Persistence of fungitoxicity of two triorganotin(IV) compounds in soil

The persistence of triphenyltin chloride-triphenylphosphine oxide (Ph₃SnCl·Ph₃PO) and diphenylbutyltin bromide (Ph₂BuSnBr) in unsterilized sandy loam soil maintained in the dark at 60% of its water-holding capacity and at 27±2°C was studied over a period of 29 days. The percentage recovery of the compounds upon extraction with acetone immediately after application to soil was 60% for Ph₃SnCl·Ph₃PO and 9.8% for Ph₂BuSnBr. The half-lives of the compounds were 15 days for Ph₃SnCl·Ph₃PO and 14.2 days for Ph₂BuSnBr. After 29 days following application of the compounds in soil < 8.3 μg g^?1 of Ph₃SnCl·Ph₃PO and < 5.1 μg g^?1 of Ph₂BuSnBr remained in soil compared with the starting concentration of 50 μg of each compound per gram soil. The two triorganotin compounds were evidently easily degraded and the compounds may be applied every 2–3 weeks in the field at a rate of at least 0.005–0.01 kg ha^?1.     

Efficacy of selected triorganotin(IV) compounds on leaves against Phytophthora palmivora (Butler) Butler isolated from black pepper and cocoa

Several triorganotin(IV) compounds and Terrazole® 35 WP were screened for their in vitro antifungal activity against three isolates of Phytophthora palmivora. Two isolates (isolates Phy. 2 and Phy. 334) were obtained from black pepper (Piper nigrum L.) and one isolate (isolate Phy. 56) from cocoa leaves (Cacao theobromae). ED₅₀ values for radial growth of the isolates ranged from 0.09 to 1,700 μg cm^?3 for the triorganotin(IV) compounds and from 3.46 to 1 227 000 μg cm^?3 for Terrazole®. Diphenylbutyltin bromide exhibited the highest antifungal activity against the three isolates of P. palmivora with ED₅₀ values ranging from 0.30 to 0.73 μg cm^?3. Diphenylbutyltin bromide was equally effective against a freshly isolated virulent culture of P. palmivora (isolate Phy. 346) from black pepper leaves in Sarawak, East Malaysia, yielding an ED₅₀ value for radial growth of 0.87 μg cm^?3 and a probit-log concentration regression line slope value of 1.04. In vitro efficacy of diphenylbutyltin bromide against isolate Phy. 346 using detached healthy pepper leaves showed 40–75% infection of leaves at 100 μg cm^?3 and no infection at 500 μg cm^?3. Diphenylbutyltin bromide at 100 μg cm^?3, however, inhibited the diameter of lesion by 43.3–73.7% compared with the untreated controls. Black pepper leaves treated with Terrazole® at 778 μg cm^?3 exhibited 5.3–33.3% inhibition of lesion diameter compared with the untreated controls, where 90–100% of the leaves were infected. Concentrations of diphenylbutyltin bromide of 1000–2500 μg cm^?3 caused some injury lesions on the leaves. From the results obtained, it appears that diphenylbutyltin bromide could be used as a protective spray or drench against P. palmivora infection of black pepper at 100–500 μg cm^?3.     

Studies on the phytotoxic effects of some organotin(IV) compounds on the germination of the mung bean seed,Phaseolus aureus

A selected range of organotin(IV) compounds of formula R_xSnX_4-x (x = 2 or 3; R = alkyl, cycloalkyl or aryl), as well as the adducts, (p-ZC₆H₄)₃SnCl. Ph₃PO (Z = H, Me) were examined in vivo for their phytotoxic effects relative to the more powerful s-triazine herbicides against the mung bean seed, Phaseolus aureus. Phytotoxicity was assessed in terms of changes in (a) weights of primary leaves, (b) weights of cotyledons, (c) seedling heights and (d) root morphology. The triorganotin compounds were more phytotoxic than the diorganotins, and within the R₃Sn structural class, inhibitory potency was greater for alkyltins than for aryltins. Decreasing the alkyl chain lengths or placing electrondonating substituents on the aromatic rings increased the phytotoxicity. A significant phytotoxic effect, comparable with that of Ph₃SnCl, was manifested by tricyclohexyltin chloride, in marked contrast to the well-known low phytotoxicity of tricyclohexyltin hydroxide. Using Ph₃SnCl as the model compound, it was further demonstrated that the total chlorophyll content decreased with increasing concentration of Ph₃SnCl, but the ration of chlorophyll a to chlorophyll b was constant. It was also found that tin uptake in the seedlings was directly proportional to Ph₃SnCl test concentrations; the magnesium and iron levels in the treated seedlings, however, were unchanged relative to the control.     

Evaluation of the Structure–Activity Relationship of Rifabutin and Analogs: A Drug–Membrane Study

This work focuses on the influence of rifabutin and two novel analogs, namely, N′‐acetyl‐rifabutin and N′‐butanoyl‐rifabutin, on the biophysical properties of lipid membranes. Monolayers and multilamellar vesicles composed of egg L ‐α‐phosphatidylcholine:cholesterol in a molar ratio of 4:1 are chosen to mimic biological membranes. Several accurate biophysical techniques are used to establish a putative relationship between the chemical structure of the antimycobacterial compounds and their activity on the membranes. A combination of in situ experimental techniques, such as Langmuir isotherms, Brewster angle microscopy, polarization‐modulated infrared reflection–absorption spectroscopy, and small‐angle X‐ray scattering, is used to assess the drug–membrane interaction. A relationship between the effect of a drug on the organization of the membranes and their chemical structure is found and may be useful in the development of new drugs with higher efficacy and fewer toxic effects.     

Vaulted Biaryls in Catalysis: A Structure–Activity Relationship Guided Tour of the Immanent Domain of the VANOL Ligand

The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate) that is assembled in situ from three equivalents of B(OPh)₃ and one of the VANOL ligand by a molecule of substrate. The substrates are bound to the boroxinate by H bonds to oxygen atoms O1–O3. The effects of introducing substituents at each position of the naphthalene core of the VANOL ligand are systematically investigated in an aziridination reaction. Substituents in the 4,4′‐ and 8,8′‐positions have a negative effect on catalyst performance, whereas, substituents in the 7‐ and 7′‐positions have the biggest impact in a positive direction.     

Effect of six triorganotin(IV) compounds on nitrification and ammonification in soil

The effects of six triorganotin(IV) compounds and of Thiram on nitrification and ammonification in soil were investigated. Low concentrations of up to 50 μg g^?1 of the triorganotin(IV) compounds enhanced nitrate-nitrogen (NO₃^?-N) production in soil. Except for diphenylbutyltin bromide, which inhibited nitrification at 250 μg g^?1, the other triorganotin(IV) compounds were inhibitory at concentrations of 100 μg g^?1 to less than 250 μg g^?1. At 10 μg g^?1, only triphenyltin acetate was less inhibitory towards nitrification compared with Thiram. At 250 μg g^?1, Thiram exerted a strongly persistent inhibitory effect towards nitrification. The NO₃^?-N level recorded 28 days after application was only 0.10 μg g^?1 soil. With the triorganotin compounds NO₃^?-N levels of 7.05–12.06 μg g^?1 soil were recorded 28 days following their application. The deleterious effects of the triorganotin(IV) compounds were less persistent and recovery of nitrification was evident seven days after application. Low concentrations of Thiram and triorganotin(IV) compounds inhibited ammonification, whereas higher concentrations enhanced ammonification. Complete inhibition of ammonification was attained 21–28 days after application of Thiram at 50 μg g^?1. On the other hand, with the triorganotin(IV) compounds, except for diphenylbutyltin bromide at 10–50 μg g^?1, ammonification persisted at all concentrations 28 days after application.     

A New Iron‐Based Carbon Monoxide Oxidation Catalyst: Structure–Activity Correlation

A new iron‐based catalyst for carbon monoxide oxidation, as a potential substitute for precious‐metal systems, has been prepared by using a facile impregnation method with iron tris‐acetylacetonate as a precursor on γ‐Al₂O₃. Light‐off and full conversion temperatures as low as 235 and 278 °C can be reached. However, the catalytic activity strongly depends on the loading; lower loadings perform better than higher ones. The different activities can be explained by variations of the structures formed. The structures are thoroughly characterized by a multimethodic approach by using X‐ray diffraction, Brunauer–Emmett–Teller surface areas, and Mössbauer spectroscopy combined with diffuse reflectance UV/Vis and X‐ray absorption spectroscopy. Consequently, isolated tetrahedrally coordinated Fe³⁺ centers and phases of AlFeO₃ are identified as structural requirements for high activity in the oxidation of carbon monoxide.     

Structure–Activity Relationship of Palladium Phosphanesulfonates: Toward Highly Active Palladium‐Based Polymerization Catalysts

Palladium phosphanesulfonate [R₂P(C₆H₄‐o‐SO₃)PdMeL] catalysts permit the copolymerization of an exceptional large number of functional olefins with ethylene. However, these catalysts usually have reduced activity. We here have conducted a systematic study on the influence of the phosphane substituent, R, on activity and molecular weight. Phosphanes with strong σ‐donating character are shown to lead to the most active catalysts. Thus, the catalyst based on phosphane bis‐tert‐butyl‐phosphanyl‐benzenesulfonic acid (R=tBu) exhibits unprecedented high activity, rapidly polymerizing ethylene at room temperature to yield a linear polymer of high molecular weight (M_w=116 000 g mol^?1). The influence of the R group on the catalyst ability to incorporate methyl acrylate is also investigated.     

Structure–activity relationship of N‐heterocyclic carbene–Pd(II)–imidazole complexes in Suzuki–Miyaura coupling between 4‐methoxyphenyl chloride and phenylboronic acid

A series of N‐heterocyclic carbene–PdCl₂–imidazole [NHC–Pd(II)–Im] complexes were synthesized and the structure of most of them was unambiguously determined by X‐ray single‐crystal diffraction. The structure–activity relationship of these complexes was investigated for the Suzuki–Miyaura coupling between 4‐methoxyphenyl chloride and phenylboronic acid, and the effect of the NHCs and Im moieties were fully discussed. The sterically hindered IPr‐based complex showed the highest catalytic activity. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and Structure–Activity Relationship of Vicenistatin,a Cytotoxic 20‐Membered Macrolactam Glycoside

We have developed two syntheses of vicenistatin and its analogues. Our first‐generation strategy included the rapid and sequential assembly of the macrocyclic lactam by using an intermolecular Horner–Wadsworth–Emmons reaction between the C3–C13 fragment and the C1–C2, C14–C19 fragment, followed by an intramolecular Stille coupling reaction. The second‐generation strategy utilized a ring‐closing metathesis of a hexaene intermediate to generate the desired 20‐membered macrolactam. This second‐generation strategy made it possible to prepare synthetic analogues of vicenistatin, including the C20‐ and/or C23‐demethyl analogues. Evaluation of the cytotoxic effect of these analogues indicated the importance of the fixed conformation of aglycon for determining the biological activity of the vicenistatins.     

Alphabet‐Inspired Design of (Hetero)Aromatic Push–Pull Chromophores

Push–pull molecules represent a unique and fascinating class of organic π‐conjugated materials. Herein, we provide a summary of their recent extraordinary design inspired by letters of the alphabet, especially focusing on H‐, L‐, T‐, V‐, X‐, and Y‐shaped molecules. Representative structures from each class were presented and their fundamental properties and prospective applications were discussed. In particular, emphasis is given to molecules recently prepared in our laboratory with T‐, X‐, and Y‐shaped arrangements based on indan‐1,3‐dione, benzene, pyridine, pyrazine, imidazole, and triphenylamine. These push–pull molecules turned out to be very efficient charge‐transfer chromophores with tunable properties suitable for second‐order nonlinear optics, two‐photon absorption, reversible pH‐induced and photochromic switching, photocatalysis, and intercalation.

     

Highly Emissive Diborylphenylene‐Containing Bis(phenylethynyl)benzenes: Structure–Photophysical Property Correlations and Fluoride Ion Sensing

A series of 2,5‐bis(dimesitylboryl)‐1,4‐bis(arylethynyl)benzenes 1 – 6 that contain various p‐substituents on the terminal benzene rings, including NPh₂ ( 1 ), OMe ( 2 ), Me ( 3 ), H ( 4 ), CF₃ ( 5 ), and CN ( 6 ) groups, were synthesized, and the effects of the p‐substituents on the absorption and fluorescence properties were investigated both in solution and in the solid state. Linear relationships were obtained not only between the Hammett σ_p⁺ constants of the p‐substituents and the absorption and fluorescence maxima, quantum yields, and excited‐state dynamics parameters in solution, but also between the σ_p⁺ constants and the fluorescence quantum yields in the solid state. An important finding extracted from these results is that the suppressed fluorescence quenching in the solid state is a common feature for the present laterally boryl‐substituted π‐conjugated skeletons. Hence, the diborylphenylene can serve as a useful core unit to develop highly emissive organic solids. In fact, most of the derivatives showed more intense emission in the solid state than in solution. In addition to these studies, the titration experiment of 1 by the addition of nBu₄NF was conducted, which showed the stepwise bindings of two fluoride ions with high association constants as well as a drastic change in the fluorescence spectra, while constantly maintaining high quantum yields (0.61–0.76), irrespective of the binding modes. This result also demonstrated the potential utility of the present molecules as an efficient fluorescent fluoride ion sensor.     

Identification of Structure–Activity Relationships from Screening a Structurally Compact DNA‐Encoded Chemical Library

Methods for the rapid and inexpensive discovery of hit compounds are essential for pharmaceutical research and DNA‐encoded chemical libraries represent promising tools for this purpose. We here report on the design and synthesis of DAL‐100K, a DNA‐encoded chemical library containing 103 200 structurally compact compounds. Affinity screening experiments and DNA‐sequencing analysis provided ligands with nanomolar affinities to several proteins, including prostate‐specific membrane antigen and tankyrase 1. Correlations of sequence counts with binding affinities and potencies of enzyme inhibition were observed and enabled the identification of structural features critical for activity. These results indicate that libraries of this type represent a useful source of small‐molecule binders for target proteins of pharmaceutical interest and information on structural features important for binding.     

A Quantitative Structure–Activity Relationship Study of Calpeptin (Calpain Inhibitor) as an Anticancer Agent

Calpeptin analogs show anticancer properties with inhibition of calpain. In this work, we applied a quantitative structure–activity relationship (QSAR) model on 34 calpeptin derivatives to select the most appropriate compound. QSAR was employed to generate the models and predict the more significant compounds through a series of calpeptin derivatives. The HyperChem, Gaussian 09, and Dragon software programs were used for geometry optimization of the molecules. The 2D and 3D molecular structures were drawn by ChemDraw (Ultra 16.0) and Chem3D (Pro16.0) software. The Unscrambler program was used for the analysis of data. Multiple linear regression (MLR‐MLR), partial least‐squares (MLR‐PLS1), principal component regression (MLR‐PCR), a genetic algorithm‐artificial neural networks (GA‐ANN), and a novel similarity analysis‐artificial neural network (SA‐ANN) method were used to create QSAR models. Among the three MLR models, MLR‐MLR provided better statistical parameters. The R² and RMSE of the prediction were estimated as 0.8248 and 0.26, respectively. Nevertheless, the constructed model using GA‐ANN revealed the best statistical parameters among the studied methods (R² test = 0.9643, RMSE test = 0.0155, R² train = 0.9644, RMSE train = 0.0139). The GA‐ANN model is found to be the most favorable method among the statistical methods and can be employed for designing new calpeptin analogs as potent calpain inhibitors in cancer treatment.     

Selective Inhibition of the Immunoproteasome by Structure‐Based Targeting of a Non‐catalytic Cysteine

Clinically applied proteasome inhibitors induce cell death by concomitant blockage of constitutive and immunoproteasomes. In contrast, selective immunoproteasome inhibition is less cytotoxic and has the potential to modulate chronic inflammation and autoimmune diseases. In this study, we rationally designed decarboxylated peptides that covalently target a non‐catalytic cysteine of the immunoproteasome subunit β5i with α‐chloroacetamide‐containing sidechains. The enhanced isoform specificity decreased cytotoxic effects and the compound suppressed the production of inflammatory cytokines. Structure‐based optimization led to over 150‐fold selectivity for subunit β5i over β5c. This new compound class provides a promising starting point for the development of selective immunoproteasome inhibitors as potential anti‐inflammatory agents.     

From Low to Very High Birefringence in Bis(2‐pyridylimino)isoindolines: Synthesis and Structure–Property Analysis

A series of new substituted 1,3‐bis(2‐pyridylimino)isoindolines—1,3‐bis(2‐pyridylimino)‐5,6‐bis(2,6‐diisopropylphenoxy)isoindoline ( 2 b ), 1,3‐bis(2‐pyridylimino)‐5,6‐bis(4‐tert‐butylphenyl)isoindoline ( 2 c ), and 1,3‐bis(2‐pyridylimino)‐5‐tert‐butylisoindoline ( 2 d )—were synthesized and structurally characterized by single‐crystal X‐ray diffraction. The birefringence (Δn) of the crystals of unsubstituted 1,3‐bis(2‐pyridylimino)isoindoline ( 2 a ), 2 b , 2 c , and 2 d were measured and found to vary greatly, with Δn values of 0.0654(3), 0.0629(17), 0.588(10), 0.701(12), respectively. A structure–property relationship for the birefringence values of 2 a – 2 d was outlined and indicated that the anisotropy of the polarizability of the molecules plays a crucial role in the birefringence of the crystals. The greatest birefringence values are achieved when the molecules are oriented in a face‐to‐face configuration intermolecularly, and along the crystallographic face being measured.