Perspectives on the reaction force constant

A synchronous, concerted chemical process is rigorously divided by the reaction force F(R), the negative gradient of V(R), into “reactant” and “product” regions which are dominated by structural changes and an intervening “transition” region which is electronically intensive. The reaction force constant κ(R), the second derivative of V(R), is negative throughout the transition region, not just at the nominal transition state, at which κ(R) has a minimum. This is consistent with experimental evidence that there is a transition region, not simply a specific point. We show graphically that significant nonsynchronicity in the process is associated with the development of a maximum of κ(R) in the transition region, which increases as the process becomes more nonsynchronous. (We speculate that for a nonconcerted process this maximum is actually positive.) Thus, κ(R) can serve as an indicator of the level of nonsynchronicity.

Fine structure in the transition region: reaction force analyses of water-assisted proton transfers

We have analyzed the variation of the reaction force F(ξ) and the reaction force constant κ(ξ) along the intrinsic reaction coordinates ξ of the water-assisted proton transfer reactions of HX-N = Y (X,Y = O,S). The profile of the force constant of the vibration associated with the reactive mode, k _ξ (ξ), was also determined. We compare our results to the corresponding intramolecular proton transfers in the absence of a water molecule. The presence of water promotes the proton transfers, decreasing the energy barriers by about 12 – 15 kcal mol^-1. This is due in part to much smaller bond angle changes being needed than when water is absent. The κ(ξ) profiles along the intrinsic reaction coordinates for the water-assisted processes show striking and intriguing differences in the transition regions. For the HS-N = S and HO-N = S systems, two κ(ξ) minima are obtained, whereas for HO-N = O only one minimum is found. The k _ξ (ξ) show similar behavior in the transition regions. We propose that this fine structure reflects the degree of synchronicity of the two proton migrations in each case.

Variation of the electronic dipole polarizability on the reaction path

The reaction force and the electronic flux, first proposed by Toro-Labbé et al. (J Phys Chem A 103:4398, 1999) have been expressed by the existing conceptual DFT apparatus. The critical points (extremes) of the chemical potential, global hardness and softness have been identified by means of the existing and computable energy derivatives: the Hellman-Feynman force, nuclear reactivity and nuclear stiffness. Specific role of atoms at the reaction center has been unveiled by indicating an alternative method of calculation of the reaction force and the reaction electronic flux. The electron dipole polarizability on the IRC has been analyzed for the model reaction HF + CO→HCOF. The electron polarizability determined on the IRC α _e (ξ) was found to be reasonably parallel to the global softness curve S(ξ). The softest state on the IRC (not TS) coincides with zero electronic flux.

A major QTL associated with Fusarium oxysporum race 1 resistance identified in genetic populations derived from closely related watermelon lines using selective genotyping and genotyping-by-sequencing for SNP discovery

Key message

A major quantitative trait locus (QTL) for Fusarium oxysporum Fr. f. sp. niveum race 1 resistance was identified by employing a “selective genotyping” approach together with genotyping-by-sequencing technology to identify QTLs and single nucleotide polymorphisms associated with the resistance among closely related watermelon genotypes.

Abstract

Fusarium wilt is a major disease of watermelon caused by the soil-borne fungus Fusarium oxysporum Schlechtend.:Fr. f. sp. niveum (E.F. Sm.) W.C. Snyder & H.N. Hans (Fon). In this study, a genetic population of 168 F₃ families (24 plants in each family) exhibited continuous distribution for Fon race 1 response. Using a “selective genotyping” approach, DNA was isolated from 91 F₂ plants whose F₃ progeny exhibited the highest resistance (30 F₂ plants) versus highest susceptibility (32 F₂ plants), or moderate resistance to Fon race 1 (29 F₂ plants). Genotyping-by-sequencing (GBS) technology was used on these 91 selected F₂ samples to produce 266 single nucleotide polymorphism (SNP) markers, representing the 11 chromosomes of watermelon. A major quantitative trait locus (QTL) associated with resistance to Fon race 1 was identified with a peak logarithm of odds (LOD) of 33.31 and 1-LOD confidence interval from 2.3 to 8.4 cM on chromosome 1 of the watermelon genetic map. This QTL was designated “Fo-1.1” and is positioned in a genomic region where several putative pathogenesis-related or putative disease-resistant gene sequences were identified. Additional independent, but minor QTLs were identified on chromosome 1 (LOD 4.16), chromosome 3 (LOD 4.36), chromosome 4 (LOD 4.52), chromosome 9 (LOD 6.8), and chromosome 10 (LOD 5.03 and 4.26). Following the identification of a major QTL for resistance using the “selective genotyping” approach, all 168 plants of the F ₂ population were genotyped using the SNP nearest the peak LOD, confirming the association of this SNP marker with Fon race 1 resistance. The results in this study should be useful for further elucidating the mechanism of resistance to Fusarium wilt and in the development of molecular markers for use in breeding programs of watermelon.     

Computational investigations on the electronic and structural properties of the unsaturated silylenoid HP=SiLiF

The structures of unsaturated silylenoid HP=SiLiF were studied by density functional theory at the B3LYP/6-311+G(d,P) level. Four equilibrium structures, the three-membered ring (1), the four-membered ring (2), the “classical” silane (3), and the linear (4) structures, were located. Their energies are in the order of 4?>?3?>?1?>?2. To exploit the stability of HP=SiLiF, the insertions reaction of 2 and HP=Si into C-Cl have been investigated, respectively. The results show that the insertion of HP=Si is more favorable. To compare with the saturated silylenoid, the insertion reaction of H₂SiLiF was also investigated. The calculations indicate that the insertion of HP=SiLiF (2) is more favorable. The unsaturated siylenoid HP=SiLiF has similar reaction characters to saturated silylenoid H₂SiLiF and silylene HP=Si.     

Relating normal vibrational modes to local vibrational modes: benzene and naphthalene

Local vibrational modes can be directly derived from normal vibrational modes using the method of Konkoli and Cremer (Int J Quant Chem 67:29, 1998). This implies the calculation of the harmonic force constant matrix F ^q (expressed in internal coordinates q) from the corresponding Cartesian force constant matrix f ^x with the help of the transformation matrix U?=?WB ^?(BWB ^?)^?1 (B: Wilson’s B-matrix). It is proven that the local vibrational modes are independent of the choice of the matrix W. However, the choice W?=?M ^?1 (M: mass matrix) has numerical advantages with regard to the choice W?=?I (I: identity matrix), where the latter is frequently used in spectroscopy. The local vibrational modes can be related to the normal vibrational modes in the form of an adiabatic connection scheme (ACS) after rewriting the Wilson equation with the help of the compliance matrix. The ACSs of benzene and naphthalene based on experimental vibrational frequencies are discussed as nontrivial examples. It is demonstrated that the local-mode stretching force constants provide a quantitative measure for the C–H and C–C bond strength.     

Characterization of bio-related vanadium and zinc complexes containing tetradentate dithiolate-disulfide, -diamine and -amine-amide ligands

The reaction of [VCl₃(PMe₂Ph)₃] _{with HSS′S′SH (where the HS are thiophenolate and the S′ thioether functions, respectively), H2–1, yields [VCl(μ-SS′S′S)]2 (3) with one of the thiolate groups of each of the two ligands in the bridging mode. Reaction of Na2–1 with [VOCl2(thf)2] leads to a polymeric product of composition [VO(SS′S′S)]x (4). The products obtained from the reaction between [VOCl2(thf)2] and NaSNNSNa, Na2–2, (S is thiophenolate, N the amine function) depend on subtle changes in the diamine backbone of this ligand: If the amine functions are linked by -CH2CH2– (2a), the tetranuclear V^IV complex [V(SNNS)μ-O]4 (5) is formed alongside the V^III complex [VCl(SNNS)]. If the backbone is -CH(Me)CH(Me)- (2b), [VO(SNNS)] (7) and the dinuclear, asymmetrically oxo-bridged V^IV complex [{(SNN ^– S)(thf)V}μ-O{V(SNN ^– S)}] (8) are obtained. In 8, one amine of each of the two ligands is deprotonated to the amide group. In either case, the complexation is accompanied by oxidation of the thiolates to disulfides, leading to the generation of teraazatetrathio-cycloeicosanes (6a/b). Compounds 5 and 8·2THF have been structurally characterized by X-ray analyses. The connectivities have further been established for 3·2CH2Cl2 and for 6b, which exhibits the same conformation as formally characterized 6a. The cluster compound 5 is stabilized by an extended intramolecular N-H...O and N-H...S) hydrogen-bonding network. In 7·2THF, one of the THFs of crystallization is hydrogen-bonded to the NH of the penta-coordinated {VO(SNN ^– S)} moiety; further, there is an intramolecular hydrogen bond between one of the thiolates of this tetragonal-pyramidal half of the molecule and the NH of the octahedral {VO(SNN ^– S)thf} half. The generation of the ligand 2b from its precursor compound, the zinc complex [Zn(SNNS)] (9) leads to the structural characterization of 9·CH3OH with a large SZnS bite angle and a strong hydrogen bond between the methanolic OH and one of the thiolate sulfurs. The relevance of these compounds in biological systems is discussed.}     

Hyperfine interactions and electron distribution in FeIIFeI and FeIFeI models for the active site of the [FeFe] hydrogenases: Mössbauer spectroscopy studies of low-spin FeI

Mössbauer studies of [{μ-S(CH₂C(CH₃)₂CH₂S}(μ-CO)Fe^IIFe^I(PMe₃)₂(CO)₃]PF₆ (1 _OX ), a model complex for the oxidized state of the [FeFe] hydrogenases, and the parent Fe^IFe^I derivative are reported. The paramagnetic 1 _OX is part of a series featuring a dimethylpropanedithiolate bridge, introducing steric hindrance with profound impact on the electronic structure of the diiron complex. Well-resolved spectra of 1 _OX allow determination of the magnetic hyperfine couplings for the low-spin distal Fe^I ( $ {\text{Fe}}^{\text{I}} _{\text{ D}} $ Fe D I ) site, A _x,y,z  = [?24 (6), ?12 (2), 20 (2)] MHz, and the detection of significant internal fields (approximately 2.3 T) at the low-spin ferrous site, confirmed by density functional theory (DFT) calculations. Mössbauer spectra of 1 _OX show nonequivalent sites and no evidence of delocalization up to 200 K. Insight from the experimental hyperfine tensors of the Fe^I site is used in correlation with DFT to reveal the spatial distribution of metal orbitals. The Fe–Fe bond in [Fe₂{μ-S(CH₂C(CH₃)₂CH₂S}(PMe₃)₂(CO)₄] (1) involving two $ d_{{z^{2} }} $ d z 2 -type orbitals is crucial in keeping the structure intact in the presence of strain. On oxidation, the distal iron site is not restricted by the Fe–Fe bond, and thus the more stable isomer results from inversion of the square pyramid, rotating the $ d_{{z^{2} }} $ d z 2 orbital of $ {\text{Fe}}^{\text{I}} _{\text{ D}} $ Fe D I . DFT calculations imply that the Mössbauer properties can be traced to this $ d_{{z^{2} }} $ d z 2 orbital. The structure of the magnetic hyperfine coupling tensor, A, of the low-spin Fe^I in 1 _OX is discussed in the context of the known A tensors for the oxidized states of the [FeFe] hydrogenases.     

Synthesis of [SnPh2(SR)2] SR = SC6F4-4-H, SC6F5: Reactivity towards group 10 transition metal complexes

The organometallic tin(IV) complexes [SnPh₂(SR^F)₂] SR^F = ⁻SC₆F₄-4-H (1), ⁻SC₆F₅ (2), were synthesized and their reactivity with [MCl₂(PPh₃)₂] M = Ni, Pd and Pt explored. Thus, transmetallation products were obtained affording polymeric [Ni(SR^F)(μ-SR^F)]_n, monomeric cis-[Pt(PPh₃)₂(SC₆F₄-4-H)₂] (3) and cis-[Pt(PPh₃)₂(SC₆F₅)₂] (4) and dimeric species [Pd(PPh₃)(SC₆F₄-4-H)(μ-SC₆F₄-4-H)]₂ (5) and [Pd(PPh₃)(SC₆F₅)(μ-SC₆F₅)]₂ (6) for Ni, Pt and Pd, respectively. The crystal structures of complexes 1, 2, 3, 4 and 6 were determined.     

Changes of phytoplankton functional groups in a floodplain lake associated with hydrological perturbations

During the past decade, basic hydrological conditions of a floodplain lake in the middle Danube section have been altered with long-lasting extremely high flooding. The objective of the paper is to show the effectiveness of the functional approach to explain phytoplankton changes associated with hydrological events. Intensity and duration of flooding were qualified as the primary cause for the changes of functional groups. Flooding phase was characterised by diatoms (B, C, D, P, T _B ) tolerant to water column mixing. Due to the dilution and washout effect their biomass was low during the long-lasting flooding despite their input from the river. Co-occurrence of coccoid green algae (X1, J, F) was associated with turbid and mixed waters. High-nutrient concentrations and water column stability during the long-term dry conditions led to the dominance and high biomass of cyanobacteria. Low-nitrogen H1 group was particularly sensitive to stress caused by flooding, while filamentous N₂-fixing (S _N ) and non N₂-fixing species (S1) showed tolerance to short-term flooding. The development of euglenoids and dinoflagellates (W1, W2, L _O ) was also associated with dry conditions and seasonal changes in autumn. The functional classification allows representing of the hydrological phases which characterise the phytoplankton succession in highly disturbed river-floodplain systems.     

Ruthenium hydride-catalyzed regioselective addition of benzaldehyde to dienes leading to β,γ-unsaturated ketones: a DFT study

Density functional theory (DFT) was used to investigate the ruthenium hydride-catalyzed regioselective addition reactions of benzaldehyde to isoprene leading to the branched β,γ-unsaturated ketone. All intermediates and the transition states were optimized completely at the B3LYP/6-31?G(d,p) level (LANL2DZ(f) for Ru, LANL2DZ(d) for P and Cl). Calculated results indicated that three catalysts RuHCl(CO)(PMe₃)₃ (1), RuH₂(CO)(PMe₃)₃ (2), and RuHCl(PMe₃)₃ (3) exhibited different catalysis, and the first was the most excellent. The most favorable reaction pathway included the coordination of 1 to the less substituted olefin of isoprene, a hydrogen transfer reaction from ruthenium to the carbon atom C1, the complexation of benzaldehyde to ruthenium, the carbonyl addition, and the hydride elimination reaction. The carbonyl addition was the rate-determining step. The dominant product was the branched β,γ-unsaturated ketone. Furthermore, the presence of one toluene molecule lowered the activation free energy of the transition state of the carbonyl addition by hydrogen bonds between the protons of toluene and the chlorine, carbonyl oxygen of the ruthenium complex. On the whole, the solvent effect decreased the free energies of the species.

Theoretical description of halogen bonding – an insight based on the natural orbitals for chemical valence combined with the extended-transition-state method (ETS-NOCV)

In the present study we have characterized the halogen bonding in selected molecules H₃N–ICF₃ (1-NH ₃ ), (PH₃)₂C–ICF₃ (1-CPH ₃ ), C₃H₇Br–(IN₂H₂C₃)₂C₆H₄ (2-Br), H₂–(IN₂H₂C₃)₂C₆H₄ (2-H ₂ ) and Cl–(IC₆F₅)₂C₇H₁₀N₂O₅ (3-Cl), containing from one halogen bond (1-NH ₃ , 1-CPH ₃ ) up to four connections in 3-Cl (the two Cl–HN and two Cl–I), based on recently proposed ETS-NOCV analysis. It was found based on the NOCV-deformation density components that the halogen bonding C–X ^… B (X-halogen atom, B-Lewis base), contains a large degree of covalent contribution (the charge transfer to X ^… B inter-atomic region) supported further by the electron donation from base atom B to the empty σ*(C–X) orbital. Such charge transfers can be of similar importance compared to the electrostatic stabilization. Further, the covalent part of halogen bonding is due to the presence of σ-hole at outer part of halogen atom (X). ETS-NOCV approach allowed to visualize formation of the σ-hole at iodine atom of CF₃I molecule. It has also been demonstrated that strongly electrophilic halogen bond donor, [C₆H₄(C₃H₂N₂I)₂][OTf]₂, can activate chemically inert isopropyl bromide (2-Br) moiety via formation of Br–I bonding and bind the hydrogen molecule (2-H ₂ ). Finally, ETS-NOCV analysis performed for 3-Cl leads to the conclusion that, in terms of the orbital-interaction component, the strength of halogen (Cl–I) bond is roughly three times more important than the hydrogen bonding (Cl–HN).

Spin-flip reactions of Zr + C2H6 researched by relativistic density functional theory

Density functional theory (DFT) with relativistic corrections of zero-order regular approximation (ZORA) has been applied to explore the reaction mechanisms of ethane dehydrogenation by Zr atom with triplet and singlet spin-states. Among the complicated minimum energy reaction path, the available states involves three transition states (TS), and four stationary states (1) to (4) and one intersystem crossing with spin-flip (marked by ?): ³ Zr + C ₂ H ₆ → ³ Zr-CH ₃ -CH ₃ ( ³ 1) → ³ TS _1/2 → ³ ZrH-CH ₂ -CH ₃ ( ³ 2) → ³ TS _2/3 ? ¹ ZrH₂-CH₂ = CH₂ ( ¹ 3) → ¹ TS _3/4 → ¹ ZrH ₃ -CH = CH ₂ ( ¹ 4). The minimum energy crossing point is determined with the help of the DFT fractional-occupation-number (FON) approach. The spin inversion leads the reaction pathway transferring from the triplet potential energy surface (PES) to the singlet’s accompanying with the activation of the second C-H bond. The overall reaction is calculated to be exothermic by about 231 kJ mol^?1. Frequency and NBO analysis are also applied to confirm with the experimental observed data.

Ruthenium (II) polypyridyl complexes stabilize the bcl-2 promoter quadruplex and induce apoptosis of Hela tumor cells

In the present study, the interaction between GC-rich sequence of bcl-2 gene P1 promoter (Pu39) and two ruthenium (II) polypyridyl complexes, [Ru(bpy)₂(tip)]²⁺ (1) and [Ru(phen)₂(tip)]²⁺ (2), was investigated by UV–Visible, fluorescence spectroscopy, circular dichroism, fluorescence resonance energy transfer melting assay and polymerase chain reaction stop assay. Those experimental results indicated that the two complexes can effectively stabilize the G-quadruplex of Pu39. It was found that the complex 2 exhibited greater cytotoxic activity than 1 against human Hela cells and can enter into Hela cells in a short period of time to effectively induce apoptosis of cells. Further experiments found that complexes 1 and 2 had as potent inhibitory effects on ECV-304 cell migration as suramin. Those noteworthy results provide new insights into the development of anticancer agents for targeting G-quadruplex DNA.     

Novel halogen-bridged bisphosphine nickel(II) complexes

Reaction of [NiCl₂(dtbpe)] (dtbpe = 1,2-bis(di-tert-butylphosphino)ethane) with one equivalent of NaBAr^F₄ (BAr^F₄ = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) gives the dinuclear chloro-bridged nickel complex [Ni₂(μ-Cl)₂(dtbpe)₂](BAr^F₄)₂ (1). [Ni(solv)₆](BF₄)₂ reacts with dtbpe to give, depending on the solvent, the fluoro-bridged complex [Ni₂(μ-F)₂(dtbpe)₂](BF₄)₂ (2) (solv = THF) or the mononuclear chelate complex [Ni(MeCN)₂(dtbpe)](BF₄)₂ (3) (solv = MeCN). In 1-3, nickel cations are coordinated in a square-planar fashion according to X-ray crystallography. No Ni-Ni interaction was observed in dinuclear halogen-bridged complexes 1 and 2.     

Metal–drug synergy: new ruthenium(II) complexes of ketoconazole are highly active against Leishmania major and Trypanosoma cruzi and nontoxic to human or murine normal cells

In our ongoing search for new metal-based chemotherapeutic agents against leishmaniasis and Chagas disease, six new ruthenium–ketoconazole (KTZ) complexes have been synthesized and characterized, including two octahedral coordination complexes—cis,fac-[Ru^IICl₂(DMSO)₃(KTZ)] (1) and cis-[Ru^IICl₂(bipy)(DMSO)(KTZ)] (2) (where DMSO is dimethyl sulfoxide and bipy is 2,2′-bipyridine)—and four organometallic compounds—[Ru^II(η⁶-p-cymene)Cl₂(KTZ)] (3), [Ru^II(η⁶-p-cymene)(en)(KTZ)][BF₄]₂ (4), [Ru^II(η⁶-p-cymene)(bipy)(KTZ)][BF₄]₂ (5), and [Ru^II(η⁶-p-cymene)(acac)(KTZ)][BF₄] (6) (where en is ethylenediamine and acac is acetylacetonate); the crystal structure of 3 is described. The central hypothesis of our work is that combining a bioactive compound such as KTZ and a metal in a single molecule results in a synergy that can translate into improved activity and/or selectivity against parasites. In agreement with this hypothesis, complexation of KTZ with Ru^II in compounds 3–5 produces a marked enhancement of the activity toward promastigotes and intracellular amastigotes of Leishmania major, when compared with uncomplexed KTZ, or with similar ruthenium compounds not containing KTZ. Importantly, the selective toxicity of compounds 3–5 toward the leishmania parasites, in relation to human fibroblasts and osteoblasts or murine macrophages, is also superior to the selective toxicities of the individual constituents of the drug. When tested against Trypanosoma cruzi epimastigotes, some of the organometallic complexes displayed activity and selectivity comparable to those of free KTZ. A dual-target mechanism is suggested to account for the antiparasitic properties of these complexes.     

Mononuclear and dinuclear model hydrolases of nickel and cobalt

Reaction between the dinuclear model hydrolases [M₂(μ-OAc)₂(OAc)₂(μ-H₂O)(tmen)₂]; M = Ni (1); M = Co (2) and trimethylsilyltrifluoromethanesulphonate (TMS-OTf) under identical reaction conditions gives the mononuclear complex [Ni(OAc)(H₂O)₂(tmen)][OTf] · H₂O (3) in the case of nickel and the dinuclear complex [Co₂(μ-OAc)₂(μ-H₂O)₂(tmen)₂][OTf]₂ (4) in the case of cobalt.Reaction of (3) with urea gives the previously reported [Ni(OAc)(urea)₂(tmen)][OTf] (5), whereas (4) gives [Co₂(OAc)₃(urea)(tmen)₂][OTf] (6) previously obtained by direct reaction of (2) with urea. Both (3) and (4) react with monohydroxamic acids (RHA) to give the dihydroxamate bridged dinuclear complexes [M₂(μ-OAc)(μ-RA)₂(tmen)₂][OTf]; M = Ni (7); M = Co (8) previously obtained by the reaction of (1) and (2) with RHA, illustrating the greater ability of hydroxamic acids to stabilize dinuclear complexes over that of urea by means of their bridging mode, and offering a possible explanation for the inhibiting effect of hydroxamic acids by means of their displacing bridging urea in a possible intermediate invoked in the action of urease.     

Synthesis of some quinolinyl chalcone analogues and investigation of their anticancer and synergistic anticancer effect with doxorubicin

Two derivatives of 2-(4-acetylanilino)quinolines (IIIa, b) were synthesized as scaffolds for synthesis of open chalcone analogues (Va-f) through Claisen-Schmidt condensation with a set of aromatic aldehydes (IVa-d). Derivatives (Va, b) were further manipulated into cyclic ??,??-unsaturated ketones by Michael-addition of acetylacetone and ethylacetoacetate affording derivatives (VI?CVII). Deethoxycarboxylation of derivatives (VIIa, b) afforded cyclohexenons (VIIIa, b) allowing formation of a mini library of ??,??-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open enones, (Vb) and (Ve), showed significant anticancer activity with IC₅₀ of 5.0 and 2.5 ??M respectively. Only one cyclic enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 ??M.