Density functional theory study of crown ether-magnesium complexes: from a solvated ion to an ion trap.

Metal ion detection rests on host-guest recognition. We propose a theoretical protocol for designing an optimal trap for a desired metal cation. A host for magnesium ions was sought for among derivatives of crown ethers 12-crown-4, 15-crown-5, and 18-crown-6. Mg-crown complexes and their hydrated counterparts with water molecules bound to the cation were optimized using density functional theory. Based on specific geometric criteria, Interacting quantum atoms analysis and density functional theory-based molecular dynamics of Mg-crown complexes immersed in water, crown ethers for optimal accommodation of Mg2+ in aqueous solution were identified. Selectivity of the chosen crowns towards Na+, K+, and Ca2+ ions is addressed.

Carbodiphosphorane-Stabilized Parent Dioxophosphorane: A Valuable Synthetic HO2P Source.

Introducing a small phosphorus-based fragment into other molecular entities via, for example, phosphorylation/phosphonylation is an important process in synthetic chemistry. One of the approaches to achieve this is by trapping and subsequently releasing extremely reactive phosphorus-based molecules such as dioxophosphoranes. In this work, electron-rich hexaphenylcarbodiphosphorane (CDP) was used to stabilize the least thermodynamically favorable isomer of HO2P to yield monomeric CDP·PHO2. The title compound was observed to be a quite versatile phosphonylating agent; that is, it showed a great ability to transfer, for the first time, the HPO2 fragment to a number of substrates such as alcohols, amines, carboxylic acids, and water. Several phosphorous-based compounds that were generated using this synthetic approach were also isolated and characterized for the first time. According to the initial computational studies, the addition-elimination pathway was significantly more favorable than the corresponding elimination-addition route for "delivering" the HO2P unit in these reactions.

Proton leap: shuttling of protons onto benzonitrile.

The detailed description of chemical transformations in the interstellar medium allows deciphering the origin of a number of small and medium - sized organic molecules. We present density functional theory analysis of proton transfer from the trihydrogen cation and the ethenium cation to benzonitrile, a recently discovered species in the Taurus Molecular Cloud 1. Detailed energy transformations along the reaction paths were analyzed using the interacting quantum atoms methodology, which elucidated how the proton carrier influences the lightness to deliver the proton to benzonitrile's nitrogen atom. The proton carriers' deformation energy represents the largest destabilizing effect, whereas a proton's promotion energy, the benzonitrile-proton Coulomb attraction, as well as non-classical benzonitrile-proton and carrier-proton interaction are the dominant stabilizing energy components. As two ion-molecule reactions proceed without energy barriers, rate constants were estimated using the classical capture theory and were found to be an order of magnitude larger for the reaction with the trihydrogen cation compared to that with the ethenium cation (∼10-8 and 10-9 cm3 s-1, respectively). These results were obtained both with quantum chemical and ab initio molecular dynamics simulations (the latter performed at 10 K and 100 K), confirming that up to 100 K both systems choose energetically undemanding routes by tracking the corresponding minimum energy paths. A concept of a turning point is introduced, which is an equivalent to the transition state in barrierless reactions.

The significance of the metal cation in guanine-quartet - metalloporphyrin complexes.

The planarity and the appropriate size of the porphyrin ring make porphyrin derivatives ideal ligands for stacking to guanine quartets and they could thus be used as anti-cancer drugs. In this contribution we analyzed complexes of a guanine quartet with a porphyrin molecule, magnesium porphyrin and calcium porphyrin. As magnesium and calcium ions are located in the center and above the porphyrin ring, respectively, the two metalloporphyrins are expected to have different impacts on the target. The optimized structures of the three systems revealed geometrical changes in the guanine quartet upon complexation: while stacking of porphyrin and magnesium porphyrin does not induce significant changes, calcium porphyrin considerably distorts the quartet's structure, which has significant implications for the binding properties among guanine molecules. Ab initio molecular dynamics simulations revealed that the systems perform small fluctuations around the equilibrium structures. The largest atom displacements are performed by the calcium ion. The interacting quantum atoms methodology enabled analysis of the binding properties in the studied complexes. Interestingly, although the proximity of the calcium ion is responsible for the quartet's pronounced deformation and weakening of guanine-guanine binding, it also enables stronger binding of the metal ion to the quartet, resulting in a more stable complex. These results imply that metalloporphyrin-like ligands with out-of-plane central ions might represent promising drug candidates in anti-tumor treatment.

Modulating Excited Charge-Transfer States of G-Quartet Self-Assemblies by Earth Alkaline Cations and Hydration.

Guanine self-assemblies are promising supramolecular platforms for optoelectronic applications. The study (Hua et al., J. Phys. Chem. C 2012, 116, 14,682-14,689) reported that alkaline cations cannot modulate the electronic absorption spectrum of G-quadruplexes, although a cation effect is observable during electronic relaxation due to different mobility of Na+ and K+ cations. In this work, we theoretically examined whether divalent Mg2+ and Ca2+ cations and hydration might shift excited charge-transfer states of a cation-templated stacked G-quartet to the absorption red tail. Our results showed that earth alkaline cations blue-shifted nπ* states and stabilized charge-transfer ππ* states relative to those of complexes with alkaline cations, although the number of charge-separation states was not significantly modified. Earth alkaline cations were not able to considerably increase the amount of charge-transfer states below the Lb excitonic states. Hydration shifted charge-transfer states of the Na+-coordinated G-octet to the absorption red tail, although this part of the spectrum was still dominated by monomer-like excitations. We found G-octet electron detachment states at low excitation energies in aqueous solution. These states were distributed over a broad range of excitation energies and could be responsible for oxidative damage observed upon UV irradiation of biological G-quadruplexes.

Elucidating Solvent Effects on Strong Intramolecular Hydrogen Bond: DFT-MD Study of Dibenzoylmethane in Methanol Solution.

The dynamic aspect of solvation plays a crucial role in determining properties of strong intramolecular hydrogen bonds since solvent fluctuations modify instantaneous hydrogen-bonded proton transfer barriers. Previous studies pointed out that solvent-solute interactions in the first solvation shell govern the position of the proton but the ability of the electric field due to other solvent molecules to localize the proton remains an important issue. In this work, we examine the structure of the O-H⋅⋅⋅O intramolecular hydrogen bond of dibenzoylmethane in methanol solution by employing density functional theory-based molecular dynamics and quantum chemical calculations. Our computations showed that homogeneous electric fields with intensities corresponding to those found in polar solvents are able to considerably alter the proton transfer barrier height in the gas phase. In methanol solution, the proton position is correlated with the difference in electrostatic potentials on the oxygen atoms of dibenzoylmethane even when dibenzoylmethane-methanol hydrogen bonding is lacking. On a timescale of our simulation, the hydrogen bonding and solvent electrostatics tend to localize the proton on different oxygen atoms. These findings provide an insight into the importance of the solvent electric field on the structure of a strong intramolecular hydrogen bond.

When hydroquinone meets methoxy radical: Hydrogen abstraction reaction from the viewpoint of interacting quantum atoms.

Interacting Quantum Atoms methodology is used for a detailed analysis of hydrogen abstraction reaction from hydroquinone by methoxy radical. Two pathways are analyzed, which differ in the orientation of the reactants at the corresponding transition states. Although the discrepancy between the two barriers amounts to only 2 kJ/mol, which implies that the two pathways are of comparable probability, the extent of intra-atomic and inter-atomic energy changes differs considerably. We thus demonstrated that Interacting Quantum Atoms procedure can be applied to unravel distinct energy transfer routes in seemingly similar mechanisms. Identification of energy components with the greatest contribution to the variation of the overall energy (intra-atomic and inter-atomic terms that involve hydroquinone's oxygen and the carbon atom covalently bound to it, the transferring hydrogen and methoxy radical's oxygen), is performed using the Relative energy gradient method. Additionally, the Interacting Quantum Fragments approach shed light on the nature of dominant interactions among selected fragments: both Coulomb and exchange-correlation contributions are of comparable importance when considering interactions of the transferring hydrogen atom with all other atoms, whereas the exchange-correlation term dominates interaction between methoxy radical's methyl group and hydroquinone's aromatic ring. This study represents one of the first applications of Interacting Quantum Fragments approach on first order saddle points. © 2018 Wiley Periodicals, Inc.

E-H (E = B, Si, C) Bond Activation by Tuning Structural and Electronic Properties of Phosphenium Cations.

In this work, strategic enhancement of electrophilicity of phosphenium cations for the purpose of small-molecule activation was described. Our synthetic methodology for generation of novel two-coordinate phosphorus(III)-based compounds [{C6H4(MeN)2C}2C·PR]2+ ([2a]2+, R = NiPr2; [2b]2+, R = Ph) was based on the exceptional electron-donating properties of the carbodicarbene ligand (CDC). The effects of P-centered substituent exchange and increase in the overall positive charge on small substrate activation were comparatively determined by incorporating the bis(amino)phosphenium ion [(iPr2N)2P]+ ([1]+) in this study. Implemented structural and electronic modifications of phosphenium salts were computationally verified and subsequently confirmed by isolation and characterization of the corresponding E-H (E = B, Si, C) bond activation products. While both phosphenium mono- and dications oxidatively inserted/cleaved the B-H bond of Lewis base stabilized boranes, the increased electrophilicity of doubly charged species also afforded the activation of significantly less hydridic Si-H and C-H bonds. The preference of [2a]2+ and [2b]2+ to abstract the hydride rather than to insert into the corresponding bond of silanes, as well as the formation of the carbodicarbene-stabilized parent phosphenium ion [{C6H4(MeN)2C}2C·PH2]+ ([2·PH2]+) were experimentally validated.

A new insight into the photochemistry of avobenzone in gas phase and acetonitrile from ab initio calculations.

Avobenzone (4-tert-butyl-4'-methoxydibenzoylmethane, AB) is one of the most widely used filters in sunscreens for skin photoprotection in the UVA band. The photochemistry of AB includes keto-enol tautomerization, cis-trans isomerization, rotation about the single bond and α bond cleavages of carbonyl groups. In this contribution we study chelated and non-chelated enol, rotamers Z and E, and keto tautomers of AB in the ground and excited states in gas phase and acetonitrile by means of a coupled cluster method. Our findings suggest that torsion around the double C2-C3 bond of photoexcited chelated enol leads to internal conversion to the ground state and formation of rotamer E. In addition, opening of the chelated hydrogen ring by torsion of the hydroxyl group creates non-chelated enol. The possible mechanisms of rotamer Z formation are discussed. The solvent dependent photolability is related to the relative order of the lowest triplet ππ* and nπ* states of the keto tautomer.

Stability and Anharmonic N-H Stretching Frequencies of 1-Methylthymine Dimers: Hydrogen Bonding versus π-Stacking.

Stability of three hydrogen-bonded and six stacked 1-methylthymine (1 mT) dimers was studied with the DFT-D3 method at various temperatures. It was demonstrated that the stacked dimers are slightly less stable than the hydrogen-bonded counterparts. Existence of T-shaped dimers is addressed. Anharmonic couplings that involve N-H stretching modes of the nine species are studied. Surprisingly, we find that N-H stretching modes of the two 1 mT molecules are significantly coupled in four stacked dimers. The presented results shed light on existence of strong mode couplings between the two N-H stretching modes in stacked aromatic species. Our calculations support the proposal ( J. Phys. Chem. A 2011 , 115 , 9429 - 9439 ) that presence of several dimers is responsible for appearance of wide and structured bands in 1 mT homodimers' jet-cooled spectra above 2900 cm(-1).

Using Density Functional Theory To Study Neutral and Ionized Stacked Thymine Dimers.

Stacking interactions in thymine dimers are studied with density functional theory. According to our calculations, six dimers of comparable stability can be prepared at low temperature, but dimerization is impossible at room temperature due to the large entropy contribution that accompanies it. Analysis of vibrational anharmonic coupling terms shows that each of the dimers exhibits distinct vibrational dynamics. Properties of electron density in the intermolecular region are used to analyze neutral stacked species and their ionized forms. Bond paths and critical points in the intermolecular region are identified, but a simple relationship between binding energy and total electron density in the intermolecular critical points could not be found due to an uneven electron distribution in the binding region. The reduced density gradient was confirmed to be a useful tool for analysis of weak stacking interactions. Those interactions also affect vertical and adiabatic ionization energies, which are computed to be slightly lower for the dimers compared to the monomer.

Oxidation of a P-C Bond under Mild Conditions.

The reactivity of phosphenium dication [(Ph3P)2C-P-NiPr2](2+), 1(2+), towards pyridine N-oxide (O-py) has been investigated. The resulting oxophosphonium dication [(Ph3P)2C(NiPr2)P(O)(O-py)](2+), 2(2+), was surprisingly stabilized by a less nucleophilic O-py ligand instead of pyridine (py). This compound was then identified as an analogue of the elusive Criegee intermediate as it underwent oxygen insertion into the P-C bond through a mechanism usually observed for Baeyer-Villiger oxidations. This oxygen insertion appears to be the first example of a Baeyer-Villiger oxidation involving O-py.

Association between systemic non-criteria APS manifestations and antibody type and level: results from the Serbian national cohort study.

OBJECTIVES: The aim of this study was to investigate the importance of aPL type and level for non-criteria-related events in APS patients. METHODS: Our study included 374 patients: 260 with PAPS and 114 with APS associated with systemic lupus erythematosus (SLE). RESULTS: We discovered significant connection between migraine and LA absence, livedo reticularis and aCL-IgG, skin ulcerations with aCL-IgG and anti-ß2GPI-IgM, pseudovasculitis lesions with aCL-IgG, aCL-IgM and anti-ß2GPI-IgM, and thrombocytopenia with aCL-IgM, aCL-IgG and anti-ß2GPI-IgG. Thrombocytopenia occurred more frequently in patients with more than one aPL. In PAPS, epilepsy correlated with ß2GPI-IgM, migraine with aCL-IgM, and thrombocytopenia with aCL-IgM, aCL-IgG, anti ß2GPI-IgG and LA. Skin ulcerations occurred more frequently in IIc category patients and in patients with high levels of aCL-IgG and anti ß2GPI-IgG. Livedo reticularis was more prominent in PAPS with high levels of aCL-IgG. Significantly higher prevalence of thrombocytopenia was observed in patients with high levels of aCL-IgG and anti ß2GPI-IgG. Epilepsy was related to high levels of anti ß2GPI-IgM and thrombocytopenia in the SAPS was correlated with aCL-IgG. Skin ulcerations were more prevalent in aCL-IgM positive SAPS patients and epilepsy more frequently in SAPS patients with high levels of anti ß2GPI-IgG. CONCLUSIONS: Our study showed that certain aPL type with certain level correlated with non-criteria manifestations, suggesting their predictive role.

Vibrational spectroscopy of picolinamide and water: from dimers to condensed phase.

Because of the presence of polar groups in picolinamide, its aqueous solvation is characterized by formation of multiple hydrogen bonds, which are responsible for differences in vibrational spectra of picolinamide in the gas phase and its aqueous solution. In this contribution, we try to identify dominant interactions between the solute and the solvent molecules that are the origin of the observed spectral changes. For this purpose, we analyzed the vibrational properties of picolinamide (a single molecule and also embedded in the environment described with an implicit solvent model) and picolinamide-water dimers: by comparing their vibrational frequencies with experimentally observed values of picolinamides' aqueous solution and by analyzing the computed anharmonic force constants, it is possible to recognize whether and in which way the solvent causes changes in the vibrational properties of the title compound. Calculations performed on the picolinamide three-hydrate confirm conclusions obtained by analyzing monohydrates.

O-H stretch in phenol and its hydrogen-bonded complexes: band position and relaxation pathways.

Anharmonic force fields are a suitable means for identification of vibrational degrees of freedom responsible for the peculiar shape of molecular spectra and the existence of diverse relaxation pathways. In this contribution, we investigated interactions that govern the position of the O-H stretching band in phenol and its dimers with water and ammonia. Dominant couplings are identified, and the nature of relaxation channels is analyzed. The effect of hydrogen bonding on O-H stretching motion and vibrational energy redistribution time through intra- and intermolecular interactions is studied, and possible vibrational predissociation upon O-H stretch excitation is addressed. The results based on computed anharmonic force constants are in accord with the available experimental findings.

Alkaline earth cations binding mode tailors excited-state charge transfer properties of guanine quadruplex: A TDDFT study.

Quadruplexes formed by nucleic acids and their derivates tend to chelate different monovalent and bivalent cations, which simultaneously affect their excited electronic states properties. Cation binding to every and every other cavity of the central ion channel could be exploited for tuning exited-state charge transfer properties. In this work we utilize set of descriptors constructed on the basis of the one-electron transition density matrix obtained using linear-response TDDFT to study excited states properties of four crystallized tetramolecular quadruplexes that chelate alkaline earth cations (Ca2+, Sr2+ and Ba2+). Here, we show that alkaline earth cations situated at adjacent vacancies promote existence of the nucleobase-metal charge separation (CS) states, contrary to the structures with cations that occupy every second available vacancy. We argued that stabilization of these CS states is due to the strong electric field that stabilizes d orbitals of the cations which accept an excited-electron. Moreover, CS content is increased and redshifted below the first bright transition when number of the chelated cations is increased. Hydration effects stabilized CS states and increased their relative content. We also identified electron detachment states in the broad energy range for the Ca2+ containing system. These findings are valuable for understanding and development of the novel nanostructures based on the quadruplex scaffold with adjustable optical properties.

Water-Mediated Interactions Enhance Alkaline Earth Cation Chelation in Neighboring Cavities of a Cytosine Quartet in the DNA Quadruplex.

Larger Coulombic repulsion between divalent cations compared to the monovalent counterparts dictates the cation-cation distance in the central ion channel of quadruplexes. In this work, density functional theory and a continuum solvation model were employed to study bond energies of alkaline earth cations in adjacent cavities of the central ion channel. Four crystallized tetramolecular quadruplexes with various geometric constraints and structural motifs available in the Protein Data Bank were examined in order to understand how the cation binding affinities could be increased in aqueous solution. A cytosine quartet sandwiched between guanine quartets has a larger bond energy of the second alkaline earth cation in comparison with guanine and uracil quartets. Four highly conserved hydrogen-bonded water molecules in the center of the cytosine quartet are responsible for a higher electrostatic interaction with the cations in comparison with guanines' carbonyl groups. The reported findings are valuable for the design of synthetic quadruplexes templated with divalent cations for optoelectronic applications.

Intriguing Intermolecular Interplay in Guanine Quartet Complexes with Alkali and Alkaline Earth Cations.

The possibility to target noncanonical guanine structures with specific ligands for therapeutic purposes inspired numerous theoretical and experimental investigations of a guanine quartet and its stacked composites. In this work, we employed the interacting quantum atoms methodology to study interactions among different fragments in complexes composed of a guanine quartet and alkali (Li+, Na+, K+) or alkaline earth (Be2+, Mg2+, Ca2+) cations in vacuo: metal-quartet interaction, influence of the cation on guanine-guanine interaction, as well as hydrogen bond cooperativity in the guanine quartet and its complexes with metal ions. Interestingly, although the presence of a cation intensifies interaction among guanine molecules, it lowers their binding energy because of notable quartet's distortion which is responsible for guanines' substantial deformation energy. This phenomenon is particularly pronounced with Be2+ which, out of the six analyzed cations, enhances hydrogen bond cooperativity to the greatest extent.

New Insight into Uracil Stacking in Water from ab Initio Molecular Dynamics.

Nucleobases spontaneously aggregate in water by forming stacked dimers and multimers. It is assumed that the main contributions to the aggregation stem from hydrophobic and base-base dispersion interactions. By studying the uracil monomer and dimer in bulk water with the first principle molecular dynamics, we discuss dimer structure and provide evidence that stacking increases the uracil-water hydrogen bonding strength and alters the hydration structure of uracil. These changes have a significant influence on the intensity and shift of the carbonyl stretching band as revealed by simulated infrared absorption spectra of the monomer and dimer and available experimental spectra. The contributions of dipole-dipole, dispersion, and water mediated forces to the stacking are discussed. The reported findings are valuable for understanding the microscopic mechanism of heteroaromatic association in water which is relevant to a large range of chemical and biological systems.

Bis(carbodicarbene)phosphenium trication: the case against hypervalency.

The first example of a phosphenium trication has been prepared by using the exceptional nucleophilic properties of a carbodicarbene ligand. According to theoretical investigations the trication contains quite polarized P-C bonds suggesting a substantial contribution from the dative bond model. As one of the resonance forms for the title compound depicted a hypervalent phosphoranide we also showed that phosphoranides, in general, do not contain a hypervalent P centre.