Small Alkyl Research Articles

A study of the molecular interactions between ammonium-based ionic liquids and N,N-dimethylacetamide

In this work, we report the molecular interactions of different cation alkyl chain lengths with same anion of ammonium-based ionic liquids (ILs) such as tetraethylammonium hydroxide (TEAH), tetrapropylammonium hydroxide (TPAH) and tetrabutylammonium hydroxide (TBAH) with N,N-dimethylacetamide (DMA) through thermophysical properties with varying the compositions of ILs at different temperatures from 25 to 40°C under atmospheric pressure. Experimental densities (ρ), ultrasonic sound velocities (u), viscosities (η) and refractive indices (nD) of binary mixtures of ILs with DMA are measured over the wide composition range. The excess molar volumes (VE), deviation in isentropic compressibilities (Δκs), deviation in viscosities (Δη) and deviation in refractive indices (ΔnD) are calculated from experimental values and are correlated by Redlich-Kister polynomial equations. Consequently, VE values show that negative for small cation alkyl chain length of ammonium-based ILs as compared to large cation alkyl chain length of ILs. We have observed the strength of intermolecular interactions such as hydrogen bonding, ion-ion pair interactions and induced dipole interactions between the ions of ammonium-based ILs with DMA from obtained data. Thermophysical properties, however, possessed by these binary systems are exceedingly promising and predictable that these systems will find applications in chemical industry.

Discovery of enantioselectivity of urea inhibitors of soluble epoxide hydrolase

Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) in the metabolic pathway of arachidonic acid and has been considered as an important therapeutic target for chronic diseases such as hypertension, diabetes and inflammation. Although many urea derivatives are known as sEH inhibitors, the enantioselectivity of the inhibitors is not highlighted in spite of the stereoselective hydrolysis of EETs by sEH. In an effort to explore the importance of enantioselectivity in the urea scaffold, a series of enantiomers with the stereocenter adjacent to the urea nitrogen atom were prepared. The selectivity of enantiomers of 1-(α-alkyl-α-phenylmethyl)-3-(3-phenylpropyl)ureas showed wide range differences up to 125 fold with the low IC50 value up to 13 nM. The S-configuration with planar phenyl and small alkyl groups at α-position is crucial for the activity and selectivity. However, restriction of the free rotation of two α-groups with indan-1-yl or 1,2,3,4-tetrahydronaphthalen-1-yl moiety abolishes the selectivity between the enantiomers, despite the increase in activity up to 13 nM. The hydrophilic group like sulfonamido group at para position of 3-phenylpropyl motif of 1-(α-alkyl-α-phenylmethyl-3-(3-phenylpropyl)urea improves the activity as well as enantiomeric selectivity. All these ureas are proved to be specific inhibitor of sEH without inhibition against mEH.

Physicochemical characterization of a new family of small alkyl phosphonium imide ionic liquids

Despite their promising properties, phosphonium based ionic liquids have attracted little attention as compared to their nitrogen-based cation counterparts. This study focuses on the properties of a family of small phosphonium imide ionic liquids, as well as the effect of lithium salt addition to these. The 6 ionic liquids were either alkyl, cyclic or nitrile functionalised phoshonium cations with bis(trifluoromethanesulfonyl)imide, NTf2, or bis(fluorosulfonyl)imide (FSI) as anion. Amongst the properties investigated were ionic conductivity, viscosity, thermal behaviour, electrochemical stability and the reversibility of electrochemical lithium cycling. All ionic liquids showed very promising properties e.g. having low transition temperatures, high electrochemical stabilities, low viscosities and high conductivities. Particularly the trimethyl phosphonium ionic liquids showed some of the highest conductivities reported amongst phosphonium ionic liquids generally. The combination of electrochemical stability, high conductivity and reversible lithium cycling makes them promising systems for energy storage devices such as lithium batteries.

New mesogenic compounds possessing a biphenyl ester and ether moiety comprising 1,3-dimethylbarbituric acid: synthesis, characterisation and mesomorphic studies

ABSTRACTNew substituted derivatives of 5-vinyl-1,3-dimethylbarbituric acid were synthesised and evaluated for liquid crystal properties. Two sets of molecules were prepared. One end of all the molecules possesses the 1,3-dimethylbarbituric core. The first set comprises biphenyl ethers, 4a–n and the second set biphenyl esters, 5a–g. Liquid crystalline properties were investigated by POM and DSC techniques. All the compounds exhibited enantiotropic smectic A and nematic mesophases. The LC properties were found to depend on the spacer and terminal alkoxy- chain and alkoxy- ester moiety of the molecules. Smaller alkyl chain members showed a smectic phase, while higher alkyl chain members showed a nematic phase.

Differentiation of cyclic tertiary amine cathinone derivatives by product ion electron ionization mass spectrometry.

A number of synthetic cathinones (aminoketones, 'bath salts') are tertiary amines containing a cyclic amino group, most commonly pyrrolidine. These totally synthetic compounds can be prepared in a number of regioisomeric designer modifications and many of these can yield isomeric major fragment ions in electron ionization mass spectrometry (EI-MS). A series of regioisomeric cyclic tertiary amines were prepared and evaluated in EI-MS and MS/MS product ion experiments. The cyclic amines azetidine, pyrrolidine, piperidine and azepane were incorporated into a series of aminoketones related to the cathinone derivative drug of abuse known as MDPV. Deuterium labeling in both the cyclic amine and alkyl side chain allowed for the confirmation of the structure for the major product ions formed from the EI-MS iminium cation base peaks. These iminium cation base peaks show characteristic product ion spectra which allow differentiation of the ring and side-chain portions of the structure. The small alkyl side chains favor ring fragmentation in the formation of the major product ions. The higher side-chain homologues appear to promote product ion formation by side-chain fragmentation. Both side-chain and ring fragmentation yield a mixture of product ions in the piperidine and azepane series. Product ion fragmentation provides useful data for differentiation of cyclic tertiary amine iminium cations from cathinone derivative drugs of abuse. Regioisomeric iminium cations of equal mass yield characteristic product ions for the alkyl side-chain homologues of azetidine, pyrrolidine, piperidine and azepane cyclic amines.

Preservation of Neural Sensitivity after Noise-Induced Suppression of Sensory Function.

Permanent loss of outer hair cell (OHC) amplification may occur within days of acoustic overexposure. This loss of sensory function typically results in an immediate loss of neural sensitivity although neurodegeneration occurs months or years after damage to OHCs. This delay in neurodegeneration might provide an opportunity to preserve neural sensitivity although OHC amplification is permanently lost. To test the hypothesis that neural functions can be preserved after permanent and severe loss of OHC amplification. To begin to address this possibility, an animal model of severe permanent loss of both OHC and neural functions was established. This research employed a 4 × 4 split-plot factorial design, with four levels of the within-subject factor (time: baseline, 1-day, 1-week, and 1-mo postnoise exposure) and four levels of the between-subject factor (experimental groups: control, noise exposed, therapy, and noise exposed + therapy). Twenty-six hooded male Long-Evans rats (263 ± 63 g) served as subjects for this experiment. All animals exhibited baseline auditory function that approximated normative values for rats of the same strain. Distortion product otoacoustic emissions and auditory brainstem responses were used to assay and differentiate OHC versus neural functions. Factorial analysis of variances was computed to identify statistically significant main effects and Dunnett testing was employed in post hoc computations. To rescue neural function after permanent loss of OHC amplification, small molecular weight carboxy alkyl esters were employed after noise injury. The results revealed that in the presence of permanent loss of OHC amplification, the loss of neural sensitivity could be rescued. In addition, auditory brainstem response wave I amplitudes at suprathreshold levels were rescued from noise-induced depletion into the biologic noise floor. Since mammalian OHCs do not regenerate after damage, these results encourage further experiments aimed at preserving neural functions following noise injury.

Synthesis, Antimalarial Activity Evaluation and Drug likeness Study of Some New Quinoline-Lawsone Hybrids

In the present study, a new series of quinoline-lawsone hybrid compounds were synthesized and evaluated in vitro for their antimalarial effectiveness. Several aliphatic and aromatic/heteroaromatic diamines were used as connecting/bridge moiety between the 7-chloro-4-aminoquinoline and 3-amino-1, 4-naphthoquinone pharmacophoric scaffolds. The molecular properties of hybrid compounds were also studied in silico for drug-likeness assessment based on Lipinski’s rule of five. Results of antimalarial activity reveal that all the tested compounds showed activity against both chloroquine sensitive (RKL-2) and chloroquine resistant (RKL-9) strains of Plasmodium falciparum which was considerably less as compared to the standard drug, chloroquine. All the compounds exhibited same degree of activity at the tested dose against sensitive strain with IC50 values 0.391-1.033 µg/ml. Furthermore, four compounds which were additionally tested against resistant strain also showed activity with IC50 values from 0.684-1.778 µg/ml at the same dose. The IC50 values for CQ against sensitive and resistant strains of P. falciparum were found to be 0.0391 µg/ml and 0.305 µg/ml, respectively. From results it is apparent that the compound with a small alkyl bridge moiety diaminoethyl possesses better activity profile against both sensitive and resistant strains (IC50=0.391 and 0.684 µg/ml, respectively) than rest of the synthesized analogues. The results of drug-likeness studies showed that all newly designed quinoline-lawsone hybrids possess good drug-like properties, indicating their drug-likeness behaviour is favourable for optimal antimalarial action. Assessment of drug-likeness score further implies the suitability of hybrid derivatives as drug-like molecules.

Synthesis of Cembranoid Analogues through Ring-Closing Metathesis of Terpenoid Precursors: A Challenge Regarding Ring-Size Selectivity.

A systematic study on ring-closing metathesis with Grubbs II catalyst to cembranoid macrocycles is described. Acyclic terpenoids with a functional group X in the homoallylic position relative to an RCM active terminus and substituents R, R(1) directly attached to the other terminal double bond were prepared from geraniol derived trienes and fragments that are based on bromoalkenes and dimethyl malonate. Such terpenoids were suitable precursors, despite the presence of competing double bonds in their framework. The size of R and R(1) is crucial for successful macrocyclization. Whereas small alkyl substituents at the double bond directed the RCM towards six-membered ring formation, cross metathesis leading to dimers dominated for bulkier alkyl groups. A similar result was obtained for precursors without functional group X. In the case of unsymmetrically substituted terpenoid precursor (R = Et, R(1) = Me) with homoallylic OTBS or OMe group, the RCM could be controlled towards formation of macrocyclic cembranoids, which were isolated with excellent E-selectivity. The role of the substituents was further studied by quantum chemical calculations of simplified model substrates. Based on these results a mechanistic rationale is proposed.

Rigidified A3 Adenosine Receptor Agonists: 1-Deazaadenine Modification Maintains High in Vivo Efficacy.

Substitution of rigidified A3 adenosine receptor (AR) agonists with a 2-((5-chlorothiophen-2-yl)ethynyl) or a 2-(4-(5-chlorothiophen-2-yl)-1H-1,2,3-triazol-1-yl) group provides prolonged protection in a model of chronic neuropathic pain. These agonists contain a bicyclo[3.1.0]hexane ((N)-methanocarba) ring system in place of ribose, which adopts a receptor-preferred conformation. N (6)-Small alkyl derivatives were newly optimized for A3AR affinity and the effects of a 1-deaza-adenine modification probed. 1-Deaza-N (6)-ethyl alkyne 20 (MRS7144, K i 1.7 nM) and 1-aza N (6)-propyl alkyne 12 (MRS7154, K i 1.1 nM) were highly efficacious in vivo. Thus, the presence of N1 is not required for nanomolar binding affinity or potent, long-lasting functional activity. Docking of 1-deaza compounds to a receptor homology model confirmed a similar binding mode as previously reported 1-aza derivatives. This is the first demonstration in nonribose adenosine analogues that the 1-deaza modification can maintain high A3AR affinity, selectivity, and efficacy.

Naltrindole derivatives with fluorinated ethyl substituents on the 17-nitrogen as δ opioid receptor inverse agonists.

We synthesized derivatives of the δ opioid receptor (DOR) antagonists naltrindole (NTI) and compound 1 that were modified with small alkyl or fluorinated ethyl substituents on the 17-nitrogen. Although the derivatives showed decreased binding affinities for the opioid receptors, their selectivities for the DOR were higher than the parent compounds NTI and compound 1. Surprisingly, 17-fluoroethyl NTI derivatives exerted DOR inverse agonistic activities. The DOR inverse agonism of compounds 4c-e was less efficacious but significant, as compared with a standard DOR inverse agonist ICI-174864. On the other hand, compound 1 and its derivatives with small alkyl or monofluoroethyl substituents were partial agonists, but the derivatives having di- or trifluoroethyl group showed neither agonistic nor inverse agonistic activities.

New approaches to the synthesis of canthin-4-one alkaloids and synthetic analogues

Two novel approaches to the canthin-4-one ring system have been worked out. Claisen-type condensation of 1-acetyl-β-carboline with N-acyl benzotriazoles gives, via intermediate 1,3-diketones, 6-alkylcanthin-4-ones in one single operation, but this protocol is restricted to small alkyl substituents. An alternative approach, via 1-ethynyl-β-carboline and 1-isoxazolyl-β-carbolines, followed by reductive isoxazole cleavage and cyclization, is more versatile. 5,6-disubstituted canthin-4-ones are accessible via iodination at C-5 and subsequent Pd-catalyzed cross-coupling.

SAR refinement of antileishmanial N2,N4-disubstituted quinazoline-2,4-diamines

Visceral leishmaniasis is a neglected parasitic disease that has a high fatality rate in the absence of treatment. New drugs that are inexpensive, orally active, and effective could be useful tools in the fight against this disease. We previously showed that N2,N4-disubstituted quinazoline-2,4-diamines displayed low- to sub-micromolar potency against intracellular Leishmania, and lead compound N4-(furan-2-ylmethyl)-N2-isopropyl-7-methylquinazoline-2,4-diamine (4) exhibited modest efficacy in an acute murine model of visceral leishmaniasis. In the present work, thirty-one N2,N4-disubstituted quinazoline-2,4-diamines that had not previously been examined for their antileishmanial activity were evaluated for their potency and selectivity against Leishmania donovani, the causative parasite of visceral leishmaniasis. Quinazoline-2,4-diamines with aromatic substituents at both N2 and N4 exhibited potent in vitro antileishmanial activity but relatively low selectivity, while compounds substituted with small alkyl groups at either N2 or N4 generally showed lower antileishmanial potency but were less toxic to a murine macrophage cell line. Based on their in vitro antileishmanial potency, N4-benzyl-N2-(4-chlorobenzyl)quinazoline-2,4-diamine (15) and N2-benzyl-N4-isopropylquinazoline-2,4-diamine (40) were selected for in vivo evaluation of their pharmacokinetic and antileishmanial properties. While 15 displayed a longer plasma half-life and a greater area under the curve than 40, both compounds showed low efficacy in an acute murine visceral leishmaniasis model. Although the present study did not identify new quinazoline-2,4-diamines with promising in vivo efficacy, the reduced in vitro toxicity of derivatives bearing small alkyl groups at either N2 or N4 may provide clues for the design of safe and effective antileishmanial quinazolines.

An Experimental and Kinetic Modeling Study of Premixed Laminar Flames of Methyl Pentanoate and Methyl Hexanoate

Abstract Detailed chemical structures of stoichiometric and rich premixed laminar flames of methyl pentanoate and methyl hexanoate were investigated over a flat burner at 20 Torr and for methyl pentanoate at 1 atm. Molecular beam mass spectrometry was used with tunable synchrotron vacuum ultraviolet (VUV) photoionization for low pressure flames of both methyl pentanoate and methyl hexanoate, and soft electron-impact ionization was used for atmospheric pressure flames of methyl pentanoate. Mole fraction profiles of stable and intermediate species, as well as temperature profiles, were measured in the flames. A detailed chemical kinetic high temperature reaction mechanism for small alkyl ester oxidation was extended to include combustion of methyl pentanoate and methyl hexanoate, and the resulting model was used to compare computed values with experimentally measured values. Reaction pathways for both fuels were identified, with good agreement between measured and computed species profiles. Implications of these results for future studies of larger alkyl ester fuels are discussed.

Pentacyclic triterpene derivatives possessing polyhydroxyl ring A inhibit Gram-positive bacteria growth by regulating metabolism and virulence genes expression

The hydroxyl group in ring A of pentacyclic triterpene is essential for antibacterial activity. Pentacyclic triterpenes bearing three hydroxyl groups in ring A were mainly found in plants and displayed significant antibacterial activity. However, no study reported how to obtain this type of compounds by chemical modification. In this study, twenty-five new pentacyclic triterpenes bearing polyhydroxyl ring A were synthesized from parental compounds ursolic acid (UA) and oleanolic acid (OA). Here, we showed that most of these derivatives displayed a significantly increased activity against Gram-positive bacteria compared to parental compounds in vitro. Some of these compounds exhibited minimum inhibitory concentration values of 1–3-fold more potent than the positive controls. The structure–activity relationship studies demonstrated that introducing two hydroxyl groups at positions C-1 and C-2 together with a small alkyl ester group at C-17 of UA and OA strongly enhanced growth-inhibiting activity against Gram-positive bacteria. The antibacterial mechanism of the active derivatives was shown to be involved in regulating the expression of genes associated with peptidoglycan and respiratory metabolisms, as well as virulence factor in bacteria. The enhanced potency and unique mechanism of action of these new pentacyclic triterpenes make them a promising antibacterial agent for further studies.

Differentiation of small alkane and alkyl halide constitutional isomers via encapsulation.

Previously we have demonstrated that host 1 is capable of hydrocarbon gas separation by selective sequestration of butane from a mixture with propane in the headspace above a solution of the host (C. L. D. Gibb, B. C. Gibb, J. Am. Chem. Soc., 2006, 128, 16498-16499). Expanding on the idea of using this host as a means to affect guest discrimination, we report here on NMR studies of the binding of constitutional isomers of two classes of small molecules: hexanes and chloropentanes. Our results indicate that even with these relatively straightforward classes of molecules, guest binding is complicated. Overall, host 1 displays a preference to bind guests with a X-C(R2)-C(R2)-Me (X = Cl or Me) structure, and more generally, a preference for branched guests rather than highly flexible, unbranched derivatives. The complexity of binding of these isomers is magnified when considering molecular differentiation between pairs of guests. In such cases, different guests demonstrated different propensities to self-sort; some self-sort exclusively, while others show very little propensity to do so. However, whereas the pool of guests reveals some general correlations between binding strength and structure, no obvious relationship between structure and degree of self-sorting was observed.

Simple preparation of positively charged silver nanoparticles for detection of anions by surface-enhanced Raman spectroscopy.

Modification of citrate and hydroxylamine reduced Ag colloids with thiocholine bromide, a thiol functionalized quaternary ammonium salt, creates particles where the zeta potential is switched from the normal values of ca.-50 mV to ca. +50 mV. These colloids are stable but can be aggregated with metal salts in much the same way as the parent colloids. They are excellent SERS substrates for detection of anionic targets since their positive zeta potentials promote adsorption of negatively charged ions. This is important because the vast majority of published SERS studies involve cationic or neutral targets. Moreover, the fact that the modifier is a quaternary ammonium ion means that the negative surface charge is maintained even at alkaline pH. The modified colloids can be used to detect compounds which cannot be detected using conventional negatively-charged citrate or hydroxylamine reduced metal nanoparticles, for example the detection limit was 5.0 × 10(-5) M for perchlorate and <8.7 × 10(-7) M for tetraphenylporphine tetrasulfonic acid (TPPS). More importantly, picric acid (an explosive) and diclofenac (a non-steroidal anti-inflammatory) could also be analysed quantitatively at low concentrations, 2.5 × 10(-5) M and 1.9 × 10(-5) M, respectively. Interestingly, the correct choice of aggregating agent is important for achieving high sensitivity since the anion in the aggregating salt may compete with anionic targets for surface binding sites. Finally, since the modification procedure simply involves reaction of nanoparticles with a small alkyl thiol derivative, it can easily be adapted to other particle morphologies or metals.

ChemInform Abstract: The Use of a Mitsunobu Reagent for the Formation of Heterocycles: A Simple Method for the Preparation of 3‐Alkyl‐5‐aryl‐1,3,4‐oxadiazol‐2(3H)‐ones from Carboxylic Acids.

AbstractThe reaction proceeds smoothly when Mitsunobu reagents with smaller alkyl groups are used.

Catalyst activation and the dimerization energy of alkylaluminium compounds

Alkylation of olefin polymerization catalyst precursors with Me3Al (or MAO) is a crucial first step in the activation of many polymerization catalysts. However, structures with alkyls and/or halides bridging between aluminium atoms, are known problem cases for DFT methods. We have explored the scope of the problem and possible solutions. The performance of various DFT methods for a range of bridged dimers [H2M]2(μ-X)2 and [Me2M]2(μ-X)2 (M = Al–Tl, X = H, Me, NMe2, OMe, F, Cl) and related compounds was investigated in a systematic fashion. In the absence of reliable experimental data, highly accurate calculated dimerization and complexation energies (extrapolated to the CCSD(T,Full)/aug-cc-pVQZ level of theory: fully correlated Coupled-Cluster Theory with Single and Double and Perturbative Triple excitations) for 26 model systems relevant to Ziegler–Natta catalysis and related chemistry serve as reference. Most functionals (strongly) underestimate the dimerization energy for both electron-deficient (hydride, alkyl) and regular (halide, alkoxide, amide) bridges, and for both main-group and transition metals. To reach “chemical accuracy”, a basis set of VTZ quality (with BSSE correction) or VQZ (without BSSE correction) is recommended, in combination with the M06-2X functional, or with the TPSSTPSS functional plus Grimme's D2 correction. Subsequently, we explored alkylation of olefin polymerization catalyst precursors LTiX2 (L = bis(cyclopentadienyl), Salan or Salalen) with Me3Al to LTiMe2. Using our recommended procedure, we find that the process is exergonic for most electronegative groups X (F, Cl, OR, NR2) provided the dimerization energies of Me3Al and Me2AlX are taken into account. Moreover, alkylation is more exergonic for metallocenes, which we ascribe to the more saturated nature of the Cp2M fragment. Alkylation is predicted to be more favourable for amides and alkoxides than for the widely used chloride precursors, and failure to exploit those precursors in catalysis is likely due to kinetic issues caused by steric factors. In particular, employing metal alkoxides or amides with small alkyl groups (OMe, OEt) rather than the commonly used bulky OiPr and OtBu groups might yield catalyst precursors that can be activated more easily than chlorides.

What a difference a bond makes: the structural, chemical, and physical properties of methyl-terminated Si(111) surfaces.

The chemical, electronic, and structural properties of surfaces are affected by the chemical termination of the surface. Two-step halogenation/alkylation of silicon provides a scalable, wet-chemical method for grafting molecules onto the silicon surface. Unlike other commonly studied wet-chemical methods of surface modification, such as self-assembly of monolayers on metals or hydrosilylation on silicon, the two-step method enables attachment of small alkyl chains, even methyl groups, to a silicon surface with high surface coverage and homogeneity. The methyl-terminated Si(111) surface, by comparison to hydrogen-terminated Si(111), offers a unique opportunity to study the effects of the first surface bond connecting the overlayer to the surface. This Account describes studies of methyl-terminated Si(111), which have shown that the H-Si(111) and CH3-Si(111) surfaces are structurally nearly identical, yet impart significantly different chemical and electronic properties to the resulting Si surface. The structure of methyl-terminated Si(111) formed by a two-step halogenation/methylation process has been studied by a variety of spectroscopic methods. A covalent Si-C bond is oriented normal to the surface, with the methyl group situated directly atop a surface Si atom. Multiple spectroscopic methods have shown that methyl groups achieve essentially complete coverage of the surface atoms while maintaining the atomically flat, terraced structure of the original H-Si(111) surface. Thus, the H-Si(111) and CH3-Si(111) surface share essentially identical structures aside from the replacement of a Si-H bond with a Si-C bond. Despite their structural similarity, hydrogen and methyl termination exhibit markedly different chemical passivation. Specifically, CH3-Si(111) exhibits significantly greater oxidation resistance than H-Si(111) in air and in aqueous electrolyte under photoanodic current flow. Both surfaces exhibit similar thermal stability in vacuum, and the Si-H and Si-C bond strengths are expected to be very similar, so the results suggest that methyl termination presents a greater kinetic barrier to oxidation of the underlying Si surface. Hydrogen termination of Si(111) provides nearly perfect electronic passivation of surface states (i.e., less than 1 electronic defect per 40 million surface atoms), but this electronic passivation is rapidly degraded by oxidation in air or under electrochemical conditions. In contrast, methyl termination provides excellent electronic passivation that resists degradation due to oxidation. Moreover, alkylation modifies the surface electronic structure by creating a surface dipole that effectively changes the electron affinity of the Si surface, facilitating modification of the charge-transfer kinetics across Si/metal or Si/electrolyte junctions. This Account also briefly describes recent studies of mixed monolayers formed by the halogenation/alkylation of silicon. Mixed monolayers allow attachment of bulkier groups that enable secondary chemistry at the surface (e.g., attachment of molecular catalysts or seeding of atomic layer deposition) to be combined with methyl termination of remaining unreacted surface sites. Thus, secondary chemistry can be enabled while maintaining the chemical and electronic passivation provided by complete termination of surface atoms with Si-C bonds. Such studies of mixed monolayers demonstrate the potential use of a wet-chemical surface modification scheme that combines both chemical and electronic passivation.

Synthesis, leishmanicidal and cytotoxic activity of triclosan-chalcone, triclosan-chromone and triclosan-coumarin hybrids.

Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 7–9 and 17, were active against Leishmania parasites (EC50 = 9.4; 10.2; 13.5 and 27.5 µg/mL, respectively) and showed no toxicity toward mammalian cells (>200 µg/mL). They are potential candidates for antileishmanial drug development. Compounds 25–27, were active and cytotoxic. Further studies using other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo.