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.

Dimeric bisbenzimidazoles: Cytotoxicity and effects on DNA methylation in normal and cancer human cells

Cancer cells are characterized by hypermethylation of the promoter regions of tumor suppressor genes. DNA methyltransferase inhibitors reactivate the genes, pointing to DNA methyltransferases as potential targets for anticancer therapy. Dimeric bisbenzimidazoles varying in the length of an oligomeric linker between two bisbenzimidazole residues (DB(n), where n is the number of methylene groups in the linker) were earlier shown to efficiently inhibit methylation of DNA duplexes by murine DNA methyltransferase Dnmt3a. Here, some of the compounds were tested for cytotoxicity, cell penetration, and effect on genomic DNA methylation in F-977 fetal lung fibroblasts and HeLa cervical cancer cells. Within the 0–60 μM concentration range, only DB(11) exerted a significant toxic effect on normal cells, whereas the effects of DB(n) on cancer cells were not significant. DB(1) and DB(3) slightly stimulated proliferation of HeLa and F-977 cells, respectively. DB(1) and DB(3) penetrated into the nuclei of HeLa and F-977 cells and accumulated predominantly in or near the nucleolus, while DB(11) was incapable of nuclear penetration. HeLa cells incubated with 26 μM DB(1) or DB(3) displayed a decrease in methylation of the 18S rRNA gene, which was in the regions of predominant accumulation of DB(1) and DB(3). The same DB(3) concentration exerted a similar effect on F-977 cells. However, the overall genomic DNA methylation level remained unchanged in both of the cell lines. The results indicated that DB(n)-type compounds can be used to demethylate certain genes and are thereby promising as potential anticancer agents.     

Trypanocidal and cytotoxic evaluation of synthesized thiosemicarbazones as potential drug leads against sleeping sickness

Thiosemicarbazones have become one of the promising compounds as new clinical candidates due to their wide spectrum of pharmaceutical activities. The wide range of their biological activities depends generally on their related aldehyde or ketone groups. Here, we report the pharmacological activities of some thiosemicarbazones synthesized in this work. Benzophenone and derivatives were used with N(4)-phenyl-3-thiosemicarbazide to synthesize corresponding five thiosemicarbazones (1–5). Their structures were characterized by spectrometrical methods analysis IR, NMR ¹H & ¹³C and MS. The compounds were then screened in vitro for their antiparasitic activity and toxicity on Trypanosoma brucei brucei and Artemia salina Leach respectively. The selectivity index of each compound was also determined. Four thiosemicarbazones such as 4, 2, 3 and 1 reveal interesting trypanocidal activities with their half inhibitory concentration (IC₅₀) equal to 2.76, 2.83, 3.86 and 8.48 μM respectively, while compound 5 (IC₅₀ = 12.16 μM) showed a moderate anti-trypanosomal activity on parasite. In toxicity test, except compound 1, which showed a half lethal concentration LC₅₀ >281 μM, the others exerted toxic effect on larvae with LC₅₀ of 5.56, 13.62, 14.55 and 42.50 μM respectively for thiosemicarbazones 4, 5, 3 and 2. In agreement to their selectivity index, which is greater than 1 (SI >1), these compounds clearly displayed significant selective pharmaceutical activities on the parasite tested. The thiosemicarbazones 2–5 that displayed significant anti-trypanosomal and cytoxicity activities are suggested to have anti-neoplastic and anti-cancer activities.     

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.     

Driving and retarding forces in a chemical reaction

The reaction force F(ξ) is the negative gradient of the potential energy of a chemical process along the intrinsic reaction coordinate ξ. We extend the rigorous concept of F(ξ) to the “activation strain model” of Bickelhaupt et al., to formulate the “strain” force F _str(ξ) that retards a reaction and the “interaction” force F _int(ξ) that drives it. These are investigated for a group of Diels-Alder cycloadditions. The results fully support the interpretation of the minimum of F(ξ) as defining the beginning of the transition from deformed reactants to eventual products.     

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.}     

Different non-host resistance responses of two rice subspecies,japonica and indica,to Puccinia striiformis f. sp. tritici

Key message

Japonica and indica have different non-host resistance (NHR) abilities to Puccinia striiformis f. sp. tritici ( Pst ), and hydrogen peroxide (H ₂ O ₂ ) has a positive function in NHR to japonica against Pst.

Abstract

Non-host interactions between Puccinia striiformis f. sp. tritici (Pst) and two rice subspecies were characterized using 23 rice varieties, including 11 japonica and 12 indica. Results showed that the infected fungal structures were easily produced in the leaves of indica, whereas only several substomatal vesicles and primary infection hyphae were observed in the leaves of japonica. This result indicated that indica is less resistant or more susceptible to Pst than japonica. Hydrogen peroxide accumulated in the initial phase of japonica–Pst interaction but not in indica–Pst interaction. A set of reactive oxygen species (ROS)-related genes was also induced in response to Pst infection, suggesting that ROS activation is one of the major mechanisms of non-host resistance of rice to Pst.     

Di- and polynuclear silver(I) saccharinate complexes of tertiary diphosphane ligands: synthesis, structures, in vitro DNA binding, and antibacterial and anticancer properties

A series of new silver(I) saccharinate (sac) complexes, [Ag₂(sac)₂(μ-dppm)H₂O]·H₂O (1), {[Ag₂(μ-sac)₂(μ-dppe)]·3H₂O·CH₂Cl₂} _n (2), [Ag₂(μ-sac)₂(μ-dppp)] _n (3), and [Ag(sac)(μ-dppb)] _n (4) [dppm is 1,1-bis(diphenylphosphino)methane, dppe is 1,2-bis(diphenylphosphino)ethane, dppp is 1,3-bis(diphenylphosphino)propane, and dppb is 1,4-bis(diphenylphosphino)butane], have been synthesized and characterized by C, H, N elemental analysis, IR spectroscopy, ¹H NMR, ¹³C NMR, and ³¹P NMR spectroscopy, electrospray ionization mass spectrometry, and thermogravimetry–differential thermal analysis. Single-crystal X-ray studies show that the diphosphanes act as bridging ligands to yield a dinuclear complex (1) and one-dimensional coordination polymers (2 and 4), whereas the sac ligand adopts a μ₂-N/O bridging mode in 2, and is N-coordinated in 1 and 4. The interaction of the silver(I) complexes with fish sperm DNA was investigated using UV–vis spectroscopy, fluorescence spectroscopy, and agarose gel electrophoresis. The binding studies indicate that the silver(I) complexes can interact with fish sperm DNA through intercalation, and complexes 1 and 3 have the highest binding affinity. The gel electrophoresis assay further confirms the binding of the complexes with the pBR322 plasmid DNA. The minimum inhibitory concentrations of the complexes indicate that complex 1 exhibits very high antibacterial activity against standard bacterial strains of Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus, being much higher than those of AgNO₃, silver sulfadiazine, ciprofloxacin, and gentamicin. Moreover, complexes 1–3 exhibit very high cytotoxic activity against A549 and MCF-7 cancer cell lines, compared with AgNO₃ and cisplatin. The bacterial and cell growth inhibitions of the silver(I) complexes are closely related to their DNA binding affinities.     

N(4)-Tolyl-2-acetylpyridine thiosemicarbazones and their platinum(II,IV) and gold(III) complexes: cytotoxicity against human glioma cells and studies on the mode of action

Complexes [Au(2Ac4oT)Cl][AuCl₂] (1), [Au(H_py2Ac4mT)Cl₂]Cl·H₂O (2), [Au(H_py2Ac4pT)Cl₂]Cl (3), [Pt(H2Ac4oT)Cl]Cl (4), [Pt(2Ac4mT)Cl]·H₂O (5), [Pt(2Ac4pT)Cl] (6) and [Pt(L)Cl₂OH], L = 2Ac4mT (7), 2Ac4oT (8), 2Ac4pT (9) were prepared with N(4)-ortho- (H2Ac4oT), N(4)-meta- (H2Ac4mT) and N(4)-para- (H2Ac4pT) tolyl-2-acetylpyridine thiosemicarbazone. The cytotoxic activities of all compounds were assayed against U-87 and T-98 human malignant glioma cell lines. Upon coordination cytotoxicity improved in 2, 5 and 8. In general, the gold(III) complexes were more cytotoxic than those with platinum(II,IV). Several of these compounds proved to be more active than cisplatin and auranofin used as controls. The gold(III) complexes probably act by inhibiting the activity of thioredoxin reductase enzyme whereas the mode of action of the platinum(II,IV) complexes involves binding to DNA. Cells treated with the studied compounds presented morphological changes such as cell shrinkage and blebs formation, which indicate cell death by apoptosis induction.     

Oxidation and reduction of sulfite contribute to susceptibility and detoxification of SO2 in Populus × canescens leaves

Key Message

The critical level for SO ₂ susceptibility of Populus × canescens is approximately 1.2 μL L ^?1 SO ₂ . Both sulfite oxidation and sulfite reduction and assimilation contribute to SO ₂ detoxification.

Abstract

In the present study, uptake, susceptibility and metabolism of SO₂ were analyzed in the deciduous tree species poplar (Populus × canescens). A particular focus was on the significance of sulfite oxidase (SO) for sulfite detoxification, as SO has been characterized as a safety valve for SO₂ detoxification in herbaceous plants. For this purpose, poplar plants were exposed to different levels of SO₂ (0.65, 0.8, 1.0, 1.2 μL L^?1) and were characterized by visible injuries and at the physiological level. Gas exchange parameters (stomatal conductance for water vapor, CO₂ assimilation, SO₂ uptake) of the shoots were compared with metabolite levels (sulfate, thiols) and enzyme activities [SO, adenosine 5′-phosphosulfate reductase (APR)] in expanding leaves (80–90 % expanded). The critical dosage of SO₂ that confers injury to the leaves was 1.2 μL L^?1 SO₂. The observed increase in sulfur containing compounds (sulfate and thiols) in the expanding leaves strongly correlated with total SO₂ uptake of the plant shoot, whereas SO₂ uptake rate was strongly correlated with stomatal conductance for water vapor. Furthermore, exposure to high concentration of SO₂ revealed channeling of sulfite through assimilatory sulfate reduction that contributes in addition to SO-mediated sulfite oxidation to sulfite detoxification in expanding leaves of this woody plant species.     

Revision of Plerandra (Araliaceae). I. A synopsis of the genus with an expanded circumscription and a new infrageneric classification

Phylogenetic studies have demonstrated that Schefflera, the largest genus of Araliaceae, is grossly polyphyletic, comprising five distinct clades within the family. In an effort to establish monophyletic genera among the elements that currently comprise Schefflera, the genus Plerandra is expanded to encompass all of the members of one of these clades. In this synoptical revision, a new infrageneric classification is presented (along with a key) in which six subgenera are recognized. Four of these subgenera are newly described (Plerandra subgenera Canacoschefflera, Costatae, Gabriellarum, and Veilloniorum) and a fifth represents a new combination (Plerandra subg. Dizygotheca). A total of 33 species (one with two subspecies) are accepted, one of which is newly described (P. veilloniorum), and 22 new combinations are made (P. actinostigma, P. baillonii, P. cabalionii, P. costata, P. crassipes, P. elegantissima, P. elongata, P. emiliana, P. gabriellae, P. leptophylla, P. nono, P. osyana, P. osyana subsp. toto, P. pachyphylla, P. pancheri, P. plerandroides, P. polydactylis, P. reginae, P. seemanniana, P. tannae, P. vanuatua, P. veitchii). Neotypes are provided for six accepted names and one heterotypic synonym, and lectotypes are designated for 13 accepted names and 16 heterotypic synonyms. For each accepted species, full synonymy is provided along with geographic range and notes.     

Enhanced β-turn conformational stability of tripeptides containing ΔPhe in cis over trans configuration

Conformations of three pairs of dehydropeptides with the opposite configuration of the ΔPhe residue, Boc-Gly-Δ^Z/EPhe-Phe-p-NA (Z- p -NA and E- p -NA), Boc-Gly-Δ^Z/EPhe-Phe-OMe (Z-OMe and E-OMe), and Boc-Gly-Δ^Z/EPhe-Phe-OH (Z-OH and E-OH) were compared on the basis of CD and NMR studies in MeOH, TFE, and DMSO. The CD results were used as the additional input data for the NMR-based calculations of the detailed solution conformations of the peptides. It was found that Z- p -NA, E- p -NA, Z-OMe, and Z-OH adopt the β-turn conformations and E-OMe and E-OH are unordered. There are two overlapping type III β-turns in Z- p -NA, type II’ β-turn in E- p -NA, and type II β-turn in Z-OMe and Z-OH. The results obtained indicate that in the case of methyl esters and peptides with a free carboxyl group, Δ^ZPhe is a much stronger inducer of ordered conformations than Δ^EPhe. It was also found that temperature coefficients of the amide protons are not reliable indicators of intramolecular hydrogen bonds donors in small peptides.     

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.     

Development of SCAR marker for sex identification in dioecious Garcinia gummi-gutta

Key message

We have developed sex-specific SCAR marker for the identification of dioecious Garcinia gummi - gutta (L.), which is useful for the selection of G. gummi - gutta at seedling stage and for plantation programmes.

Abstract

Garcinia gummi-gutta (L.) Robs. is a dioecious fruit yielding tree, which is naturally distributed as well as cultivated in the orchards in Western Ghat regions of India. A sex-linked DNA fragment was identified in Garcinia gummi-gutta (L.) Robs. by screening 150 randomly amplified polymorphic DNA primers and only one of them (OPBD20) showed different amplification band pattern associated with sex type. This sex-linked fragment was converted into male-specific sequence-characterized amplified region (SCAR) marker, CAM-566. The primers deigned in this study (OPBD20F and OPBD20R) correctly differentiated 12 male and 12 female plants at high annealing temperatures. Thus, a 556-bp band was amplified in male samples but not in female ones. Nevertheless, it should be noted that the fragments from both sexes were amplified at relatively low annealing temperatures. Additionally, the developed SCAR marker successfully identified the sexes of ten sex-unknown samples. Therefore, it can be used as an effective, convenient and reliable tool for sex determination in such dioecious species.     

Synthesis of Pyrrolo[2′,3′:4,5]Furo[3,2-c]Pyridine-2-Carboxylic Acids

1H-Pyrrolo[2′,3′:4,5]furo[3,2-c]pyridine-2-carboxylic acid (6a) and its 1-methyl (6b) and 1-benzyl (6c) derivatives were synthesized. 3-(5-Methoxycarbonyl-4H-furo[3,2-b]-pyrrole-2-yl)propenoic acid (1) was converted to the corresponding azide 2, which in turn was cyclized to give 3 by heating in diphenylether. The pyridone 3 obtained was aromatized with phosphorus oxychloride, then reduced with zinc in acetic acid to give methyl 1H-pyrrolo[2′,3′:4,5]furo[3,2-c]pyridine-2-carboxylate (5), which by hydrolysis gave the corresponding carboxylic acid 6a.     

New genera and species of ericaceae (Vaccinieae) from Costa Rica and Panama

Two new monotypic genera,Didonica andUtleya, are described, withD. pendula from Panama andU. costaricensis from Costa Rica.Disterigma trimera (Panama),D. utleyorum (Costa Rica, Panama, Colombia, and Ecuador),Lateropora santafeensis (Panama),Lysiclesia panamensis (Panama),Macleania talamancensis (Costa Rica),Themistoclesia costaricensis (Costa Rica) andT. horquetensis (Panama),Vaccinium costaricense andV. orosiense (both from Costa Rica) and V.jefense (Panama) are all described as new. New combinations are provided for the PanamanianVaccinium floccosum (=Symphysia floccosa) and the West IndianVaccinium racemosum (=Symphysia racemosa). Keys are provided for the Central American species ofDisterigma andThemistoclesia, the species ofLateropora andLysiclesia, and the Costa Rican and Panamanian species ofVaccinium. Six new species are illustrated.     

New taxa and nomenclatural changes in arceuthobium (viscaceae)

The following new taxa are recognized inArceuthobium: subgeneraArceuthobium andVaginata; sectionsVaginata, Campylopoda, andMinuta; seriesCampylopoda,Rubra, andStricta; speciesA. apachecum,A. californicum,A. guatemalense,A. hondurense, andA. pini; new formae spécialesA. abietinum f. sp.concoloris,A. abietinum f. sp.magnificae. New combinations:A. abietinum (Engelm.) Hawksworth & Wiens, andA. microcarpum (Engelm.) Hawksworth & Wiens.     

Characterization of the sugar-O-methyltransferase LobS1 in lobophorin biosynthesis

Lobophorins A (1) and B (2) belong to a large group of spirotetronate natural products with potent antibacterial and antitumor activities. The cloning of the lobophorin biosynthesis gene cluster from the deep-sea-derived Streptomyces sp. SCSIO 01127 identified a sugar-O-methyltransferase-encoding gene lobS1. The lobS1 inactivation mutant accumulated two new lobophorin analogs 3 and 4, different from 1 and 2 by lacking the 4-methyl group at the terminal l-digitoxose, respectively. Biochemical experiments verified that LobS1 was a SAM-dependent sugar-O-methyltransferase that required divalent metal ions for better activity. Antibacterial assays revealed compounds 3 and 4 were generally less potent than compounds 1 and 2. These findings suggest that the methylation on the terminal digitoxose by LobS1 tailors lobophorin biosynthesis and highlights the importance of this methylation for antibacterial potence.