RESUMEN
Spectroscopic properties are commonly used in the experimental evaluation of ground- and excited-state aromaticity in expanded porphyrins. Herein, we investigate if the defining photophysical properties still hold for a diverse set of hexaphyrins with varying redox states, topologies, peripheral substitutions, and core-modifications. By combining TD-DFT calculations with several aromaticity descriptors and chemical compound space maps, the intricate interplay between structural planarity, aromaticity, and absorption spectra is elucidated. Our results emphasize that the general assumption that antiaromatic porphyrinoids exhibit significantly attenuated absorption bands as compared to aromatic counterparts does not hold even for the unsubstituted hexaphyrin macrocycles. To connect the spectroscopic properties to the hexaphyrins' aromaticity behaviour, we analyzed chemical compound space maps defined by the various aromaticity indices. The intensity of the Q-band is not well described by the macrocyclic aromaticity. Instead, the degeneracy of the frontier molecular orbitals, the HOMO-LUMO gap, and the |ΔHOMO-ΔLUMO|2 values appear to be better indicators to identify hexaphyrins with enhanced light-absorbing abilities in the near-infrared region. Regions with highly planar hexaphyrin structures, both aromatic and antiaromatic, are characterized by an intense B-band. Hence, we advise using a combination of global and local aromaticity descriptors rooted in different criteria to assess the aromaticity of expanded porphyrins instead of solely relying on the absorption spectra.
RESUMEN
Due to the enormous size of the chemical compound space, usually only small regions are traversed with traditional direct molecular design approaches making the discovery for novel functionalized molecules for nonlinear optical applications challenging. By applying inverse molecular design algorithms, we aim to efficiently explore larger regions of the compound space in search of promising hexaphyrin-based molecular switches as measured by their first-hyperpolarizability (ßHRS) contrast. We focus on the 28R â 30R switch with a functionalization pattern allowing for centrosymmetric OFF states yielding zero ßHRS response. This switch is particularly challenging as full meso-substitution with a single type of functional group or core-modifications result in almost no contrast enhancement. We carried out four inverse design procedures during which two sets of core-modifications and three sets of meso-substitutions sites were systematically optimized. All 4 optimal switches are characterized by a mix of meso-substitutions and core-modifications, of which the best performing switch yields a 10-fold improvement over the parent macrocycle. Throughout the inverse design procedures, we collected and analyzed a database biased towards high NLO contrasts that contains 277 different patterns for hexaphyrin-based switches. We derived three design rules to obtain highly functional 28R â 30R NLO switches: (I) a combination of 2 strong EWG and 1 EDG group is the ideal recipe for increasing the NLO contrast, though their position also plays an important role. (II) The type of core-modification is less important when only the diagonal positions are core-modified. Switches with 4 core-modifications show a clear preference for oxygen. (III) Keeping centrosymmetry in the OFF state remains highly beneficial given the investigated functionalization pattern. Finally, we have demonstrated that combining meso-substitutions with core-modifications can synergistically improve the NLO contrast.
RESUMEN
In the current literature, many non-covalent interaction (NCI) donors have been proposed that can potentially catalyze Diels-Alder (DA) reactions. In this study, a detailed analysis of the governing factors in Lewis acid and non-covalent catalysis of three types of DA reactions was carried out, for which we selected a set of hydrogen-, halogen-, chalcogen-, and pnictogen-bond donors. We found that the more stable the NCI donor-dienophile complex, the larger the reduction in DA activation energy. We also showed that for active catalysts, a significant part of the stabilization was caused by orbital interactions, though electrostatic interactions dominated. Traditionally, DA catalysis was attributed to improved orbital interactions between the diene and dienophile. Recently, Vermeeren and co-workers applied the activation strain model (ASM) of reactivity, combined with the Ziegler-Rauk-type energy decomposition analysis (EDA), to catalyzed DA reactions in which energy contributions for the uncatalyzed and catalyzed reaction were compared at a consistent geometry. They concluded that reduced Pauli repulsion energy, and not enhanced orbital interaction energy, was responsible for the catalysis. However, when the degree of asynchronicity of the reaction is altered to a large extent, as is the case for our studied hetero-DA reactions, the ASM should be employed with caution. We therefore proposed an alternative and complementary approach, in which EDA values for the catalyzed transition-state geometry, with the catalyst present or deleted, can be compared one to one, directly measuring the effect of the catalyst on the physical factors governing the DA catalysis. We discovered that enhanced orbital interactions are often the main driver for catalysis and that Pauli repulsion plays a varying role.
Asunto(s)
Ácidos de Lewis , Humanos , Ácidos de Lewis/química , Termodinámica , Catálisis , Reacción de CicloadiciónRESUMEN
Molecular switches, in which a stimulus induces a large and reversible change in molecular properties, are of significant interest in the domain of photonics. Due to their commutable redox states with distinct nonlinear optical (NLO) properties, hexaphyrins have emerged as a novel platform for multistate switches in nanoelectronics. In this study, we employ an inverse design algorithm to find functionalized 26Râ28R redox switches with maximal ßHRS contrast. We focus on the role of core modifications, since a synergistic effect with meso-substitutions was recently found for the 30R-based switch. In contrast to these findings, the inverse design optima and subsequent database analysis of 26R-based switches confirm that core modifications are generally not favored when high NLO contrasts are targeted. Moreover, while push-pull combinations enhance the NLO contrast for both redox switches, they prefer a different arrangement in terms of electron-donating and electron-withdrawing functional groups. Finally, we aim at designing a three-state 26Râ28Râ 30R switch with a similar NLO response for both ON states. Even though our best-performing three-state switch follows the design rules of the 30R-based component, our chemical compound space plots show that well-performing three-state switches can be found in regions shared by high-responsive 26R and 30R structures.
RESUMEN
The halogen bond complexes CF3Xâ¯Y and C2F3Xâ¯Y, with Y = furan, thiophene, selenophene and X = Cl, Br, I, have been studied by using DFT and CCSD(T) in order to understand which factors govern the interaction between the halogen atom X and the aromatic ring. We found that PBE0-dDsC/QZ4P gives an adequate description of the interaction energies in these complexes, compared to CCSD(T) and experimental results. The interaction between the halogen atom X and the π-bonds in perpendicular orientation is stronger than the interaction with the in-plane lone pairs of the heteroatom of the aromatic cycle. The strength of the interaction follows the trend Cl < Br < I; the chalcogenide in the aromatic ring nor the hybridization of the C−X bond play a decisive role. The energy decomposition analysis shows that the interaction energy is dominated by all three contributions, viz., the electrostatic, orbital, and dispersion interactions: not one factor dominates the interaction energy. The aromaticity of the ring is undisturbed upon halogen bond formation: the π-ring current remains equally strong and diatropic in the complex as it is for the free aromatic ring. However, the spin-orbit coupling between the singlet and triplet πâπ* states is increased upon halogen bond formation and a faster intersystem crossing between these states is therefore expected.
Asunto(s)
Halógenos , Halógenos/química , Electricidad EstáticaRESUMEN
Heteroaryl sulfonamides are important structural motifs in the medicinal and agrochemical industries. However, their synthesis often relies on the use of heteroaryl sulfonyl chlorides, which are unstable and toxic reagents. Herein, we report a protocol that allows direct oxidative coupling of heteroaryl thiols and primary amines, readily available and inexpensive commodity chemicals. The transformation proceeds under mild reaction conditions and yields the desired N-alkylated sulfonamides in good yields. N-alkyl heteroaryl sulfonamides can be further transformed using a microwave-promoted Fukuyama-Mitsunobu reaction to N,N-dialkyl heteroaryl sulfonamides. The developed protocols thus enable the preparation of previously difficult to prepare sulfonamides (toxic reagents, harsh conditions, and low yields) under mild conditions.
Asunto(s)
Aminas , Sulfonamidas , Aminas/química , Indicadores y Reactivos , Microondas , Compuestos de Sulfhidrilo , Sulfonamidas/químicaRESUMEN
Diels-Alder (DA) cycloadditions in reversible polymer networks are important for designing sustainable materials with self-healing properties. In this study, the DA kinetics of hydroxyl-substituted bis- and tetrafunctional furans with bis- and tris-functional maleimides, both containing ether-functionalized spacers, is investigated by modelling two equilibria representing the endo and exo cycloadduct formation. Concretely, the potential catalysis of the DA reaction through hydrogen bonding between hydroxyl of the furans and carbonyl of the maleimides or ether of the spacers is experimentally and theoretically scrutinized. Initial reaction rates and forward DA rate constants are determined by microcalorimetry at 20 °C for a model series of reversible networks, extended with (i) a hydroxyl-free network and hydroxyl-free linear or branched systems, and (ii) polypropylene glycol additives, increasing the hydroxyl concentration. A computational density-functional theory study is carried out on the endo and exo cycloadditions of furan and maleimide derivatives, representative for the experimental ones, in the absence and presence of ethylene glycol as additive. Additionally, an ester-substituted furan was investigated as a hydroxyl-free system for comparison. Experiment and theory indicate that the catalytic effect of H-bonding is absent or very limited. While increased concentration of H-bonding could in theory catalyze the DA reaction, the experimental results rule out this supposition.
Asunto(s)
Modelos Teóricos , Polímeros , Hidrógeno , Enlace de Hidrógeno , Cinética , Polímeros/químicaRESUMEN
Linear triatomic molecules (CO2, N2O, and OCS) are scrutinized for their propensity to form perpendicular tetrel (CO2 and OCS) or pnictogen (N2O) bonds with Lewis bases (dimethyl ether and trimethyl amine) as compared with their tendency to form end-on chalcogen bonds. Comparison of the IR spectra of the complexes with the corresponding monomers in cryogenic solutions in liquid argon enables to determine the stoichiometry and the nature of the complexes. In the present cases, perpendicular tetrel and pnictogen 1:1 complexes are identified mainly on the basis of the lifting of the degenerate ν 2 bending mode with the appearance of both a blue and a red shift. Van 't Hoff plots of equilibrium constants as a function of temperature lead to complexation enthalpies that, when converted to complexation energies, form the first series of experimental complexation energies on sp1 tetrel bonds in the literature, directly comparable to quantum-chemically obtained values. Their order of magnitude corresponds with what can be expected on the basis of experimental work on halogen and chalcogen bonds and previous computational work on tetrel bonds. Both the order of magnitude and sequence are in fair agreement with both CCSD(T) and DFA calculations, certainly when taking into account the small differences in complexation energies of the different complexes (often not more than a few kJ mol-1) and the experimental error. It should, however, be noted that the OCS chalcogen complexes are not identified experimentally, most probably owing to entropic effects. For a given Lewis base, the stability sequence of the complexes is first successfully interpreted via a classical electrostatic quadrupole-dipole moment model, highlighting the importance of the magnitude and sign of the quadrupole moment of the Lewis acid. This approach is validated by a subsequent analysis of the molecular electrostatic potential, scrutinizing the σ and π holes, as well as the evolution in preference for chalcogen versus tetrel bonds when passing to "higher" chalcogens in agreement with the evolution of the quadrupole moment. The energy decomposition analysis gives further support to the importance/dominance of electrostatic effects, as it turns out to be the largest attractive term in all cases considered, followed by the orbital interaction and the dispersion term. The natural orbitals for chemical valence highlight the sequence of charge transfer in the orbital interaction term, which is dominated by an electron-donating effect of the N or O lone-pair(s) of the base to the central atom of the triatomics, with its value being lower than in the case of comparable halogen bonding situations. The effect is appreciably larger for TMA, in line with its much higher basicity than DME, explaining the comparable complexation energies for DME and TMA despite the much larger dipole moment for DME.
RESUMEN
Despite the large variety of modified nucleosides that have been reported, the preparation of constrained 4'-spirocyclic adenosine analogues has received very little attention. We discovered that the [2+2]-cycloaddition of dichloroketene on readily available 4'-exo-methylene furanose sugars efficiently results in the diastereoselective formation of novel 4'-spirocyclobutanones. The reaction mechanism was investigated via density functional theory (DFT) and found to proceed either via a non-synchronous or stepwise reaction sequence, controlled by the stereochemistry at the 3'-position of the sugar substrate. The obtained dichlorocyclobutanones were converted into nucleoside analogues, providing access to a novel class of chiral 4'-spirocyclobutyl adenosine mimetics in eight steps from commercially available sugars. Assessment of the biological activity of designed 4'-spirocyclic adenosine analogues identified potent inhibitors for protein methyltransferase target PRMT5.
Asunto(s)
Adenosina/química , Nucleósidos/análogos & derivados , Nucleósidos/síntesis química , Carbohidratos/química , Reacción de Cicloadición , Teoría Funcional de la Densidad , Dicloroetilenos/química , Glicosilación , Metales/química , Estructura Molecular , Oxidación-Reducción , Estereoisomerismo , TermodinámicaRESUMEN
This study addresses one of the most important drawbacks inherently related to molecular searches in chemical compound space by greedy algorithms such as Best First Search and Genetic Algorithm, i.e., the large computational cost required to optimize one or more quantum-chemical properties. Significant speed-ups are obtained by initial property screening via predictive techniques starting already from very small databases. It is shown that the attainable acceleration depends heavily on the molecular properties, the predictive model, the molecular descriptor, and the current size of the database. We discuss the implementation and performance of predictive techniques in molecular searches based on a fixed molecular framework with a selection of sites to be filled with groups from a chemical fragment library. It is shown that for some properties speed-ups of a factor of 5 to even 20 can be obtained, while inverse design procedures on more complex properties still reach speed-ups of a factor of 2 without losing performance.
Asunto(s)
Química Computacional/métodos , Bibliotecas de Moléculas Pequeñas/química , Algoritmos , Modelos Químicos , Teoría CuánticaRESUMEN
The chalcogen bond has been acknowledged as an influential noncovalent interaction (NCI) between an electron-deficient chalcogen (donor) and a Lewis base (acceptor). This work explores the main features of chalcogen bonding through a large-scale computational study on a series of donors and acceptors spanning a wide range in strength and character of this type of bond: (benzo)chalcogenadiazoles (with Ch = Te/Se/S) versus halides and neutral Lewis bases with O, N, and C as donor atoms. We start from Pearson's hard and soft acids and bases (HSAB) principle, where the hard nature of the chalcogen bond is quantified through the molecular electrostatic potential and the soft nature through the Fukui function. The σ-holes are more pronounced when going down in the periodic table and their directionality matches the structural orientation of donors and acceptors in the complexes. The Fukui functions point toward an nâσ*-type interaction. The initial conjectures are further scrutinized using quantum mechanical methods, mostly relating to the systems' electron density. A Ziegler-Rauk energy decomposition analysis shows that electrostatics plays a distinctly larger role for the soft halides than for the hard, uncharged acceptors, associated with the softness matching within the HSAB principle. The natural orbital for chemical valence analysis confirms the nâσ* electron donation mechanism. Finally, the electron density and local density energy at the bond critical point in the quantum theory of atoms in molecules study and the position of the spikes in the reduced density gradient versus density plot in the NCI theory situate the chalcogen bond in the same range as strong hydrogen bonds. © 2017 Wiley Periodicals, Inc.
RESUMEN
An efficient metal-free cascade reaction between 1-dibromovinyl-2-nitro-substituted arenes and secondary amines results in the formation of polycyclic pseudoindoxyls in a single step. The reaction mechanism leading to these fused ring systems was investigated, and is believed to involve the initial formation of nitroarylated ynamines/ynamides. These intermediates cycloisomerize towards N-alkenyl-tethered 2-aminoisatogens via a carbene intermediate as demonstrated by QTAIM (quantum theory of atoms in molecules) and ELF (electron localization function) analysis. A subsequent intramolecular dipolar cycloaddition afforded the title compounds.
RESUMEN
In the last decade, halogen bonds, noncovalent interactions formed between positive regions in the electrostatic potential on halogen atoms, often referred to as σ-holes, and electron-rich sites, have gained a lot of interest. Recently, this interest has been expanded towards interactions with Groupâ V and Groupâ VI elements, giving rise to pnicogen and chalcogen bonds. Although chalcogen bonds have already shown some promising results for applications in crystallography and catalysis, experimental results characterising these noncovalent interactions remain scarce. In this combined experimental and theoretical study, original data allowing the characterization of Sâ â â O chalcogen bonds is obtained by studying the 1:1 molecular complexes between 2,2,4,4-tetrafluoro-1,3-dithiethane (C2 F4 S2 ) and dimethyl ether (DME). Ab initio calculations of the C2 F4 S2 â DME dimer yield two stable chalcogen-bonded isomers, the difference being the presence or absence of secondary Fâ â â H interactions. Liquid-krypton solutions containing C2 F4 S2 and DME were studied using FTIR and Raman spectroscopy. Upon subtraction of rescaled monomer spectra, clear complex bands are observed. The observed complexation shifts agree favourably with the ab initio calculated shifts of the chalcogen-bonded complexes. The 1:1 stoichiometry of the complex is confirmed and a complexation enthalpy of -13.5(1)â kJ mol-1 is found, which is in good agreement with the calculated values. A Ziegler-Rauk energy decomposition analysis revealed that electrostatic interactions prominently dominate over orbital interactions. Nevertheless, significant charge transfer occurs from the oxygen in DME to one of the sulfur atoms in C2 F4 S2 and the carbon along the extension of the chalcogen bond.
RESUMEN
There is an increasing interest in applying quantum chemistry to rationally design novel compounds with some desired characteristics. Furthermore, many applications require more than one property to be optimal. In this Concept, several inverse design strategies, based on the discrete best first search scheme, are introduced that allow for the simultaneous optimization of multiple properties or the optimization of the most vital target property with constraints for secondary properties. A detailed assessment of the different optimization techniques is carried out, and special attention is paid to improve the cost efficacy and performance by tuning the process parameters. Our suggested protocol allows for a more successful optimization routine when additional boundary conditions are desired.
RESUMEN
The contributions of covalent and noncovalent interactions to the formation of classical adducts of bulky Lewis acids and bases and frustrated Lewis pairs (FLPs) were scrutinized by using various conceptual quantum chemical techniques. Significantly negative complexation energies were calculated for fourteen investigated Lewis pairs containing bases and acids with substituents of various sizes. A Ziegler-Rauk-type energy decomposition analysis confirmed that two types of Lewis pairs can be distinguished on the basis of the nature of the primary interactions between reactants; dative-bond formation and concomitant charge transfer from the Lewis base to the acid is the dominant and most stabilizing factor in the formation of Lewis acid-base adducts, whereas weak interactions are the main thermodynamic driving force (>50 %) for FLPs. Moreover, the ease and extent of structural deformation of the monomers appears to be a key component in the formation of the former type of Lewis pairs. A Natural Orbital for Chemical Valence (NOCV) analysis, which was used to visualize and quantify the charge transfer between the base and the acid, clearly showed the importance and lack of this type of interaction for adducts and FLPs, respectively. The Noncovalent Interaction (NCI) method revealed several kinds of weak interactions between the acid and base components, such as dispersion, π-π stacking, C-Hâ â â π interaction, weak hydrogen bonding, halogen bonding, and weak acid-base interactions, whereas the Quantum Theory of Atoms in Molecules (QTAIM) provided further conceptual insight into strong acid-base interactions.
RESUMEN
In this study, for the first time inverse design was applied to search for the intrinsically most stable radical system in a predefined chemical space of enormous size by scanning in a rational way that entire chemical space. The focus was predominantly on thermodynamic stabilization effects, such as stabilization through resonance. Two different properties were optimized: a newly introduced descriptor called the radical delocalization value and the intrinsic stability via a previously established bond dissociation enthalpy model. The thiadiazinyl radical was chosen as case study of this new approach of inverse design in stable radical chemistry. The resulting optimal structure is found to be highly stable, intrinsically more so than other well-known stable radicals, such as verdazyls and N,N-diphenyl-N'-picrylhydrazyl, and even rivaling the intrinsic stability of nitrogen monoxide.
Asunto(s)
Compuestos de Sulfhidrilo/química , Radicales Libres/síntesis química , Radicales Libres/química , Estructura Molecular , Compuestos de Sulfhidrilo/síntesis química , TermodinámicaRESUMEN
The photocycloaddition reaction of benzene with ethylene has been studied at the CASSCF level, including the characterization of an extended conical intersection seam. We show that the chemical selectivity is, in part, controlled by this extended conical intersection seam and that the shape of the conical intersection seam can be understood in terms of simple VB arguments. Further, the shape and energetics of the asynchronous segment of the conical intersection seam suggest that 1,2 (ortho) and 1,3 (meta) will be the preferred chemical products with similar weight. The 1,4 (para) point on the conical intersection is higher in energy and corresponds to a local maximum on the seam. VB analysis shows that the pairs of VB structures along this asynchronous seam are the same and thus the shape will be determined mainly by steric effects. Synchronous structures on the seam are higher in energy and belong to a different branch of the seam separated by a saddle point on the seam. On S1 we have documented three mechanistic pathways corresponding to transition states (with low barriers) between the reactants and the conical intersection seam: a mixed asynchronous/synchronous [1,2] ortho path, an asynchronous [1,3] meta path, and a synchronous [1,3] meta path.
RESUMEN
The design of molecules with optimal properties is an important challenge in chemistry because of the astronomically large number of possible stable structures that is accessible in chemical space. This obstacle can be overcome through inverse molecular design. In inverse design, one uses the computation of certain indices to design molecules with an optimal target property. In this study, for the first time, inverse design was used to optimize reactivity properties of molecules. Specifically, we optimized the acidity of substituted 2-naphthols, both in the ground and the excited state. Substituted 2-naphthols belong to the class of photoacids, showing enhanced acidity when excited from the singlet ground state to the first singlet excited state. The focus of this work is the ground state. As a measure of acidity, three different properties are optimized: the charge on the hydroxyl hydrogen atom of the acid, the charge on the negatively charged oxygen atom of the conjugate base and the energy difference between acid and conjugate base. Both the practical use of the methodology and the results for ground and excited states are discussed.
Asunto(s)
Técnicas Químicas Combinatorias/métodos , Diseño de Fármacos , Concentración de Iones de Hidrógeno , Modelos Químicos , Naftoles/síntesis química , Simulación por ComputadorRESUMEN
Herein, the effects of an electric field on radicals are investigated for a set of model radicals with varying complexity. An electric field impacts the intrinsic philicity of a radical, as quantified by the global electrophilicity index, ω. The extent of change in philicity depends on the directionality and strength of the applied electric field and the dipole moment and polarizability of the radical.
RESUMEN
We present a validation of computationally efficient density functional-based methods for the reproduction of relative bond dissociation energies of large polyaromatic hydrocarbons. Through the calculation of intrinsic radical stabilities and the computation of spin densities, the extent of delocalization of the unpaired electron in the benzylic radicals is examined. We focus on the influence of the level of theory choice applied for the geometry optimization and the role of van der Waals corrections on thermochemical properties. The dispersion effects mainly influence the energetics, causing a small upward shift of the bond dissociation energies. The long-range corrected CAM-B3LYP functional does not improve the traditional B3LYP results for the geometry description of the large delocalized radicals, however a non-negligible influence was encountered when applied for the energetics. It is reported that the f polarization functions present in the 6-311+G(3df,2p) basis set lead to an erroneous trend when combined with the B2PLYP functional for the computation of the single point energies.