiodobenzene dication, [C6I6]2+. This species shows π-aromaticity in the benzene ring and σ-aromaticity in the outer ring formed by the iodine substituents. Inspired by the hexaiodobenzene dication example, in this work, we explore the potential for double 3D-aromaticity in [B12I12]0/2+. Our results based on magnetic and electronic descriptors of aromaticity together with 11B{1H} NMR experimental spectra of boron-iodinated o-carboranes suggest that these two oxidized forms of a closo icosahedral dodecaiodo-dodecaborate cluster, [B12I12] and [B12I12]2+, behave as doubly 3D-aromatic compounds. However, an evaluation of the energetic contribution of the potential double 3D-aromaticity through homodesmotic reactions shows that delocalization in the I12 shell, in contrast to the 10σ-electron I62+ ring in the hexaiodobenzene dication, does not contribute to any stabilization of the system. Therefore, the [B12I12]0/2+ species cannot be considered as doubly 3D-aromatic.

Rational design of iron catalysts for C-X bond activation.

We have quantum chemically studied the iron-mediated CX bond activation (X = H, Cl, CH3 ) by d8 -FeL4 complexes using relativistic density functional theory at ZORA-OPBE/TZ2P. We find that by either modulating the electronic effects of a generic iron-catalyst by a set of ligands, that is, CO, BF, PH3 , BN(CH3 )2 , or by manipulating structural effects through the introduction of bidentate ligands, that is, PH2 (CH2 )n PH2 with n = 6-1, one can significantly decrease the reaction barrier for the CX bond activation. The combination of both tuning handles causes a decrease of the CH activation barrier from 10.4 to 4.6 kcal mol-1 . Our activation strain and Kohn-Sham molecular orbital analyses reveal that the electronic tuning works via optimizing the catalyst-substrate interaction by introducing a strong second backdonation interaction (i.e., "ligand-assisted" interaction), while the mechanism for structural tuning is mainly caused by the reduction of the required activation strain because of the pre-distortion of the catalyst. In all, we present design principles for iron-based catalysts that mimic the favorable behavior of their well-known palladium analogs in the bond-activation step of cross-coupling reactions.

Pioneering the Power of Twin Bonds in a Revolutionary Double Bond Formation. Unveiling the True Identity of o-Carboryne as o-Carborene.

The homolytic elimination of two H atoms from two adjacent carbons in benzene results in the aromatic product o-benzyne. In a similar way, the homolytic elimination of two H atoms from the two adjacent carbons in 1,2-C2 B10 H12 results in the aromatic product o-carboryne. In this work, we provide experimental and computational evidences that despite the similarity of o-carboryne and o-benzyne, the nature of the C-C bond generated between two adjacent carbons that lose H atoms is different. While in o-benzyne the C-C bond behaves as a triple bond, in o-carboryne the C-C bond is a double bond. Therefore, we must stop naming 1,2-dehydro-o-carboryne as o-carboryne but instead call it o-carborene.

Controlling the Diradical Character of Thiele Like Compounds.

Organic diradicals play an important role in many fields of chemistry, biochemistry, and materials science. In this work, by means of high-level theoretical calculations, we have investigated the effect of representative chemical substituents in p-quinodimethane (pQDM) and Thiele's hydrocarbons with respect to the singlet-triplet energy gap, a feature characterizing their diradical character. We show how the nature of the substituents has a very important effect in controlling the singlet-triplet energy gap so that several compounds show diradical features in their ground electronic state. Importantly, steric effects appear to play the most determinant role for pQDM analogues, with minor effects of the substituents in the central ring. For Thiele like compounds, we found that electron-withdrawing groups in the central ring favor the quinoidal form with a low or almost null diradical character, whereas electron-donating group substituents favor the aromatic-diradical form if the electron donation does not exceed 6-π electrons. In this case, if there is an excess of electron donation, the diradical character is reduced. The electronic spectrum of these compounds is also calculated, and we predict that the most intense bands occur in the visible region, although in some cases characteristic electronic transition in the near-IR region may appear.

Strengthened cooperativity of DNA-based cyclic hydrogen-bonded rosettes by subtle functionalization.

Cooperative effects cause extra stabilization of hydrogen-bonded supramolecular systems. In this work we have designed hydrogen-bonded rosettes derived from a guanine-cytosine Janus-type motif with the aim of finding a monomer that enhances the synergy of supramolecular systems. For this, relativistic dispersion-corrected density functional theory computations have been performed. Our proposal involves a monomer with three hydrogen-bonds pointing in the same direction, which translates into shorter bonds, stronger donor-acceptor interactions, and more attractive electrostatic interactions, thus giving rise to rosettes with strengthened cooperativity. This newly designed rosette has triple the cooperativity found for the naturally occurring guanine quadruplex.

Unravelling Enzymatic Features in a Supramolecular Iridium Catalyst by Computational Calculations.

Non-biological catalysts following the governing principles of enzymes are attractive systems to disclose unprecedented reactivities. Most of those existing catalysts feature an adaptable molecular recognition site for substrate binding that are prone to undergo conformational selection pathways. Herein, we present a non-biological catalyst that is able to bind substrates via the induced fit model according to in-depth computational calculations. The system, which is constituted by an inflexible substrate-recognition site derived from a zinc-porphyrin in the second coordination sphere, features destabilization of ground states as well as stabilization of transition states for the relevant iridium-catalyzed C-H bond borylation of pyridine. In addition, this catalyst appears to be most suited to tightly bind the transition state rather than the substrate. Besides these features, which are reminiscent of the action modes of enzymes, new elementary catalytic steps (i. e. C-B bond formation and catalyst regeneration) have been disclosed owing to the unique distortions encountered in the different intermediates and transition states.

Probing the Lewis Acidity of Boronic Acids through Interactions with Arene Substituents.

Boronic acids are Lewis acids that exist in equilibrium with boronate forms in aqueous solution. Here we experimentally and computationally investigated the Lewis acidity of 2,6-diarylphenylboronic acids; specially designed phenylboronic acids that possess two flanking aromatic rings with tunable aromatic character. Hammett analysis of 2,6-diarylphenylboronic acids reveals that their Lewis acidity remains unchanged upon the introduction of EWG/EDG at the distant para position of the flanking aromatic rings. Structural and computational studies demonstrate that polar-π interactions and solvation effects contribute to the stabilization of boronic acids and boronate forms by aromatic rings. Our physical-organic chemistry work highlights that boronic acids and boronates can be stabilized by aromatic systems, leading to an important molecular knowledge for rational design and development of boronic acid-based catalysts and inhibitors of biomedically important proteins.

C(spn )-X (n=1-3) Bond Activation by Palladium.

We have studied the palladium-mediated activation of C(spn )-X bonds (n = 1-3 and X = H, CH3 , Cl) in archetypal model substrates H3 C-CH2 -X, H2 C=CH-X and HC≡C-X by catalysts PdLn with Ln = no ligand, Cl- , and (PH3 )2 , using relativistic density functional theory at ZORA-BLYP/TZ2P. The oxidative addition barrier decreases along this series, even though the strength of the bonds increases going from C(sp3 )-X, to C(sp2 )-X, to C(sp)-X. Activation strain and matching energy decomposition analyses reveal that the decreased oxidative addition barrier going from sp3 , to sp2 , to sp, originates from a reduction in the destabilizing steric (Pauli) repulsion between catalyst and substrate. This is the direct consequence of the decreasing coordination number of the carbon atom in C(spn )-X, which goes from four, to three, to two along this series. The associated net stabilization of the catalyst-substrate interaction dominates the trend in strain energy which indeed becomes more destabilizing along this same series as the bond becomes stronger from C(sp3 )-X to C(sp)-X.

C-X Bond Activation by Palladium: Steric Shielding versus Steric Attraction.

The C-X bond activation (X = H, C) of a series of substituted C(n°)-H and C(n°)-C(m°) bonds with C(n°) and C(m°) = H3 C- (methyl, 0°), CH3 H2 C- (primary, 1°), (CH3 )2 HC- (secondary, 2°), (CH3 )3 C- (tertiary, 3°) by palladium were investigated using relativistic dispersion-corrected density functional theory at ZORA-BLYP-D3(BJ)/TZ2P. The effect of the stepwise introduction of substituents was pinpointed at the C-X bond on the bond activation process. The C(n°)-X bonds become substantially weaker going from C(0°)-X, to C(1°)-X, to C(2°)-X, to C(3°)-X because of the increasing steric repulsion between the C(n°)- and X-group. Interestingly, this often does not lead to a lower barrier for the C(n°)-X bond activation. The C-H activation barrier, for example, decreases from C(0°)-X, to C(1°)-X, to C(2°)-X and then increases again for the very crowded C(3°)-X bond. For the more congested C-C bond, in contrast, the activation barrier always increases as the degree of substitution is increased. Our activation strain and matching energy decomposition analyses reveal that these differences in C-H and C-C bond activation can be traced back to the opposing interplay between steric repulsion across the C-X bond versus that between the catalyst and substrate.

Through-Space Stabilization of an Imidazolium Cation by Aromatic Rings.

Imidazole-based compounds are widely found in natural products, synthetic molecules, and biomolecules. Noncovalent interactions between the imidazole ring and other functional groups play an important role in determining the function of diverse molecules. However, there is a limited understanding of the underlying noncovalent interactions between imidazoles and aromatic systems. In this work, we report physical-organic chemistry studies on 2-(2,6-diarylphenyl)-1H-imidazoles and their protonated forms to investigate the noncovalent interactions between the central imidazole ring and two flanking aromatic rings possessing substituents at the para/meta position. Hammett analysis revealed that pKa values and proton affinities correlate well with Hammett σ values of para-substituents at the flanking rings. Additional quantitative Kohn-Sham molecular orbital and energy decomposition analyses reveal that through-space π-π interactions and NH-π interactions contribute to the intramolecular stabilization of the imidazolium cation. The results are important because they clearly demonstrate that the imidazolium cation forms energetically favorable noncovalent interactions with aromatic rings via the through-space effect, a knowledge that can be used in rational drug and catalyst design.

Probing Noncovalent Interactions in [3,3]Metaparacyclophanes.

Arene-arene interactions are fundamentally important in molecular recognition. To precisely probe arene-arene interactions in cyclophanes, we designed and synthesized (2,6-phenol)paracyclophanes and (2,6-aniline)paracyclophanes that possess two aromatic rings in close proximity. Fine-tuning the aromatic character of one aromatic ring by fluorine substituents enables investigations on the intramolecular interactions between the electron-rich phenol and aniline with tetra-H- and tetra-F-substituted benzene. pKa measurements revealed that the tetra-F-template increases the acidity of the phenol (ΔpKa = 0.55). X-ray crystallography and computational analyses demonstrated that all [3,3]metaparacyclophanes adopt cofacial parallel conformations, implying the presence of π-π stacking interactions. Advanced quantum chemical analyses furthermore revealed that both electrostatic interactions and orbital interactions provide the key contribution to the structure and stability of [3,3]metaparacyclophanes.

Path-dependency of energy decomposition analysis & the elusive nature of bonding.

Here, we provide evidence of the path-dependency of the energy components of the energy decomposition analysis scheme, EDA, by studying a set of thirty-one closed-shell model systems with the D2h symmetry point group. For each system, we computed EDA components from nine different pathways and numerically showed that the relative magnitudes of the components differ substantially from one path to the other. Not surprisingly, yet unfortunately, the most significant variations in the relative magnitudes of the EDA components appear in the case of species with bonds within the grey zone of covalency and ionicity. We further discussed that the role of anions and their effect on arbitrary Pauli repulsion energy components affects the nature of bonding defined by EDA. The outcome variation by the selected partitioning scheme of EDA might bring arbitrariness when a careful comparison is overlooked.

Aromaticity and Extrusion of Benzenoids Linked to [o-COSAN]- : Clar Has the Answer.

Benzene and pyrene can be synthetically linked to [o-COSAN]- keeping their aromaticity. In contrast, naphthalene and anthracene are extruded in the same reaction. We have proven that extrusion is only favorable if the number of Clar's π-sextets remains constant. Thus, Clar has the answer to whether an attached polycyclic aromatic hydrocarbon to [o-COSAN]- is extruded or not.

Methyl Substitution Destabilizes Alkyl Radicals.

We have quantum chemically investigated how methyl substituents affect the stability of alkyl radicals Mem H3-m C⋅ and the corresponding Mem H3-m C-X bonds (X = H, CH3 , OH; m = 0 - 3) using density functional theory at M06-2X/TZ2P. The state-of-the-art in physical organic chemistry is that alkyl radicals are stabilized upon an increase in their degree of substitution from methyl

Do Sulfonamides Interact with Aromatic Rings?

Aromatic rings form energetically favorable interactions with many polar groups in chemical and biological systems. Recent molecular studies have shown that sulfonamides can chelate metal ions and form hydrogen bonds, however, it is presently not established whether the polar sulfonamide functionality also interacts with aromatic rings. Here, synthetic, spectroscopic, structural, and quantum chemical analyses on 2,6-diarylbenzenesulfonamides are reported, in which two flanking aromatic rings are positioned close to the central sulfonamide moiety. Fine-tuning the aromatic character by substituents on the flanking rings leads to linear trends in acidity and proton affinity of sulfonamides. This physical-organic chemistry study demonstrates that aromatic rings have a capacity to stabilize sulfonamides via through-space NH-π interactions. These results have implications in rational drug design targeting electron-rich aromatic rings in proteins.

The Chemical Bond: When Atom Size Instead of Electronegativity Difference Determines Trend in Bond Strength.

We have quantum chemically analyzed element-element bonds of archetypal Hn X-YHn molecules (X, Y=C, N, O, F, Si, P, S, Cl, Br, I), using density functional theory. One purpose is to obtain a set of consistent homolytic bond dissociation energies (BDE) for establishing accurate trends across the periodic table. The main objective is to elucidate the underlying physical factors behind these chemical bonding trends. On one hand, we confirm that, along a period (e. g., from C-C to C-F), bonds strengthen because the electronegativity difference across the bond increases. But, down a period, our findings constitute a paradigm shift. From C-F to C-I, for example, bonds do become weaker, however, not because of the decreasing electronegativity difference. Instead, we show that the effective atom size (via steric Pauli repulsion) is the causal factor behind bond weakening in this series, and behind the weakening in orbital interactions at the equilibrium distance. We discuss the actual bonding mechanism and the importance of analyzing this mechanism as a function of the bond distance.