RESUMO
Synthetic iron-sulfur cubanes are models for biological cofactors, which are essential to delineate oxidation states in the more complex enzymatic systems. However, a complete series of [Fe4S4]n complexes spanning all redox states accessible by 1-electron transformations of the individual iron atoms (n = 0-4+) has never been prepared, deterring the methodical comparison of structure and spectroscopic signature. Here, we demonstrate that the use of a bulky arylthiolate ligand promoting the encapsulation of alkali-metal cations in the vicinity of the cubane enables the synthesis of such a series. Characterization by EPR, 57Fe Mössbauer spectroscopy, UV-visible electronic absorption, variable-temperature X-ray diffraction analysis, and cyclic voltammetry reveals key trends for the geometry of the Fe4S4 core as well as for the Mössbauer isomer shift, which both correlate systematically with oxidation state. Furthermore, we confirm the S = 4 electronic ground state of the most reduced member of the series, [Fe4S4]0, and provide electrochemical evidence that it is accessible within 0.82 V from the [Fe4S4]2+ state, highlighting its relevance as a mimic of the nitrogenase iron protein cluster.
Assuntos
Materiais Biomiméticos , Coenzimas , Hidrocarbonetos , Ferro , Nitrogenase , Enxofre , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Coenzimas/síntese química , Coenzimas/química , Hidrocarbonetos/síntese química , Hidrocarbonetos/química , Ferro/química , Nitrogenase/química , Oxirredução , Enxofre/químicaRESUMO
An iron-catalyzed C-H functionalization of simple monosubstituted allenes is reported. An efficient protocol for this process was made possible by the use of a newly developed electron-rich and sterically hindered cationic cyclopentadienyliron dicarbonyl complex as the catalyst and N-sulfonyl hemiaminal ether reagents as precursors to iminium ion electrophiles. Under optimized conditions, the use of a mild, functional-group-tolerant base enabled the conversion of a range of monoalkyl allenes to their allenylic sulfonamido 1,1-disubstituted derivatives, a previously unreported and contrasteric regiochemical outcome for the C-H functionalization of electronically unbiased and directing-group-free allenes.
Assuntos
Alcadienos/síntese química , Hidrocarbonetos/síntese química , Ferro/química , Alcadienos/química , Catálise , Hidrocarbonetos/química , Ligação de Hidrogênio , Modelos Moleculares , Estrutura MolecularRESUMO
A DNA-encoded chemical library (DECL) is built with combinatorial chemistry, which works by bringing chemical fragments together to generate diverse structures. However, chemical diversity of DNA-encoded chemical libraries is often limited by DNA compatible synthetic reactions. This report shows a conceptual strategy to expand chemical space of DNA-encoded chemical libraries by incorporation of diversity-oriented synthesis in DECL synthesis. We developed Aldol reactions on DNA in a combinatorial way. After obtaining DNA-tagged α, ß-unsaturated ketones which represent important chemical intermediates, many distinct structures with skeletal diversities are achieved by diversity-oriented synthesis.
Assuntos
Técnicas de Química Combinatória , DNA/química , Hidrocarbonetos/síntese química , Bibliotecas de Moléculas Pequenas , Descoberta de Drogas , Hidrocarbonetos/química , Estrutura Molecular , Conformação de Ácido Nucleico , Especificidade por SubstratoRESUMO
A nickel-catalyzed regiodivergent hydroarylation and hydroalkenylation of unactivated alkenyl carboxylic acids is reported, whereby the ligand environment around the metal center dictates the regiochemical outcome. Markovnikov hydrofunctionalization products are obtained under mild ligand-free conditions, with up to 99 % yield and >20:1 selectivity. Alternatively, anti-Markovnikov products can be accessed with a novel 4,4-disubstituted Pyrox ligand in excellent yield and >20:1 selectivity. Both electronic and steric effects on the ligand contribute to the high yield and selectivity. Mechanistic studies suggest a change in the turnover-limiting and selectivity-determining step induced by the optimal ligand. DFT calculations reveal that in the anti-Markovnikov pathway, repulsion between the ligand and the alkyl group is minimized (by virtue of it being 1° versus 2°) in the rate- and regioselectivity-determining transmetalation transition state.
Assuntos
Alcenos/química , Ácidos Carboxílicos/química , Hidrocarbonetos/síntese química , Níquel/química , Catálise , Teoria da Densidade Funcional , Hidrocarbonetos/química , Ligantes , Estrutura Molecular , EstereoisomerismoRESUMO
Halloysite aluminosilicate nanotubes loaded with ruthenium particles were used as reactors for Fischer-Tropsch synthesis. To load ruthenium inside clay, selective modification of the external surface with ethylenediaminetetraacetic acid, urea, or acetone azine was performed. Reduction of materials in a flow of hydrogen at 400 °C resulted in catalysts loaded with 2 wt.% of 3.5 nm Ru particles, densely packed inside the tubes. Catalysts were characterized by N2-adsorption, temperature-programmed desorption of ammonia, transmission electron microscopy, X-ray fluorescence, and X-ray diffraction analysis. We concluded that the total acidity and specific morphology of reactors were the major factors influencing activity and selectivity toward CH4, C2-4, and C5+ hydrocarbons in the Fischer-Tropsch process. Use of ethylenediaminetetraacetic acid for ruthenium binding gave a methanation catalyst with ca. 50% selectivity to methane and C2-4. Urea-modified halloysite resulted in the Ru-nanoreactors with high selectivity to valuable C5+ hydrocarbons containing few olefins and a high number of heavy fractions (α = 0.87). Modification with acetone azine gave the slightly higher CO conversion rate close to 19% and highest selectivity in C5+ products. Using a halloysite tube with a 10-20-nm lumen decreased the diffusion limitation and helped to produce high-molecular-weight hydrocarbons. The extremely small C2-C4 fraction obtained from the urea- and azine-modified sample was not reachable for non-templated Ru-nanoparticles. Dense packing of Ru nanoparticles increased the contact time of olefins and their reabsorption, producing higher amounts of C5+ hydrocarbons. Loading of Ru inside the nanoclay increased the particle stability and prevented their aggregation under reaction conditions.
Assuntos
Silicatos de Alumínio/química , Monóxido de Carbono/química , Hidrocarbonetos/síntese química , Nanopartículas Metálicas/química , Rutênio/química , Catálise , Argila/química , Ácido Edético/químicaRESUMO
Synergistic palladium and enamine catalysis was explored to promote ketone addition to unactivated olefins. A secondary amine-based organocatalyst was identified as the optimal co-catalyst for the directed Pd-catalyzed alkene activation. Furthermore, asymmetric hydrocarbon functionalization of unactivated alkenes was also achieved with good to excellent yield (up to 96% yields) and stereoselectivity (up to 96% ee). This strategy presented an efficient approach to prepare α-branched ketone derivatives under mild conditions.
Assuntos
Alcenos/química , Hidrocarbonetos/química , Cetonas/química , Paládio/química , Alcenos/síntese química , Aminas/química , Catálise , Hidrocarbonetos/síntese química , Cetonas/síntese química , EstereoisomerismoRESUMO
Abnormal protein-protein interactions (PPIs) are the basis of multiple diseases, and the large and shallow PPI interfaces make the target "undruggable" for traditional small molecules. Peptides, emerging as a new therapeutic modality, can efficiently mimic PPIs with their large scaffolds. Natural peptides are flexible and usually have poor serum stability and cell permeability, features that limit their further biological applications. To satisfy the clinical application of peptide inhibitors, many strategies have been developed to constrain peptides in their bioactive conformation. In this report, we describe several classic methods used to constrain peptides into a fixed secondary structure which could significantly improve their biophysical properties.
Assuntos
Peptídeos/química , Amidas/química , Fenômenos Biofísicos , Dicroísmo Circular , Cristalografia por Raios X , Hidrocarbonetos/síntese química , Hidrocarbonetos/química , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Peptídeos/síntese química , Conformação Proteica em alfa-Hélice , Estabilidade Proteica , Estrutura Secundária de Proteína , Técnicas de Síntese em Fase Sólida , Reagentes de Sulfidrila/químicaRESUMO
FeS proteins are metalloproteins prevalent in the metabolic pathways of most organisms, playing key roles in a wide range of essential cellular processes. A member of this protein family, the Fe protein of nitrogenase, is a homodimer that contains a redox-active [Fe4S4] cluster at the subunit interface and an ATP-binding site within each subunit. During catalysis, the Fe protein serves as the obligate electron donor for its catalytic partner, transferring electrons concomitant with ATP hydrolysis to the cofactor site of the catalytic component to enable substrate reduction. The effectiveness of Fe protein in electron transfer is reflected by the unique reactivity of nitrogenase toward small-molecule substrates. Most notably, nitrogenase is capable of catalyzing the ambient reduction of N2 and CO into NH4+ and hydrocarbons, respectively, in reactions that parallel the important industrial Haber-Bosch and Fischer-Tropsch processes. Other than participating in nitrogenase catalysis, the Fe protein also functions as an essential factor in nitrogenase assembly, which again highlights its capacity as an effective, ATP-dependent electron donor. Recently, the Fe protein of a soil bacterium, Azotobacter vinelandii, was shown to act as a reductase on its own and catalyze the ambient conversion of CO2 to CO at its [Fe4S4] cluster either under in vitro conditions when a strong reductant is supplied or under in vivo conditions through the action of an unknown electron donor(s) in the cell. Subsequently, the Fe protein of a mesophilic methanogenic organism, Methanosarcina acetivorans, was shown to catalyze the in vitro reduction of CO2 and CO into hydrocarbons under ambient conditions, illustrating an impact of protein scaffold on the redox properties of the [Fe4S4] cluster and the reactivity of the cluster toward C1 substrates. This reactivity was further traced to the [Fe4S4] cluster itself, as a synthetic [Fe4S4] compound was shown to catalyze the reduction of CO2 and CO to hydrocarbons in solutions in the presence of a strong reductant. Together, these observations pointed to an inherent ability of the [Fe4S4] clusters and, possibly, the FeS clusters in general to catalyze C1-substrate reduction. Theoretical calculations have led to the proposal of a plausible reaction pathway that involves the formation of hydrocarbons via aldehyde-like intermediates, providing an important framework for further mechanistic investigations of FeS-based activation and reduction of C1 substrates. In this Account, we summarize the recent work leading to the discovery of C1-substrate reduction by protein-bound and free [Fe4S4] clusters as well as the current mechanistic understanding of this FeS-based reactivity. In addition, we briefly discuss the evolutionary implications of this discovery and potential applications that could be developed to enable FeS-based strategies for the ambient recycling of unwanted C1 waste into useful chemical commodities.
Assuntos
Proteínas Ferro-Enxofre/química , Oxirredutases/química , Azotobacter vinelandii/enzimologia , Dióxido de Carbono/química , Monóxido de Carbono/química , Evolução Molecular , Hidrocarbonetos/síntese química , Methanosarcina/enzimologia , Modelos Químicos , OxirreduçãoRESUMO
Lignin, an underutilized source of biomass, is a challenging target for decomposition by both biological and nonbiological approaches. As lignin accounts for 15-40% of the dry weight of lignocellulose, its conversion to valued chemicals is considered promising. Although depolymerization of the complicated lignin structures is still not fully understood, biochemical reactions for various lignin-derived compounds, especially dimeric and monomeric aromatics, have been characterized in some fungi and bacteria known as natural lignin degraders. Synthetic biology, as a useful tool for exploring and engineering biosystems, could be used for protein design and constructing biosynthetic pathways for lignin utilization and upgrading. Understanding mechanisms of ligninolysis will facilitate synthetic biology implementation. In this Perspective, fungal and bacterial biochemical mechanisms for breaking lignin linkages, degrading monomers, and cleaving aromatic rings are examined, whereas enabling valued chemical biosynthesis from lignin-derived compounds via synthetic biology approaches is emphasized. On the basis of the advances in enzyme discovery and metabolic reconstruction, we propose a bottom-up approach to developing microbial platforms for producing valued chemicals from lignin sources.
Assuntos
Lignina/biossíntese , Lignina/química , Biologia Sintética/métodos , Bactérias/metabolismo , Biomassa , Biopolímeros/química , Fungos/metabolismo , Hidrocarbonetos/síntese química , Lignina/metabolismo , Polimerização , ProteóliseRESUMO
A simple approach to synthesize extremely high glass transition temperature (Tg > 300 °C) hydrocarbon polymers that introduces bridged cyclic backbone and bulky pendant group simultaneously is reported. This method uses highly 3,4-regulated poly(phenyl-1,3-butadiene) as a prepolymer for cationic cyclization postmodification. The Tg of cyclized highly 3,4-regulated (94.0%) poly(1-phenyl-1,3-butadiene) (P(1-PB)) can reach 304 °C. To further restrict the movement of bridged cyclic backbone by changing the position of the pendant substituent group, highly 3,4-regulated (96.2%) poly(2-phenyl-1,3-butadiene) (P(2-PB)) is used as the prepolymer. The Tg of its cyclized product reaches 325 °C, and this value is the highest ever reported among all hydrocarbon polymers. The results indicate that the regularity of poly(phenyl-1,3-butadiene) and the pendant substituent group are crucial factors when synthesizing high-temperature hydrocarbon polymers through this approach.
Assuntos
Butadienos/síntese química , Hidrocarbonetos/síntese química , Polímeros/síntese química , Butadienos/química , Cátions , Ciclização , Hidrocarbonetos/química , Polímeros/química , Temperatura de TransiçãoRESUMO
Reported herein is the single-step construction of an anti-configured deoxypropionate motif by syndiospecific propylene oligomerization catalyzed by a Cs -symmetric zirconocene complex. After oligomerization, oxidation of the oligomers by oxygen afforded oligopropylene alcohols in a single step. This strategy was applied to the single-step preparation of rel-(2R,4S,6R,8S)-2,4,6,8-tetramethylundecan-1-ol, the racemic mixture of the synthetic fragment of the cuticular hydrocarbons isolated from the cane beetle Antitrogus parvulus.
Assuntos
Alcenos/química , Besouros/química , Hidrocarbonetos/síntese química , Propionatos/química , Alcenos/síntese química , Animais , Césio/química , Hidrocarbonetos/química , Compostos Organometálicos/química , Oxirredução , Propionatos/síntese química , Estereoisomerismo , Zinco/química , Zircônio/químicaRESUMO
Cu is a unique catalyst for CO2 electroreduction, since it can catalyze CO2 reduction to a series of hydrocarbons, alcohols, and carboxylic acids. Nevertheless, such Cu catalysts suffer from poor selectivity. High pressure of CO2 is considered to facilitate the activity and selectivity of CO2 reduction. Herein, a new strategy is presented for CO2 reduction with improved C2 H4 selectivity on a Cu catalyst by using CO2 capture materials as the support at ambient pressure. N-doped carbon (Nx C) was synthesized through high-temperature carbonization of melamine and l-lysine. We observed that the CO2 uptake capacity of Nx C depends on both the microporous area and the content of pyridinic N species, which can be controlled by the carbonization temperature (600-800 °C). The as-prepared CuO/Nx C catalysts exhibit a considerably higher C2 H4 faradaic efficiency (36 %) than CuO supported on XC-72 carbon black (19 %), or unsupported CuO (20 %). Moreover, there is a good linear relationship between the C2 H4 faradaic efficiency and CO2 uptake capacity of the supports for CuO. The local high CO2 concentration near Cu catalysts, created by CO2 capture materials, was proposed to increase the coverage of CO intermediate, which is favorable for the coupling of two CO units in the formation of C2 H4 . This study demonstrates that pairing Cu catalysts with CO2 capture supports is a promising approach for designing highly effective CO2 reduction electrocatalysts.
Assuntos
Dióxido de Carbono/química , Cobre/química , Técnicas Eletroquímicas/métodos , Álcoois/síntese química , Ácidos Carboxílicos/síntese química , Catálise , Etilenos/química , Hidrocarbonetos/síntese química , Oxirredução , TemperaturaRESUMO
Gas-to-liquid (GTL) products are synthetic hydrocarbons produced from natural gas using a catalytic process known as the Fischer-Tropsch process. This process yields a synthetic crude oil that consists of saturated hydrocarbons which can subsequently be refined to a range of products analogous to those obtained from petroleum refining. However, in contrast to their petroleum-derived analogs, GTL products are essentially free of unsaturated or aromatic compounds and do not contain any sulfur-, oxygen-, or nitrogen-containing compounds. Under new chemical substance notification requirements, an extensive testing program covering the entire portfolio of GTL products has been undertaken to assess their hazardous properties to human health and environment. The results of these studies have been summarized in a two-part review. Part 1 provides an overview of the mammalian toxicity hazardous properties of the various GTL products. This second part of the review focuses on the aquatic, sediment, terrestrial, and avian toxicity studies which assess the ecotoxicological hazard profile of the GTL products. Many challenges were encountered during these tests relating to dosing, analysis and interpretation of results. These are discussed with the intent to share experiences to help inform and shape future regulatory mandates for testing of poorly soluble complex substances. As was the case with the mammalian toxicology review, there were a few cases where adverse effects were found, but overall the GTL products were found to exert minimal adverse ecotoxicological effects and these were less severe than effects observed with their conventional, petroleum-derived analogs.
Assuntos
Ecotoxicologia/métodos , Poluentes Ambientais/toxicidade , Hidrocarbonetos/toxicidade , Gás Natural , Animais , Poluentes Ambientais/síntese química , Poluentes Ambientais/química , Humanos , Hidrocarbonetos/síntese química , Hidrocarbonetos/química , Testes de ToxicidadeRESUMO
Super Lewis acids containing the triflate anion [e.g., Hf(OTf)4 , Ln(OTf)3 , In(OTf)3 , Al(OTf)3 ] and noble metal catalysts (e.g., Ru/C, Ru/Al2 O3 ) formed efficient catalytic systems to generate saturated hydrocarbons from lignin in high yields. In such catalytic systems, the metal triflates mediated rapid ether bond cleavage through selective bonding to etheric oxygens while the noble metal catalyzed subsequent hydrodeoxygenation (HDO) reactions. Near theoretical yields of hydrocarbons were produced from lignin model compounds by the combined catalysis of Hf(OTf)4 and ruthenium-based catalysts. When a technical lignin derived from a pilot-scale biorefinery was used, more than 30â wt % of the hydrocarbons produced with this catalytic system were cyclohexane and alkylcyclohexanes in the jet fuel range. Super Lewis acids are postulated to strongly interact with lignin substrates by protonating hydroxyl groups and ether linkages, forming intermediate species that enhance hydrogenation catalysis by supported noble metal catalysts. Meanwhile, the hydrogenation of aromatic rings by the noble metal catalysts can promote deoxygenation reactions catalyzed by super Lewis acids.
Assuntos
Hidrocarbonetos/síntese química , Ácidos de Lewis/química , Lignina/química , Metais/química , Catálise , Cromatografia Gasosa-Espectrometria de Massas , Mesilatos/química , Rutênio/químicaRESUMO
Due to declining hydrocarbon resources and strengthening environmental regulations, significant attention is directed toward sustainable and nontoxic supplies for the development of green technologies in a variety of industries. This account provides an overview on the sources and recent applications of such materials surveying the most common nontoxic and renewable resources that can be obtained from biological sources. Developing a broad array of technologies based on these materials would establish a truly sustainable green chemical industry. The study thematically discusses various compound groups, eg, carbohydrates, proteins, and triglycerides (oils). Since often the monomers or building blocks of these biopolymers are of significant importance and produced in large amounts, the applications of these compounds are also reviewed.
Assuntos
Biopolímeros/química , Química Verde/métodos , Hidrocarbonetos/química , Hidrocarbonetos/síntese química , Biopolímeros/toxicidade , Hidrocarbonetos/toxicidadeRESUMO
The reduction of CO2 into useful products, including hydrocarbon fuels, is an ongoing area of particular interest due to efforts to mitigate buildup of this greenhouse gas. While the industrial Fischer-Tropsch process can facilitate the hydrogenation of CO2 with H2 to form short-chain hydrocarbon products under high temperatures and pressures, a desire to perform these reactions under ambient conditions has inspired the use of biological approaches. Particularly, enzymes offer insight into how to activate and reduce CO2 , but only one enzyme, nitrogenase, can perform the multielectron, multiproton reduction of CO2 into hydrocarbons. The vanadium-containing variant, V-nitrogenase, displays especial reactivity towards the hydrogenation of CO and CO2 . This Focus Review discusses recent progress towards the activation and reduction of CO2 with three primary V-nitrogenase systems. These systems span both ATP-dependent and ATP-independent processes and utilize approaches with whole cells, isolated proteins, and extracted cofactors.
Assuntos
Dióxido de Carbono/metabolismo , Nitrogenase/metabolismo , Dióxido de Carbono/química , Monóxido de Carbono/química , Hidrocarbonetos/síntese química , Modelos BiológicosRESUMO
Monoterpenes (C10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP production but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes. Biotechnol. Bioeng. 2017;114: 1703-1712. © 2017 Wiley Periodicals, Inc.
Assuntos
Difosfatos/metabolismo , Diterpenos/metabolismo , Proteínas de Escherichia coli/genética , Escherichia coli/fisiologia , Melhoramento Genético/métodos , Geraniltranstransferase/genética , Hidrocarbonetos/síntese química , Monoterpenos/metabolismo , Fosfatos de Poli-Isoprenil/metabolismo , Sesquiterpenos/metabolismo , Monoterpenos/química , Mutação/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Road distress results in high maintenance costs. However, increased understandings of asphalt behaviour and properties coupled with technological developments have allowed paving technologists to examine the benefits of introducing additives and modifiers. As a result, polymers have become extremely popular as modifiers to improve the performance of the asphalt mix. This study investigates the performance characteristics of epoxidized natural rubber (ENR)-modified hot-mix asphalt. Tests were conducted using ENR-asphalt mixes prepared using the wet process. Mechanical testing on the ENR-asphalt mixes showed that the resilient modulus of the mixes was greatly affected by testing temperature and frequency. On the other hand, although rutting performance decreased at high temperatures because of the increased elasticity of the ENR-asphalt mixes, fatigue performance improved at intermediate temperatures as compared to the base mix. However, durability tests indicated that the ENR-asphalt mixes were slightly susceptible to the presence of moisture. In conclusion, the performance of asphalt pavement can be enhanced by incorporating ENR as a modifier to counter major road distress.
Assuntos
Materiais de Construção/análise , Compostos de Epóxi/química , Hidrocarbonetos/química , Borracha/química , Módulo de Elasticidade , Engenharia/métodos , Compostos de Epóxi/síntese química , Temperatura Alta , Hidrocarbonetos/síntese química , Teste de Materiais , Polímeros/síntese química , Polímeros/química , Resistência à TraçãoAssuntos
Produtos Biológicos/farmacologia , Química Farmacêutica , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/farmacologia , Hidrocarbonetos/síntese química , Hidrocarbonetos/farmacologia , Produtos Biológicos/química , Desenho Assistido por Computador , Descoberta de Drogas , Compostos Heterocíclicos/química , Hidrocarbonetos/químicaRESUMO
Antimicrobial peptides (AMPs) occur widely in nature and have been studied for their therapeutic potential. AMPs are of interest due to the large number of possible chemical structural combinations using natural and unnatural amino acids, with varying effects on their biological activities. Using physicochemical properties from known naturally occurring amphipathic cationic AMPs, several hydrocarbon-stapled lipopeptides (HSLPs) were designed, synthesized, and tested for antimicrobial properties. Peptides were chemically modified by N-terminal acylation, C-terminal amidation, and some were hydrocarbon stapled by intramolecular olefin metathesis. The effects of peptide length, amphipathic character, and stapling on antimicrobial activity were tested against Escherichia coli, three species of Gram-positive bacteria (Staphylococcus aureus, Bacillus megaterium, and Enterococcus faecalis), and two strains of Candida albicans. Peptides were shown to disrupt liposomes of different phospholipid composition, as measured by leakage of a fluorescent compound from vesicles. Peptides with (S)-2-(4'-pentenyl)-alanine substituted for l-alanine in a reference peptide showed a marked increase in antimicrobial activity, hemolysis, and membrane disruption. Stapled peptides exhibited slightly higher antimicrobial potency; those with greatest hydrophobic character showed the greatest hemolysis and liposome leakage, but lower antimicrobial activity. The results support a model of HSLPs as membrane-disruptive AMPs with potent antimicrobial activity and relatively low hemolytic potential at biologically active peptide concentrations.