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.

A dual attack on the peroxide bond. The common principle of peroxidatic cysteine or selenocysteine residues.

The (seleno)cysteine residues in some protein families react with hydroperoxides with rate constants far beyond those of fully dissociated low molecular weight thiol or selenol compounds. In case of the glutathione peroxidases, we could demonstrate that high rate constants are achieved by a proton transfer from the chalcogenol to a residue of the active site [Orian et al. Free Radic. Biol. Med. 87 (2015)]. We extended this study to three more protein families (OxyR, GAPDH and Prx). According to DFT calculations, a proton transfer from the active site chalcogenol to a residue within the active site is a prerequisite for both, creating a chalcogenolate that attacks one oxygen of the hydroperoxide substrate and combining the delocalized proton with the remaining OH or OR, respectively, to create an ideal leaving group. The "parking postions" of the delocalized proton differ between the protein families. It is the ring nitrogen of tryptophan in GPx, a histidine in GAPDH and OxyR and a threonine in Prx. The basic principle, however, is common to all four families of proteins. We, thus, conclude that the principle outlined in this investigation offers a convincing explanation for how a cysteine residue can become peroxidatic.

Evidence for a chemical clock in oscillatory formation of UiO-66.

Chemical clocks are often used as exciting classroom experiments, where an induction time is followed by rapidly changing colours that expose oscillating concentration patterns. This type of reaction belongs to a class of nonlinear chemical kinetics also linked to chaos, wave propagation and Turing patterns. Despite its vastness in occurrence and applicability, the clock reaction is only well understood for liquid-state processes. Here we report a chemical clock reaction, in which a solidifying entity, metal-organic framework UiO-66, displays oscillations in crystal dimension and number, as shown by X-ray scattering. In rationalizing this result, we introduce a computational approach, the metal-organic molecular orbital methodology, to pinpoint interaction between the tectonic building blocks that construct the metal-organic framework material. In this way, we show that hydrochloric acid plays the role of autocatalyst, bridging separate processes of condensation and crystallization.

Intercalation of daunomycin into stacked DNA base pairs. DFT study of an anticancer drug.

We have computationally studied the intercalation of the antitumor drug daunomycin into six stacks of Watson-Crick DNA base pairs (i.e., AT-AT, AT-TA, GC-AT, CG-TA, GC-GC, GC-CG) using density functional theory (DFT). The proton affinity of the DNA intercalator daunomycin in water was computed to be 159.2 kcal/mol at BP86/TZ2P, which is in line with the experimental observation that daunomycin is protonated under physiological conditions. The intercalation interaction of protonated daunomycin with two stacked DNA base pairs was studied through a hybrid approach in which intercalation is treated at LDA/TZP while the molecular structure of daunomycin and hydrogen-bonded Watson-Crick pairs is computed at BP86/TZ2P. We find that the affinity of the drug for the six considered base pair dimers decreases in the order AT-AT > AT-TA > GC-AT > GC-TA > GC-CG > GC-GC, in excellent agreement with experimental data on the thermodynamics of the interaction between daunomycin and synthetic polynucleotides in aqueous solution. Our analyses show that the overall stability of the intercalation complexes comes mainly from pi-pi stacking but an important contribution to the computed and experimentally observed sequence specificity comes from hydrogen bonding between daunomycin and hetero atoms in the minor groove of AT base pairs.

Covalent versus ionic bonding in alkalimetal fluoride oligomers.

The most polar bond in chemistry is that between a fluorine and an alkalimetal atom. Inspired by our recent finding that other polar bonds (C--M and H--M) have important covalent contributions (i.e., stabilization due to bond overlap), we herein address the question if covalency is also essential in the F--M bond. Thus, we have theoretically studied the alkalimetal fluoride monomers, FM, and (distorted) cubic tetramers, (FM)4, with M=Li, Na, K, and Rb, using density functional theory at the BP86/TZ2P level. Our objective is to determine how the structure and thermochemistry (e.g., F--M bond lengths and strengths, oligomerization energies, etc.) of alkalimetal fluorides depend on the metal atom, and to understand the emerging trends in terms of quantitative Kohn-Sham molecular orbital theory. The analyses confirm the extreme polarity of the F--M bond (dipole moment, Voronoi deformation density and Hirshfeld atomic charges), and they reveal that bond overlap-derived stabilization (ca. -6, -6, and -2 kcal/mol) contributes only little to the bond strength (-136, -112, and -114 kcal/mol) and the trend therein along Li, Na, and K. According to this and other criteria, the F--M bond is not only strongly polar, but also has a truly ionic bonding mechanism. Interestingly, the polarity is reduced on tetramerization. For the lithium and sodium fluoride tetramers, the F4 tetrahedron is larger than and surrounds the M4 cluster (i.e., F--F>>M--M). But in the potassium and rubidium fluoride tetramers, the F4 tetrahedron is smaller than and inside the M4 cluster (i.e., F--F

Adenine tautomers: relative stabilities, ionization energies, and mismatch with cytosine.

In this study, we have investigated 12 tautomers of the DNA base adenine at the BP86/TZ2P and BP86/QZ4P levels of density functional theory. The vertical and adiabatic ionization energies of all tautomers were determined as the difference in energy between the radical cation and the corresponding neutral system. Furthermore, an evaluation is made for the eigenvalue spectra calculated with the SAOP functional, which is shown to lead to substantial improvements for orbital energies compared to BP86. We have also explored the correlations between the Kohn-Sham orbitals of the different tautomers at the BP86/QZ4P and SAOP/QZ4P levels. Finally, we discuss implications of the existence of the tautomeric forms of adenine for the DNA replication.

High-resolution infrared spectroscopy of the charge-transfer complex [Ar-N2]+: a combined experimental/theoretical study.

A combined experimental and theoretical study of the charge-transfer complex [Ar-N(2)](+) is presented. Nearly 50 transitions split by spin-rotation interaction have been observed by means of infrared diode laser absorption spectroscopy in a supersonic planar plasma expansion. The band origin is at 2272.2563(18) cm(-1) and rotational constants in the ground and vibrationally (NN-stretch) excited state amount to 0.128701(8) cm(-1) and 0.128203(8) cm(-1), respectively. The interpretation of the data in terms of a charge switch upon complexation is supported by new ab initio calculations. The best estimate for a linear equilibrium structure yields R(e)(NN)=1.102 A and R(e)(Ar-N)=2.190 A. Predictions for molecular parameters not directly available from the experimental results are presented as well. Furthermore, the electronic structure and Ar-N bonding mechanism of [Ar-N(2)](+) have been analyzed in detail. The Ar-N bond is a textbook example of a classical 2-center-3-electron bond.

Mapping the sites for selective oxidation of guanines in DNA.

The effective energy of a positive charge when it is localized at a specific guanine nucleobase in DNA was calculated using density functional theory. The results demonstrate that the efficiency of a guanine to act as a hole-trap in DNA strongly depends on the nature of the flanking nucleobases. The presence of a pyrimidine base at the 3' position adjacent to a guanine significantly increases the localization energy of the positive charge. The calculated distributions of a positive charge in sequences of two or three adjacent guanines, flanked by other nucleobases, provide an explanation for experimental literature data on the site-selective oxidation of DNA.

Base-induced 1,4-elimination: insights from theory and mass spectrometry.

Experimental and theoretical studies on gas-phase base-induced 1,4-elimination reactions are summarized and discussed. The emphasis is on the synergy that is achieved by combining the complementary data from mass spectrometry and theoretical chemistry. The scope and applications of 1,4-eliminations are discussed and compared with other elementary reactions; e.g., 1,2-elimination and aliphatic (S(N)2) and allylic (S(N)2') nucleophilic substitution. Furthermore, the syn versus anti stereochemistry of 1,4-elimination reactions and the effect of E versus Z stereochemistry of the substrate are examined. Particular attention is paid to the mechanistic nature of 1,4-elimination, i.e., E2 or E1cb, as well as special features such as the single-well E2 and E1cb mechanism. Also, new results from density functional theory computations (BP86/TZ2P) are presented.

Structure and bonding of transition metal-boryl compounds. Theoretical study of [(PH3)2(CO)ClOs-BR2] and [(PH3)2(CO)2ClOs-BR2] (BR2 = BH2, BF2, B(OH)2, B(OCH=CHO), Bcat).

Quantum chemical DFT calculations using the B3LYP functionals have been carried out for the electronically unsaturated 16 VE five-coordinate osmium boryl-complexes [(PH3)2(CO)ClOs-BR2] and the 18 VE six-coordinate complexes [(PH3)2(CO)2ClOs-BR2] with BR2 = BH2, BF2, B(OH)2, B(OHC=CHO), and Bcat (cat = catecholate O2C6H4). The bonding situation of the Os-BR2 bond was analyzed with the help of the NBO partitioning scheme. The Os-B bond dissociation energies of the 16 VE complexes are very high, and they do not change very much for the different boryl ligands. The 18 VE complexes have only slightly lower bond energies than the 16 VE species. The Os-B bond in both classes of compounds is provided by a covalent sigma-bond which is polarized toward osmium and by strong charge attraction. Os-->B pi-donation is not important for the Os-B binding interactions, except for the Os-BH2 complexes. The stability of the boryl complexes [Os]-BR2 comes mainly from B<--R pi-donation, which is clearly higher than the Os-->B pi-donation. The intraligand charge distribution of the BR2 group changes little when the Os-B bond is formed, except for BH2. The CO ligand in [(PH3)2(CO)2ClOs-BR2] which is trans to BR2 has a relatively weak bond to the osmium atom.