Hydroxyl radicals in ice: insights into local structure and dynamics

The hydroxyl radical and its reactivity within ice environments are crucial to many important atmospheric reactions. The associated molecular mechanisms are largely unknown due to challenges posed by direct experimental measurements and computational studies of this transient species. Here we report insights into the local structure and behaviour of the hydroxyl radical in bulk ice through an extensive study utilizing Car-Parrinello molecular dynamics simulations. Interstitial and in-lattice hydroxyl radicals in hexagonal ice were investigated at primarily 190 K. Our findings, utilizing both HCTH/120 and BLYP functionals, show that OH* can exhibit greater mobility than other ice defects (the trapping energy estimated to be only 0.09 eV). We observe the formation of a two-center three-electron hemibond structure between the hydroxyl radical and an in-lattice water molecule; while controversial, such a structure in ice may be amenable to experimental detection due to its relative stability. Our results show that interstitial water molecules can strongly influence the mobility of the hydroxyl radical in bulk ice through the displacement of the radical to an interstitial location. We also demonstrate that the H-transfer reaction from an interstitial water to the radical is a rare event in ice. Together, these results predict that the radical can be a reactive species in bulk ice, as both interstitial and in-lattice OH* can be available for reactions with other species. These microscopic insights should contribute to our understanding of the reactivity of OH* in ice and its implications to atmospheric reactions.     

Structural characterization of the picket fence (TpivPP) porphyrins Co(TpivPP), Co(TpivPP)(NO2)(1-MeIm), and Co(TpivPP)(NO2)(1,2-Me2Im)

The compounds Co(TpivPP) (1), Co(TpivPP)(NO2)(1-MeIm) (2), and Co(TpivPP)(NO2)(1,2-Me2Im) (3) have been synthesized (TpivPP = meso-tetrakis(alpha, alpha, alpha, alpha-o-pivalamidophenyl)porphyrinato dianion), and their structures have been determined with single-crystal X-ray diffraction methods. 1: a = 17.578(1) A, b = 17.596(1) A, c = 20.639(1) A, beta = 115.03(1) degrees, P2(1)/c, Z = 4, T = -120 degrees C. 2: a = 18.522(4) A, b = 18.942(4) A, c = 18.177(4) A, beta = 90.68(3) degrees, C2/c, Z = 4, T = -70 degrees C. 3: a = 18.998(4) A, b = 19.187(4) A, c = 18.000(4) A, beta = 90.96(3) degrees, C2/c, Z = 4, T = -120 degrees C. Compounds 2 and 3 have crystallographically imposed 2-fold axes. In 2 and 3, which represent R-state (relaxed) and T-state (tense) models, respectively, for hemoglobin, the NO2 ligand is bound on the "picket" side to the Co atom, and either 1-MeIm (for 2) or 1,2-Me2Im (for 3) is bound to the Co atom at the sixth coordination site on the sterically unhindered side of the molecule. The average deviations of atoms from the 24-atom porphyrin core are 0.031, 0.129, and 0.117 A for 1, 2, and 3, respectively. The Co atom is -0.043(1) A out of the mean 24-atom porphyrin plane toward the 1-MeIm ligand in 2 and -0.089(1) A out of the plane toward the 1,2-Me2Im ligand in 3. The bonds of both axial ligands in the R-state model 2, 1.898(4) A for Co-N(O2) and 1.995(4) A for Co-N(base), are shorter than the corresponding bonds in the T-state model 3, 1.917(4) A for Co-N(O2) and 2.091(4) A for Co-N(base).     

Structural,molecular, and functional insights into Schlafen proteins

Schlafen (SLFN) genes belong to a vertebrate gene family encoding proteins with high sequence homology. However, each SLFN is functionally divergent and differentially expressed in various tissues and species, showing a wide range of expression in cancer and normal cells. SLFNs are involved in various cellular and tissue-specific processes, including DNA replication, proliferation, immune and interferon responses, viral infections, and sensitivity to DNA-targeted anticancer agents. The fundamental molecular characteristics of SLFNs and their structures are beginning to be elucidated. Here, we review recent structural insights into the N-terminal, middle and C-terminal domains (N-, M-, and C-domains, respectively) of human SLFNs and discuss the current understanding of their biological roles. We review the distinct molecular activities of SLFN11, SLFN5, and SLFN12 and the relevance of SLFN11 as a predictive biomarker in oncology.Subject terms: Cancer, Cancer therapy     

Structural and mechanistic insights into C-P bond hydrolysis by phosphonoacetate hydrolase

Bacteria have evolved pathways to metabolize phosphonates as a nutrient source for phosphorus. In Sinorhizobium meliloti 1021, 2-aminoethylphosphonate is catabolized to phosphonoacetate, which is converted to acetate and inorganic phosphate by phosphonoacetate hydrolase (PhnA). Here we present detailed biochemical and structural characterization of PhnA that provides insights into the mechanism of C-P bond cleavage. The 1.35?? resolution crystal structure reveals a catalytic core similar to those of alkaline phosphatases and nucleotide pyrophosphatases but with notable differences, such as a longer metal-metal distance. Detailed structure-guided analysis of active site residues and four additional cocrystal structures with phosphonoacetate substrate, acetate, phosphonoformate inhibitor, and a covalently bound transition state mimic provide insight into active site features that may facilitate cleavage of the C-P bond. These studies expand upon the array of reactions that can be catalyzed by enzymes of the alkaline phosphatase superfamily.     

Structural studies of heparan sulfate hexasaccharides: new insights into iduronate conformational behavior

There is a growing opinion that the conformational dynamics within HS chains is critical to their observed biological activities. Investigations into HS conformational dynamics are problematic, given the structural complexity and heterogeneity of HS chains. However, this goal will be more obtainable once we understand the important roles HS sequence/sulfation patterns play in determining the conformational dynamics of iduronate units. This is the first study to compare isomers of N-sulfated oligosaccharides, with respect to the conformational versatility of their internal iduronates. Characterization by NMR spectroscopy of two HS oligosaccharides derived from porcine mucosal HS enabled the measurement of iduronate coupling constants, while under the influence of different flanking saccharide sequences. By fitting our coupling constant data to a new set of theoretical coupling constants, calculated using explicit water molecular dynamic simulations, we are able to offer new insights into the role sequence/sulfation patterns play in influencing iduronate conformational behavior. Fitting of experimental data, using our new theoretically derived coupling constants, suggests that replacement of the N-sulfate group to the reducing side of IdoUA by an N-acetyl group has little effect on the balance of IdoUA conformational equilibrium. Fitting of coupling constants for sequences GlcNS-IdoUA(2S)-GlcNS and GlcNS(6S)-IdoUA(2S)-GlcNS suggests that the flanking 6-O-sulfate group alters the balance of the IdoUA(2S) equilibrium more toward the (2)S0 conformation. There is also the suggestion that a cooperative effect may exist for N- and 6-O sulfation. These observations could be the key to understanding the important regulatory function attributed to 6-O-sulfation within HS chains.     

Ultrafast stimulated emission and structural dynamics in nickel porphyrins

The excited-state structural dynamics of nickel(II)tetrakis(2,4,6-trimethylphenyl)porphyrin (NiTMP) and nickel(II)tetrakis(tridec-7-yl)porphyrin (NiSWTP) in a toluene solution were investigated via ultrafast transient optical absorption spectroscopy. An ultrashort stimulated emission between 620 and 670 nm from the S1 state was observed in both nickel porphyrins only when this state was directly generated via Q-band excitation, whereas such a stimulated emission was absent under B (Soret)-band excitation. Because the stimulated emission in the spectral region occurs only from the S1 state, this photoexcitation-wavelength-dependent behavior of Ni(II) porphyrins is attributed to a faster intersystem crossing from the S2 state than the internal conversion S2 --> S1. The dynamics of the excited-state pathways involving the (pi, pi*) and (d, d) states varies with the meso-substituted peripheral groups, which is attributed to the nickel porphyrin macrocycle distortion from a planar configuration. Evidence for intramolecular vibrational relaxation within 2 ps and vibrational cooling in 6-20 ps of a (d, d) excited state has been established for NiTMP and NiSWTP. Finally, the lifetimes of the vibrationally relaxed (d, d) state also depend on the nature of the peripheral groups, decreasing from 200 ps for NiTMP to 100 ps for the bulkier NiSWTP.     

Axial ligand coordination in sterically strained vanadyl porphyrins: synthesis, structure, and properties

A hitherto unknown family of six-coordinate vanadyl porphyrins of the sterically crowded, nonplanar 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetranitroporphyrin incorporating axial ligand L [where L is pyridine, tetrahydrofuran (THF), or methanol (MeOH)] has been isolated as VO(tn-OEP)(L) in the solid phase for the first time and also structurally characterized. The presence of four electron-withdrawing, bulky nitro groups at the meso positions of vanadyl octaethylporphyrins severely distorts the porphyrin macrocycles and significantly enhances the affinity for the axial ligands, where even weak sigma-donating ligands, such as MeOH, bind strongly enough to be isolable in the solid phase and that too under the offset effects of the macrocyclic distortions. Thus, the axial ligand affinity is influenced by both the electronic and conformational effect, which cannot be separated completely in this series. The solid-state magnetic measurements and their typical electron paramagnetic resonance (EPR) spectrum show the presence of a single, unpaired electron, consistent with V(IV) formulation. The VO stretching frequency for VO(tn-OEP) occurs as a sharp, strong peak at 1008 cm(-1), which is consistent with five-coordinate vanadyl porphyrins, while VO(tn-OEP)(L) displays a strong band at lower wavenumbers. The downshift in nu(VO) upon axial coordination increases with increasing donor strength of the axial ligands; for pyridine, the downshift is 30 cm(-1), while for THF and MeOH, the downshifts are nearly 18 cm(-1). X-ray structure determinations authenticate axial coordination in a purely saddle-distorted porphyrin macrocycle for all of the complexes reported here in which V-Np distances are significantly shorter, while the porphyrin cores have been expanded on axial ligand coordination. As a result, vanadium atoms are more inplane than in a five-coordinate species. The binding of L does not change the spin or metal oxidation states (V(IV), d(1)-system) of the complexes; therefore, the changes observed are truly the reflections of axial ligand coordination. Electrochemical data obtained from cyclic voltammetric studies reveal that the complexes are much easier to reduce (by approximately 1200 mV) but more difficult to oxidize (by approximately 500 mV) as compared to nearly planar VO(OEP). The complexes undergo two one-electron oxidations due to pi-cation radical and dication formation and three one-electron reductions. The first two reductions are because of pi-anion radical and dianion formation, while the third quasi-reversible reduction is assigned to a metal-centered process (V(IV) --> V(III)). These results can be useful for identifying the interaction of the vanadyl porphyrins with the biological targets in their reported involvement in potent insulinomimetic activity and in anti-HIV agents.     

"Inverse-electron-demand" ligand substitution: experimental and computational insights into olefin exchange at palladium(0)

The mechanism of olefin substitution at palladium(0) has been studied, and the results provide unique insights into the fundamental reactivity of electron-rich late transition metals. A systematic series of bathocuproine-palladium(0) complexes bearing trans-beta-nitrostyrene ligands (ns(X) = X-C(6)H(4)CH=CHNO(2); X = OCH(3), CH(3), H, Br, CF(3)), (bc)Pd(0)ns(X) (3(X)), was prepared and characterized, and olefin-substitution reactions of these complexes were found to proceed by an associative mechanism. In cross-reactions between (bc)Pd(ns(CH)()3) and ns(X) (X = OCH(3), H, Br, CF(3)), more-electron-deficient olefins react more rapidly (relative rate: ns(CF)()3 > ns(Br) > ns(H) > ns(OCH)()3). Density functional theory calculations of model alkene-substitution reactions at a diimine-palladium(0) center reveal that the palladium center reacts as a nucleophile via attack of a metal-based lone pair on the empty pi orbital of the incoming olefin. This orbital picture contrasts that of traditional ligand-substitution reactions, in which the incoming ligand donates electron density into an acceptor orbital on the metal. On the basis of these results, olefin substitution at palladium(0) is classified as an "inverse-electron-demand" ligand-substitution reaction.     

Energetics and structural consequences of axial ligand coordination in nonplanar nickel porphyrins

The effects of ruffling on the axial ligation properties of a series of nickel(II) tetra(alkyl)porphyrins have been investigated with UV-visible absorption spectroscopy, resonance Raman spectroscopy, X-ray crystallography, classical molecular mechanics calculations, and normal-coordinate structural decomposition analysis. For the modestly nonplanar porphyrins, porphyrin ruffling is found to cause a decrease in binding affinity for pyrrolidine and piperidine, mainly caused by a decrease in the binding constant for addition of the first axial ligand; ligand binding is completely inhibited for the more nonplanar porphyrins. The lowered affinity, resulting from the large energies required to expand the core and flatten the porphyrin to accommodate the large high-spin nickel(II) ion, has implications for nickel porphyrin-based molecular devices and the function of heme proteins and methyl-coenzyme M reductase.     

Structural change from homogenous structure to staging in benzoic acid intercalated LDH: experimental and molecular dynamics simulation insights

The intercalation the of 4,4'-oxybis(benzoic acid) anion (OBA(2-)) into MgAl-layered double hydroxide (LDH) was carried out in formamide, and the structural change of the nanocomposites from homogenous to staging was investigated through in situ XRD, FT-IR, TG-DSC, SEM and molecular dynamics (MD) simulations. In both formamide and water, the nanocomposites had a homogenous structure with a basal spacing of ～1.7 nm, showing the configuration of OBA(2-) was vertical to the LDH layers; however, with a decrease in water content after drying, the structure changed to a staging with a basal spacing of 2.62 nm. This resulted from the 1.72 nm phase and another one of 0.85 nm, which was produced by the configuration of OBA(2-) horizontal to the LDH layers. MD simulations revealed that the LDH layers distorted surrounding OBA(2-), and the deformation became more severe with decreasing water content in the interlayer, leading to the staging formation. The simulated XRD pattern confirmed that the staging observed in the experimental pattern was of the Daumas-Hérold type.     

Metal and ligand K-edge XAS of titanium-TEMPO complexes: determination of oxidation states and insights into Ti-O bond homolysis

Ti-TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) provides a means for generating Ti(III) complexes by homolysis of the Ti-O bond. It has been determined that bis-Cp-Ti-TEMPO complexes readily undergo homolytic cleavage while the mono-Cp-Ti-TEMPO complexes do not. Here Ti K- and Cl K-edge XAS are applied to directly determine the oxidation state of TiCl3TEMPO, TiCpCl2TEMPO, and TiCp2ClTEMPO, with reference to Ti(III) and Ti(IV) complexes of known oxidation state. The Ti K-edge data show that Ti(III) complexes exhibit a pre-edge feature approximately 1 eV lower than any of the Ti(IV) complexes; while the Cl K-edges show that Ti(III) complexes have a Cl K- pre-edge feature to approximately 1 eV higher energy than any of the Ti(IV) complexes. Taken together, the Ti and Cl K-edge data indicate that the Ti-TEMPO complexes are best described as Ti(IV)-TEMPO anions (rather than Ti(III)-nitroxyl radicals). In addition, the Cl K-edges indicate that replacement of Cl by Cp weakens the bonding with the remaining ligands, with the Cl 3p covalency decreasing from 25% to 21% to 17% on going from TiCl3TEMPO to TiCpCl2TEMPO to TiCp2ClTEMPO. DFT calculations also show that the electronic structures of the Ti-TEMPO complexes are modulated by the replacement of chloride by Cp. The effect of the Cp on the ancillary ligation is one factor that contributes to facile Ti-O bond homolysis in TiCp2ClTEMPO. However, the results indicate the primary contribution to the energetics of Ti-O bond homolysis in TiCp2ClTEMPO is stabilization of the three-coordinate product by Cp.     

Anisochronous dynamics in a crystalline array of steroidal molecular rotors: evidence of correlated motion within 1D helical domains

We describe the solid-state dynamics of a molecular rotator (2) consisting of a p-phenylene rotor flanked by two ethynyl steroidal moieties that act as a stator. Single-crystal X-ray diffraction analysis of polymorph I revealed a packing motif containing 1D columns of nested rotors arranged in helical arrays (space group P3(2)) with the central phenylenes disordered over two sites related by an 85° rotation about their 1,4-axes. Unexpected line shapes in quadrupolar-echo (2)H NMR measurements between 155 and 296 K for the same polymorph with a deuterated phenylene isotopologue (2-d(4)) were simulated by trajectories involving fast (>10(8) s(-1)) 180° rotation (twofold flips) in each of the two rotationally disordered sites and slower exchange (2 × 10(4) to 1.5 × 10(6) s(-1)) between them. A negative activation entropy and a low enthalpic barrier for the slower 85° exchange are interpreted in terms of highly correlated processes within the 1D helical domains.     

Swallowtail porphyrins: synthesis, characterization and incorporation into porphyrin dyads

The incorporation of symmetrically branched tridecyl ("swallowtail") substituents at the meso positions of porphyrins results in highly soluble building blocks. Synthetic routes have been investigated to obtain porphyrin building blocks bearing 1-4 swallowtail groups. Porphyrin dyads have been synthesized in which the zinc or free base (Fb) porphyrins are joined by a 4,4'-diphenylethyne linker and bear swallowtail (or n-pentyl) groups at the nonlinking meso positions. The swallowtail-substituted Zn(2)- and ZnFb-dyads are readily soluble in common organic solvents. Static absorption and fluorescence spectra and electrochemical data show that the presence of the swallowtail groups slightly raises the energy level of the filled a(2u)(pi) HOMO. EPR studies of the pi-cation radicals of the swallowtail porphyrins indicate that the torsional angle between the proton on the alkyl carbon and p-orbital on the meso carbon of the porphyrin is different from that of a porphyrin bearing linear pentyl groups. Regardless, the swallowtail substituents do not significantly affect the photophysical properties of the porphyrins or the electronic interactions between the porphyrins in the dyads. In particular, time-resolved spectroscopic studies indicate that facile excited-state energy transfer occurs in the ZnFb dyad, and EPR studies of the monocation radical of the Zn(2)-dyad show that interporphyrin ground-state hole transfer is rapid.     

Structural and molecular characterization of meso-substituted zinc porphyrins: a DFT supported study

Structural parameters of a range of over 100 meso-substituted zinc porphyrins were reviewed and compared to show how far the nature of the functional group may affect the interatomic distances and bond angles within the porphyrin core. It was proved that even despite evident deformations of the molecular structure, involving twisting of the porphyrin's central plane, the coupled π-bonding system remains flexible and stable. DFT calculations were applied to a number of selected porphyrins representative for the reviewed compounds to emphasize the relevance of theoretical methods in structural investigations of complex macrocyclic molecular systems. Experimental and DFT-simulated IR spectral data were reported and analyzed in context of the individual molecular features introduced by the meso substituents into the porphyrin moiety base. Raw experimental spectral data, including 1H- and 13C-NMR, UV-Vis, FTIR, XRD, and other relevant physicochemical details have been provided for a specially chosen reference zinc porphyrin functionalized by tert-butylphenyl groups.     

Synthesis of urea picket porphyrins and their use in the elucidation of the role buried solvent plays in the selectivity and stoichiometry of anion binding receptors

The synthesis of alpha,alpha-5,10-diurea and alpha,alpha,alpha-5,10,15-triurea picket porphyrins are detailed in this report. In previous reports, these porphyrins, along with alpha,alpha,alpha,alpha-5,10,15,20-tetraurea picket porphyrin, were used to demonstrate the important role one buried solvent molecule plays in the selectivity and stoichiometry of binding inorganic anions. Building on prior work, this report discusses the results of acetate anion binding studies between tetra- and diurea picket porphyrins (the latter does not contain a buried solvent molecule in the anion-receptor complex), compares differences in thermodynamic data obtained from van't Hoff plots of a porphyrin anion receptor able to utilize buried solvent in its binding motif with one that does not, and compares the crystal structure of a tetraurea porphyrin 1-chloride anion complex that contains buried solvent with new X-ray crystal structures of tetraurea porphyrin 1-dichloride or bisdihydrogenphosphate anion complexes that contain no buried solvent. Data from our previous work, and the work described herein, demonstrates that one buried solvent molecule provides stability to the receptor-anion complex that is similar in energy to a moderately strong hydrogen bond.