Density functional theory study of a molecular allosteric switch for 2,2′‐bipyridyl‐3,3′‐15‐crown‐5

A classical model of “molecular machine,” which acts as an ON–OFF switch for 2,2′‐bipyridyl‐3,3′‐15‐crown‐5 ( L ), has been theoretically studied. It is highly important to understand the mechanism of this switch. The alkali‐metal cations (Na⁺ and K⁺) and W(CO)₄ fragment are introduced to coordinate with the different active sites of L , respectively. The density functional theory (DFT) method is used for understanding the stereochemical structural natures and thermodynamic properties of all the target molecules at B3LYP/6‐31G(d) and SDD (Stuttgart–Dresden) level, together with the corresponding effective core potential (ECP) for tungsten (W). The fully optimized geometries have been performed with real frequencies, which indicate the minima states. The nucleophilicity of L has been investigated by the Fukui functions. The natural bond orbital analysis is used to study the intermolecular charge‐transfer interactions and explore the origin of the internal forces of the molecular switch. In addition, the binding energies, enthalpies, Gibbs free energies, and the cation exchange energies have been studied for L , W(CO)₄ L , and their corresponding complexes. The properties of the complexes displayed by in presence or absence of the W(CO)₄ fragment are also analyzed. The calculated results of allosterism displayed by L are in a good agreement with the experimental results. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011     

Thermal Ammonia Activation by Cationic Transition‐Metal Hydrides of the First Row – Small but Mighty

The thermal reactions of cationic 3d transition‐metal hydrides MH⁺ (M=Sc–Zn, except V and Cu) with ammonia have been studied by gas‐phase experiments and computational methods. There are three primary reaction channels: 1) H₂ elimination by N? H bond activation, 2) ligand exchange under the formation of M(NH₃)⁺, and 3) proton transfer to yield NH₄⁺. Computational studies of these three reaction channels have been performed for the couples MH⁺/NH₃ (M=Sc–Zn) to elucidate mechanistic aspects and characteristic reaction patterns of the first row. For N? H activation, σ‐bond metathesis was found to be operative.     

Breaking and Making of Carbon–Carbon Bonds by Lanthanides and Third‐Row Transition Metals

Carbon‐atom extrusion from the ipso‐position of a halobenzene ring (C₆H₅X; X=F, Cl, Br, I) and its coupling with a methylene ligand to produce acetylene is not confined to [LaCH₂]⁺; also, the third‐row transition‐metal complexes [MCH₂]⁺, M=Hf, Ta, W, Re, and Os, bring about this unusual transformation. However, substrates with substituents X=CN, NO₂, OCH₃, and CF₃ are either not reactive at all or give rise to different products when reacted with [LaCH₂]⁺. In the thermal gas‐phase processes of atomic Ln⁺ with C₇H₇Cl substrates, only those lanthanides with a promotion energy small enough to attain a 4fⁿ5d¹6s¹ configuration are reactive and form both [LnCl]⁺ and [LnC₅H₅Cl]⁺. Branching ratios and the reaction efficiencies of the various processes seem to correlate with molecular properties, like the bond‐dissociation energies of the C?X or M⁺?X bonds or the promotion energies of lanthanides.     

Gas‐phase synthesis of hydrodiphenylcyclopropenylium via nonclassical Favorskii rearrangement from alkali‐cationized α,α′‐dibromodibenzyl ketone

The gas‐phase synthesis of hydrodiphenylcyclopropenylium from alkali‐cationized α,α′‐dibromodibenzyl ketone (1) via nonclassical Lewis‐acid‐induced Favorskii rearrangement has been studied by electrospray ionization/tandem mass spectrometry (ESI‐MS/MS) and theoretical methods, showing that cations [1–Br]⁺ by debromination from 1 and 1 · M⁺(M = Li or Na) by alkali‐metal cationization of 1 could convert into the protonated diphenylcyclopropenone 2 · H⁺ by collision‐induced dissociation in the gas phase. A concerted mechanism for the Lewis‐acid‐induced Favorskii rearrangement from alkali‐metal‐cationized α,α′‐dibromodibenzyl ketone was proposed and studied, based on mass spectrometric results and theoretical methods. Copyright © 2010 John Wiley & Sons, Ltd.     

Gas‐phase fragmentation reactions of protonated benzofuran‐ and dihydrobenzofuran‐type neolignans investigated by accurate‐mass electrospray ionization tandem mass spectrometry

We have investigated gas‐phase fragmentation reactions of protonated benzofuran neolignans (BNs) and dihydrobenzofuran neolignans (DBNs) by accurate‐mass electrospray ionization tandem and multiple‐stage (MSⁿ) mass spectrometry combined with thermochemical data estimated by Computational Chemistry. Most of the protonated compounds fragment into product ions B ([M + H–MeOH]⁺), C ([ B –MeOH]⁺), D ([ C –CO]⁺), and E ([ D –CO]⁺) upon collision‐induced dissociation (CID). However, we identified a series of diagnostic ions and associated them with specific structural features. In the case of compounds displaying an acetoxy group at C‐4, product ion C produces diagnostic ions K ([ C –C₂H₂O]⁺), L ([ K –CO]⁺), and P ([ L –CO]⁺). Formation of product ions H ([ D –H₂O]⁺) and M ([ H –CO]⁺) is associated with the hydroxyl group at C‐3 and C‐3′, whereas product ions N ([ D –MeOH]⁺) and O ([ N –MeOH]⁺) indicate a methoxyl group at the same positions. Finally, product ions F ([ A –C₂H₂O]⁺), Q ([ A –C₃H₆O₂]⁺), I ([ A –C₆H₆O]⁺), and J ([ I –MeOH]⁺) for DBNs and product ion G ([ B –C₂H₂O]⁺) for BNs diagnose a saturated bond between C‐7′ and C‐8′. We used these structure‐fragmentation relationships in combination with deuterium exchange experiments, MSⁿ data, and Computational Chemistry to elucidate the gas‐phase fragmentation pathways of these compounds. These results could help to elucidate DBN and BN metabolites in in vivo and in vitro studies on the basis of electrospray ionization ESI‐CID‐MS/MS data only.     

Evaluation of DFT Methods and Implicit Solvation Models for Anion‐Binding Host‐Guest Systems

Although supramolecular chemistry is traditionally an experimental discipline, computations have emerged as important tools for the understanding of supramolecules. We have explored how well commonly used density functional theory quantum mechanics and polarizable continuum solvation models can calculate binding affinities of host‐guest systems. We report the calculation of binding affinities for eight host–guest complexes and compare our results to experimentally measured binding free energies that span the range from ?2.3 to ?6.1 kcal mol^?1. These systems consist of four hosts (biotin[6]uril, triphenoxymethane, cryptand, and bis‐thiourea) with different halide ions (F^?, Cl^?, Br^?) in various media including organic and aqueous. The mean average deviation (MAD) of calculated from measured ΔG_a is 2.5 kcal mol^?1 when using B3LYP‐D3 with either CPCM or PCM. This MAD value lowers even more by eliminating two outliers: 1.1 kcal mol^?1 for CPCM and 1.2 kcal mol^?1 for PCM. The best DFT and implicit solvation model combination that we have studied is B3LYP?D3 with either CPCM or PCM.     

Density functional theory study of calix[4]arene‐N‐azacrown‐5, calix[4]arene‐N‐phenyl‐azacrown‐5, and their complexes with alkali‐metal cations: Na+, K+, and Rb+

Theoretical studies of 1,3‐alternate‐25,27‐bis(1‐methoxyethyl)calix[4]arene‐azacrown‐5 ( L₁ ), 1,3‐alternate‐25,27‐bis(1‐methoxyethyl)calix[4]arene‐N‐phenyl‐azacrown‐5 ( L₂ ), and the corresponding complexes M⁺/ L of L₁ and L₂ with the alkali‐metal cations: Na⁺, K⁺, and Rb⁺ have been performed using density functional theory (DFT) at B3LYP/6‐31G* level. The optimized geometric structures obtained from DFT calculations are used to perform natural bond orbital (NBO) analysis. The two main types of driving force metal–ligand and cation–π interactions are investigated. The results indicate that intermolecular electrostatic interactions are dominant and the electron‐donating oxygen offer lone pair electrons to the contacting RY* (1‐center Rydberg) or LP* (1‐center valence antibond lone pair) orbitals of M⁺ (Na⁺, K⁺, and Rb⁺). What's more, the cation–π interactions between the metal ion and π‐orbitals of the two rotated benzene rings play a minor role. For all the structures, the most pronounced changes in geometric parameters upon interaction are observed in the calix[4]arene molecule. In addition, an extra pendant phenyl group attached to nitrogen can promote metal complexation by 3D encapsulation greatly. In addition, the enthalpies of complexation reaction and hydrated cation exchange reaction had been studied by the calculated thermodynamic data. The calculated results of hydrated cation exchange reaction are in a good agreement with the experimental data for the complexes. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

Catalytic CO Oxidation by O2 Mediated by Noble‐Metal‐Free Cluster Anions Cu2VO3–5−

Catalytic CO oxidation by molecular O₂ is an important model reaction in both the condensed phase and gas‐phase studies. Available gas‐phase studies indicate that noble metal is indispensable in catalytic CO oxidation by O₂ under thermal collision conditions. Herein, we identified the first example of noble‐metal‐free heteronuclear oxide cluster catalysts, the copper–vanadium bimetallic oxide clusters Cu₂VO_3–5^? for CO oxidation by O₂. The reactions were characterized by mass spectrometry, photoelectron spectroscopy, and density functional calculations. The dynamic nature of the Cu?Cu unit in terms of the electron storage and release is the driving force to promote CO oxidation and O₂ activation during the catalysis.     

Efficient Room‐Temperature Methane Activation by the Closed‐Shell,Metal‐Free Cluster [OSiOH]+: A Novel Mechanistic Variant

The closed‐shell cluster ion [OSiOH]⁺ is generated in the gas phase and its reactivity towards the thermal activation of CH₄ has been examined using Fourier transform‐ion cyclotron resonance (FT‐ICR) mass spectrometry in conjunction with state‐of‐the‐art quantum chemical calculations. Quite unexpectedly at room temperature, [OSiOH]⁺ efficiently mediates C?H bond activation, giving rise to [SiOH]⁺ and [SiOCH₃]⁺ with the concomitant formation of methanol and water, respectively. Mechanistic aspects for this unprecedented reactivity pattern are presented, and the properties of the [OSiOH]⁺/CH₄ couple are compared with those of the closed‐shell systems [OCOH]⁺/CH₄ and [MgOH]⁺/CH₄; the last two couples exhibit an entirely different reactivity scenario.     

Structural connectivity of 18-Crown-6/H+/L-tryptophan noncovalent complexes in gas phase and in solution: Delineating host–guest–solvent interactions in solution from gas phase structures

We investigate the structural correlation of noncovalent crown ether/H⁺/L-tryptophan (CR/TrpH⁺) host–guest complexes in the solution phase with those in the gas phase generated through electrospray ionization/mass spectrometry (ESI/MS) techniques. We perform quantum chemical calculations to determine their structures, relative Gibbs free energies, and infrared spectra. We compare the calculated infrared (IR) spectra with the IR multiphoton dissociation (IRMPD) spectra observed for the 18-Crown-6/TrpH⁺ complex by Polfer and co-workers [J. Phys. Chem. A 2013, 117, 1181–1188] for assigning the IR bands. We observe that the carboxyl group remains “naked,” lacking hydrogen bonding with the CR unit in the gas phase, and that this most stable conformer originates from the corresponding lowest Gibbs free energy structure in solution. Based on these findings, we propose that gas phase host–guest complexes directly correlate with those in solution, reinforcing the possibility of obtaining invaluable information about host–guest–solvent interactions in solution from the structure of the host–guest pair in the gas phase.     

A simple method to estimate relative stabilities of polyethers cationized by alkali metal ions

Dissociation of doubly cationized polyethers, namely [P + 2X]²⁺ into [P + X]⁺ and X⁺, where P = polyethylene glycol (PEG), polypropylene glycol (PPG) and polytetrahydrofuran (PTHF) and X = Na, K and Cs, was studied by means of energy‐dependent collision‐induced dissociation tandem mass spectrometry. It was observed that the collision voltage necessary to obtain 50% fragmentation (CV₅₀) determined for the doubly cationized polyethers of higher degree of polymerization varied linearly with the number of degrees of freedom (DOF) values. This observation allowed us to correlate these slopes with the corresponding relative gas‐phase dissociation energies for binding of alkali ions to polyethers. The relative dissociation energies determined from the corresponding slopes were found to decrease in the order Na⁺ > K⁺ > Cs⁺ for each polyether studied, and an order PPG ≈ PEG > PTHF can be established for each alkali metal ion. Copyright © 2011 John Wiley & Sons, Ltd.     

X‐ray and DFT‐calculated structures of bis[N‐(quinolin‐8‐yl)benzamidato‐κ2N,N′]copper(II)

The application of transition metal chelates as chemotherapeutic agents has the advantage that they can be used as a scaffold around which ligands with DNA recognition elements can be anchored. The facile substitution of these components allows for the DNA recognition and binding properties of the metal chelates to be tuned. Copper is a particularly interesting choice for the development of novel metallodrugs as it is an endogenous metal and is therefore less toxic than other transition metals. The title compound, [Cu(C₁₆H₁₁N₂O)₂], was synthesized by reacting N‐(quinolin‐8‐yl)benzamide and the metal in a 2:1 ratio. Ligand coordination required deprotonation of the amide N—H group and the isolated complex is therefore neutral. The metal ion adopts a flattened tetrahedral coordination geometry with the ligands in a pseudo‐trans configuration. The free rotation afforded by the formal single bond between the amide group and phenyl ring allows the phenyl rings to rotate out‐of‐plane, thus alleviating nonbonded repulsion between the phenyl rings and the quinolyl groups within the complex. Weak C—H…O interactions stabilize a dimer in the solid state. Density functional theory (DFT) simulations at the PBE/6‐311G(dp) level of theory show that the solid‐state structure (C1 symmetry) is 79.33 kJ mol⁻¹ higher in energy than the lowest energy gas‐phase structure (C2 symmetry). Natural bond orbital (NBO) analysis offers an explanation for the formation of the C—H…O interactions in electrostatic terms, but the stabilizing effect is insufficient to support the dimer in the gas phase.     

Encapsulation of TCNQ and the Acridinium Ion within a Bisporphyrin Cavity: Synthesis,Structure, and Photophysical and HOMO–LUMO‐Gap‐Mediated Electron‐Transfer Properties

The encapsulation of tetracyanoquinodimethane (TCNQ) and fluorescent probe acridinium ions (AcH⁺) by diethylpyrrole‐bridged bisporphyrin (H₄DEP) was used to investigate the structural and spectroscopic changes within the bisporphyrin cavity upon substrate binding. X‐ray diffraction studies of the bisporphyrin host (H₄DEP) and the encapsulated host–guest complexes (H₄DEP ? TCNQ and [H₄DEP ? AcH]ClO₄) are reported. Negative and positive shifts of the reduction and oxidation potentials, respectively, indicated that it was difficult to reduce/oxidize the encapsulated complexes. The emission intensities of bisporphyrin, upon excitation at 560 nm, were quenched by about 65 % and 95 % in H₄DEP ? TCNQ and [H₄DEP ? AcH]ClO₄, respectively, owing to photoinduced electron transfer from the excited state of the bisporphyrin to TCNQ/AcH⁺; this result was also supported by DFT calculations. Moreover, the fluorescence intensity of encapsulated AcH⁺ (excited at 340 nm) was also remarkably quenched compared to the free ions, owing to photoinduced singlet‐to‐singlet energy transfer from AcH⁺ to bisporphyrin. Thus, AcH⁺ acted as both an acceptor and a donor, depending on which part of the chromophore was excited in the host–guest complex. The electrochemically evaluated HOMO–LUMO gap was 0.71 and 1.42 eV in H₄DEP ? TCNQ and [H₄DEP ? AcH]ClO₄, respectively, whilst the gap was 2.12 eV in H₄DEP. The extremely low HOMO–LUMO gap in H₄DEP ? TCNQ led to facile electron transfer from the host to the guest, which was manifested in the lowering of the CN stretching frequency (in the solid state) in the IR spectra, a strong radical signal in the EPR spectra at 77 K, and also the presence of low‐energy bands in the UV/Vis spectra (in the solution phase). Such an efficient transfer was only possible when the donor and acceptor moieties were in close proximity to one another.     

The influence of hydrophobic amino acid side groups on the acidity of the aromatic imidazole ring of histidine: A theoretical study

In this study we have calculated the acidity constant (pKa) of imidazole ring in Histidine‐Hydrophobic amino acid dipeptides using the quantum chemistry and continuum solvation methods. Density functional theory calculations with the large basis sets are used to determine the Gibbs free energy of deprotonate in the gas and liquid phases. Based on our results ΔG_S values are located between ?69.38 and ?18.82 kcal mol^?1 which are related to His⁺–Gly and His forms, respectively. pKa of the dipeptides in the aqueous phase was obtained from the calculated gas‐phase and solvation free energies through a thermodynamic cycle and the solvation model chemistry of Martin Karplus et al. Solvation effects are treated using a self‐consistent reaction field formalism involving polarized continuum models. According to our calculations pKa values are between 5.50 and 8.19 that are belong to His⁺–ILe and His⁺–Ala forms, respectively. Natural bond orbital analysis of dipeptides reveals that the electron delocalization in imidazole ring is the most effective factor in determination of acidity order for these compounds. Structural analysis confirmed that the orientation of carbonyl group with respect to imidazole ring is an effective factor in imidazole ring stability. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Effect of metal cations [Li+, Na+, K+, Be2+, Mg2+, and Ca2+] on the structure of 2‐(3′‐hydroxy‐2′‐pyridyl)benzoxazole: A theoretical investigation

Density functional theory calculations were performed at the B3LYP/6‐311++G(d,p) level to systematically explore the geometrical multiplicity and binding strength for the complexes formed by alkaline and alkaline earth metal cations, viz. Li⁺, Na⁺, K⁺, Be²⁺, Mg²⁺, and Ca²⁺ (Mⁿ⁺, hereinafter), with 2‐(3′‐hydroxy‐2′‐pyridyl)benzoxazole. A total of 60 initial structures were designed and optimized, of which 51 optimized structures were found, which could be divided into two different types: monodentate complexes and bidentate complexes. In the cation‐heteroatom complex, bidentate binding is generally stronger than monodentate binding, and of which the bidentate binding with five‐membered ring structure has the strongest interaction. Energy decomposition revealed that the total binding energies mainly come from electrostatic interaction for alkaline metal ion complexes and orbital interaction energy for alkaline earth metal ion complex. In addition, the electron localization function analysis show that only the Be? O and Be? N bond are covalent character, and others are ionic character. © 2012 Wiley Periodicals, Inc.     

Gas‐phase reaction mechanism of Pd+ with CH3CHO: A density functional theoretical study

Details on the reactions of: (1) Pd⁺ + CH₃CHO → PdCO⁺ + CH₄ and (2) Pd⁺ + CH₃CHO → PdH + CH₃CO⁺ in the gas phase were investigated using density functional theory (B3LYP), in conjunction with the LANL2DZ+6‐311+G(d) basis set. Three encounter complexes were located on the potential energy surfaces and the calculations indicated that both the C? C and aldehyde C? H bond activation of acetaldehyde could lead to the dominant demethanation reaction. The charge transfer process for PdH abstraction was caused by an intramolecular PdH rearrangement of the newly found η¹‐aldehyde attached complex. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Investigation of activation energies for dissociation of host‐guest complexes in the gas phase using low‐energy collision induced dissociation

A low‐energy collision induced dissociation (CID) (low‐energy CID) approach that can determine both activation energy and activation entropy has been used to evaluate gas‐phase binding energies of host‐guest (H‐G) complexes of a heteroditopic hemicryptophane cage host (Zn (II)@1) with a series of biologically relevant guests. In order to use this approach, preliminary calibration of the effective temperature of ions undergoing resonance excitation is required. This was accomplished by employing blackbody infrared radiative dissociation (BIRD) which allows direct measurement of activation parameters. Activation energies and pre‐exponential factors were evaluated for more than 10 H‐G complexes via the use of low‐energy CID. The relatively long residence time of the ions inside the linear ion trap (maximum of 60 s) allowed the study of dissociations with rates below 1 s^?1. This possibility, along with the large size of the investigated ions, ensures the fulfilment of rapid energy exchange (REX) conditions and, as a consequence, accurate application of the Arrhenius equation. Compared with the BIRD technique, low‐energy CID allows access to higher effective temperatures, thereby permitting one to probe more endothermic decomposition pathways. Based on the measured activation parameters, guests bearing a phosphate (―OPO₃^2?) functional group were found to bind more strongly with the encapsulating cage than those having a sulfonate (―SO₃^?) group; however, the latter ones make stronger bonds than those with a carboxylate (―CO₂^?) group. In addition, it was observed that the presence of trimethylammonium (―N(CH₃)₃⁺) or phenyl groups in the guest's structure improves the strength of H‐G interactions. The use of this technique is very straightforward, and it does not require any instrumental modifications. Thus, it can be applied to other H‐G chemistry studies where comparison of bond dissociation energies is of paramount importance.     

Gas‐Phase Chemistry of Ethynylamine, ‐Phosphine and ‐Arsine. Structure and Stability of their Cu+ and Ni+ Complexes

The Cu⁺ and Ni⁺ binding energies of ethynylamine, ethynylphosphine and ethynylarsine have been calculated at the B3LYP/6‐311+G(2df,2p)//B3LYP/6‐311G(d,p) level of theory. Significant differences between nitrogen‐containing and phosphorus‐ or arsenic‐containing compounds have been found regarding structural effects upon metal cation association. While for ethynylamine the global minimum of the potential energy surface corresponds to the complex in which the metal cation binds to the β‐carbon, for ethynylphosphine the most favourable process corresponds to phosphorus attachment. For ethynylarsine, the conventional π‐complex is the most stable one. This behavior resembles that found for the corresponding vinyl analogues, with the only exception being the arsenic derivative. The calculated Cu⁺ and Ni⁺ binding energies for attachment to the heteroatom follow a different trend, P>As>N, to that predicted for the corresponding proton affinities, P>N>As. Cu⁺ and Ni⁺ binding energies are almost identical when the metal cation binds to the heteroatom. However, Ni⁺ binding energies are slightly larger than Cu⁺ binding energies when the metal cation interacts with the C?C bond.     

Ortho‐hydroxyl effect and proton transfer via ion–neutral complex: the fragmentation study of protonated imine resveratrol analogues in mass spectrometry

The fragmentation pathways of protonated imine resveratrol analogues in the gas‐phase were investigated by electrospray ionization–tandem mass spectrometry. Benzyl cations were formed in the imine resveratrol analogues that had an ortho‐hydroxyl group on the benzene ring A. The specific elimination of the quinomethane neutral, CH₂ = C₆H₄ = O, from the two isomeric ions [M1 + H]⁺ and [M3 + H]⁺ via the corresponding ion–neutral complexes was observed. The fragmentation pathway for the related meta‐isomer, ion [M2 + H]⁺ and the other congeners was not observed. Accurate mass measurements and additional experiments carried out with a chlorinated analogue and the trideuterated isotopolog of M1 supported the overall interpretation of the fragmentation phenomena observed. It is very helpful for understanding the intriguing roles of ortho‐hydroxyl effect and ion–neutral complexes in fragmentation reactions and enriching the knowledge of the gas‐phase chemistry of the benzyl cation. Copyright © 2016 John Wiley & Sons, Ltd.