Nonactin,monactin, dinactin,trinactin, and tetranactin. A Raman spectroscopic study

Raman spectra are reported for crystalline nonactin, monactin, dinactin, trinactin, and tetranactin and their solutions in CCl₄, CHCl₃, CH₃OH, and 4:1 (v/v) CH₃OH:CHCl₃. The macrotetrolide nactins selectively bind a wide variety of cations, and are important model compounds for the study of ion complexation. The conformations of nonactin, monactin, and dinactin in solution are similar. Their conformations are found to be sufficiently open to permit the ester carbonyl groups to form hydrogen bonds with CH₃OH; this gives rise to characteristic changes in the vibration frequencies associated with the ester groups. Nonactin, which is the least soluble of the nactins in CH₃OH, is also the least effective at forming hydrogen bonds with CH₃OH. The greater ability of the higher nactins to form hydrogen bonds with CH₃OH may be due to the increased inductive effect of ethyl over methyl side chains, which may increase the dipole moment of the ester carbonyl groups. Spectra of crystalline nonactin, monactin, and tetranactin are fairly similar, while the spectra of dinactin and trinactin comprise a second, distinct family. This is consistent with X-ray crystallographic studies, which show that nonactin and tetranactin form monoclinic crystals, while trinactin is triclinic.     

Isostructural unbranched alkyl‐chains as tools for stabilizing β‐turn structure

To investigate the structural role played by isostructural unbranched alkyl‐chains on the conformational ensemble and stability of β‐turn structures, the conformational properties of a designed model peptide: Plm‐Pro‐Gly‐Pda ( 1 , Plm: H₃C—(CH₂)₁₄—CONH—; Pda: —CONH— (CH₂)₁₄—CH₃) have been examined and compared with the parent peptide: Boc‐Pro‐Gly‐NHMe ( 2 , Boc: tert‐butoxycarbonyl; NHMe: N‐methylamide). The characteristic ¹³C NMR chemical‐shifts of the Pro C^β and C^γ resonances ascertained the incidence of an all‐trans peptide‐bond in low polarity deuterochloroform solution. Using FTIR and ¹H NMR spectroscopy, we establish that apolar alkyl‐chains flanking a β‐turn promoting Pro‐Gly sequence impart definite incremental stability to the well‐defined hydrogen‐bonded structure. The assessment of ¹H NMR derived thermodynamic parameters of the hydrogen‐bonded amide‐NHs via variable temperature indicate that much weaker hydrophobic interactions do contribute to the stability of folded reverse turn structures. The far‐UV CD spectral patterns of 1 and 2 in 2,2,2‐trifluoroethanol are consistent with Pro‐Gly specific type II β‐turn structure, concomitantly substantiate that the flanking alkyl‐chains induce substantial bias in enhanced β‐turn populations. In view of structural as well as functional importance of the Pro‐Gly mediated secondary structures, besides biochemical and biological significance of proteins lipidation via myristoylation or palmytoilation, we highlight potential convenience of the unbranched Plm and Pda moieities not only as main‐chain N‐ and C‐terminal protecting groups but also to mimic and stabilize specific isolated secondary and supersecondary structural components frequently observed in proteins and polypeptides. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 419–426, 2013.     

1,1′-Bis(3-hydroxypropyl)ferrocene: Preparation and substitution with polyfluoroalkyl groups

SiMe₃CH₂CH₂ was demonstrated as a robust and convenient OH protecting group in the preparation of 1,1′-bis(3-hydroxypropyl)ferrocene (1). The OH groups were used to introduce polyfluorinated alkyl chains by acylation of 1 with (C₂F₅CO)₂O and alkylation with CF₃(CF₂)₆CH₂OH under Mitsunobu reaction conditions. This demonstrates a new method for introduction of an ω-hydroxyalkyl group to the Cp unit as a synthetic handle for modification of molecular properties.     

Synthesis, immobilization, and solid-state NMR of new phosphine linkers with long alkyl chains

Monodentate and chelating phosphines with long alkyl chains, incorporating ethoxy- or chlorosilane functions for immobilizations, have been synthesized and fully characterized. The new compounds (EtO)₃Si(CH₂)_xPPh₂, Cl₂Si(CH₂CH₂PPh₂)₂, and (EtO)₂Si[(CH₂)_xPPh₂]₂ (x = 7, 11) could be prepared in high yields from cheap starting materials, and they have been characterized by multinuclear NMR spectroscopy and X-ray crystallography. The phosphines have been immobilized on silica in a well-defined manner, and the modified silicas have been studied by ³¹P and ²⁹Si solid-state NMR of the dry materials and of the suspensions.     

Effects of alkyl chain lengths of gallates upon enzymatic wool functionalisation

The covalent grafting of alkyl gallates on wool through a laccase catalysed reaction in 80/20 (v/v, %) aqueous–ethanol mixture provided in a one-step process a multifunctional textile material with antioxidant, antibacterial and water repellent properties. Gallic acid and its alkyl esters ethyl, propyl, octyl and dodecyl gallate have been enzymatically grafted on wool fibres in order to study the effect of alkyl chain length on wool functional modification. The capacity of laccase to oxidise these phenolic compounds in an aqueous–organic medium has been verified by electrochemical techniques. The increase of CH₂, CH₃ groups in the FTIR spectra, together with the XPS analysis of the enzymatically modified fabrics confirmed the covalent grafting of ester gallates on wool. The result obtained in this work for antibacterial, water repellent as well as antioxidant properties show that the length of the alkyl chain of gallates molecule play an important role on wool functionalisation.     

Phenolic esters with potential anticancer activity - the structural variable

The conformational preferences of several potential anticancer dihydroxycinnamic esters with a variable length alkyl chain were studied by quantum-mechanical (DFT) calculations (both for the isolated molecule and for aqueous solutions). The orientation of the hydroxyl ring substituents and of the alkyl ester moiety relative to the carbonyl group showed these to be the most determinant factors for the overall stability of this type of phenolic systems, strongly dependent on an effective π-electron delocalization. Compared to the parent caffeic acid (dihydroxycinnamic acid), esterification was found to lead to a higher conformational freedom, and to affect mainly the energy barrier corresponding to the (O=)C-OR internal rotation. No particular differences were verified to occur upon lengthening of the ester alkyl chain, except when this is branched instead of linear. The vibrational spectra of the whole series of compounds were simulated, based on their calculated harmonic vibrational frequencies, and a preliminary assignment was performed. Figure Schematic representation of the dihydroxycinnamic esters studied in the present work and of the main internal rotations affecting the overall stability of the molecules. (R=(CH₂)_n, n = 0,1,2,3,7,11 for MC, EC, PC, BC, OC and DC, respectively; R=(CHCH₃) for IPC. The atom numbering is included, with the exception of the alkyl ester group)     

Crystal structures and thermal analyses of alkyl 2-deoxy-α-d-arabino-hexopyranosides

The crystal structures of alkyl 2-deoxy-α-d-arabino-hexopyranosides, with the alkyl chain lengths from C₈ to C₁₈, are established by the single crystal X-ray structural determination. The even-alkyl chain length derivatives crystallized orthorhombic, with space group P2₁2₁2₁, whereas the odd-alkyl chain length derivatives crystallized monoclinic, with space group P2₁. The sugar moieties retained a ⁴C₁ chair conformation and the conformation of the alkyl chains was all-trans. The molecules formed a bilayer structure, in which alkyl chains were interdigitated. The hydrogen bonds, originating from the sugar moieties, were observed in adjacent layers and also within the same layer, resulting in the formation of infinite chains. The alkyl chains arranged parallel to each other and formed planar structures. The thermal properties of the alkyl 2-deoxy glucosides were analyzed further. It was observed that none of the derivatives exhibited mesomorphism. This study establishes that the absence of the hydroxyl group at C-2 of the sugar moiety results in a non-mesogenic nature of the alkyl 2-deoxy-α-d-glycosides, as opposed to the profound mesogenic nature of the normal alkyl glycosides.     

Each phospholipase A2 type exhibits distinct selectivity toward sn-1 ester,alkyl ether,and vinyl ether phospholipids

Glycerophospholipids are major components of cell membranes and have enormous variation in the composition of fatty acyl chains esterified on the sn-1 and sn-2 position as well as the polar head groups on the sn-3 position of the glycerol backbone. Phospholipase A₂ (PLA₂) enzymes constitute a superfamily of enzymes which play a critical role in metabolism and signal transduction by hydrolyzing the sn-2 acyl chains of glycerophospholipids. In human cell membranes, in addition to the conventional diester phospholipids, a significant amount is the sn-1 ether-linked phospholipids which play a critical role in numerous biological activities. However, precisely how PLA₂s distinguish the sn-1 acyl chain linkage is not understood. In the present study, we expanded the technique of lipidomics to determine the unique in vitro specificity of three major human PLA₂s, including Group IVA cytosolic cPLA₂, Group VIA calcium-independent iPLA₂, and Group V secreted sPLA₂ toward the linkage at the sn-1 position. Interestingly, cPLA₂ prefers sn-1 vinyl ether phospholipids known as plasmalogens over conventional ester phospholipids and the sn-1 alkyl ether phospholipids. iPLA₂ showed similar activity toward vinyl ether and ester phospholipids at the sn-1 position. Surprisingly, sPLA₂ preferred ester phospholipids over alkyl and vinyl ether phospholipids. By taking advantage of molecular dynamics simulations, we found that Trp30 in the sPLA₂ active site dominates its specificity for diester phospholipids.     

The reactivity of affinity labels: A kinetic study of the reaction of alkyl halides with thiolate anions—a model reaction for protein alkylation

Factors have been investigated which govern the electrophilic reactivity of alkyl halides with thiolate anions in aqueous solution. In the series of alkyl halides studied, some are potential metal-directed affinity labels, while others are frequently used in protein modification. Previous data on the kinetics of this type of alkylation are compared with the present results. The influence of electronic, polar, and steric factors on alkyl halide reactivity is seen. The following order of reactivity for alkyl halides bearing different α substituents was observed: RCH₂CH(X)COOCH₃ > RCH₂CH(X)CONH₂ > RCH₂CH(X)COOH > RCH₂CH₂X > RCH₂CH(X)CH₂OH. The metal-directed affinity labels are imidazole derivatives, some of which have substituents in their imidazole ring. The effect of the imidazole ring and of ring substitution on reactivity is seen. The nucleophilic reactivity of thiols is highly pH dependent since the thiolate anion (RS^?) is the reactive species, but only minor differences emerged between different free thiolates.     

Use of Self-Assembled Monolayers of Different Wettabilities To Study Surface Selection and Primary Adhesion Processes of Green Algal (Enteromorpha) Zoospores

We investigated surface selection and adhesion of motile zoospores of a green, macrofouling alga (Enteromorpha) to self-assembled monolayers (SAMs) having a range of wettabilities. The SAMs were formed from alkyl thiols terminated with methyl (CH₃) or hydroxyl (OH) groups or mixtures of CH₃- and OH-terminated alkyl thiols and were characterized by measuring the advancing contact angles and by X-ray photoelectron spectroscopy. There was a positive correlation between the number of spores that attached to the SAMs and increasing contact angle (hydrophobicity). Moreover, the sizes of the spore groups (adjacent spores touching) were larger on the hydrophobic SAMs. Video microscopy of a patterned arrangement of SAMs showed that more zoospores were engaged in swimming and “searching” above the hydrophobic sectors than above the hydrophilic sectors, suggesting that the cells were able to “sense” that the hydrophobic surfaces were more favorable for settlement. The results are discussed in relation to the attachment of microorganisms to substrata having different wettabilities.     

Mid-infrared spectroscopy is a fast screening method for selecting Arabidopsis genotypes with altered leaf cuticular wax

Arabidopsis eceriferum (cer) mutants with unique alterations in their rosette leaf cuticular wax accumulation and composition established by gas chromatography have been investigated using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy in combination with univariate and multivariate analysis. Objectives of this study were to evaluate the utility of ATR-FTIR for detection of chemical diversity in leaf cuticles, obtain spectral profiles of cer mutants in comparison with the wild type, and identify changes in leaf cuticles caused by drought stress. FTIR spectra revealed both genotype- and treatment-dependent differences in the chemical make-up of Arabidopsis leaf cuticles. Drought stress caused specific changes in the integrated area of the CH₃ peak, asymmetrical and symmetrical CH₂ peaks, ester carbonyl peak and the peak area ratio of ester CO to CH₂ asymmetrical vibration. CH₃ peak positively correlated with the total wax accumulation. Thus, ATR-FTIR spectroscopy is a valuable tool that can advance our understanding of the role of cuticle chemistry in plant response to drought and allow selection of superior drought-tolerant varieties from large genetic resources.     

Plant Growth Inhibition and Membrane Penetration by a Homologous Series of Dichlorobenzoate Esters

The homologous series of n-alkyl esters (C₁–C₁₀) of 3,4-dichlorobenzoic acid was synthesized and their effects in inhibiting the growth of Nicotiana meristems were studied. The inhibition of growth was considered in terms of penetration of chemicals into the plant tissue and subsequent cell membrane disruption. Penetration was investigated by applying the emulsified ester to the meristem and then measuring the compound recovered with the isolated surface lipids. Decreasing amounts of 3,4-dichlorobenzoate esters penetrated into the plant as the alkyl chain length of the ester moeity was increased. Essentially no penetration occurred with the n-C₇ through C₁₀ esters tested. The effect of the ester homologues on cell membranes was studied by measuring the efflux of betacyanin from beet root cells. Decreasing amounts of pigments were released as the alkyl chain length of the ester was increased. Minimal cell membrane disruption was found for the C₇–C₁₀ esters. Inhibition of the plant meristem may result from the more rapid penetration of the short chain ester homologues into the plant.     

Phase behaviour and crystallinity of plant cuticular waxes studied by Fourier transform infrared spectroscopy

The phase behaviour of cuticular waxes from leaves of Hedera helix L. and Juglans regia L. was studied by Fourier transform infrared spectroscopy. For this purpose reconstituted waxes, isolated cuticular membranes, dewaxed polymer matrix membranes and whole leaves were studied in the horizontal attenuated total reflection and transmission modes. Melting curves of cuticular waxes were derived from temperature-dependent changes in the absorption maximum of the symmetric stretching mode of CH₂ groups (ν_s, at approx. 2856–2848 cm⁻¹). With increasing temperature absorption band doublets due to CH₂ scissoring (δ_sciss) and rocking (δ_rock) movements (at approx. 1473–1471 and 730–720 cm⁻¹, respectively) indicative of an orthorhombic arrangement of alkyl chains merged into a single peak. The area ratio of the peaks at approx. 720 and 730 cm⁻¹ was used as a measure for aliphatic crystallinity of plant cuticular waxes at a given temperature. The investigations of reconstituted cuticular waxes and those still embedded in isolated cuticles or in situ on the leaf produced comparable results. The findings are discussed in terms of the properties of the cuticular transport barrier. Received: 21 March 1997 / Accepted: 25 April 1997     

Synthesis and size regulation of gold nanoparticles by controlled thermolysis of ammonium gold(I) thiolate in the absence or presence of amines

Controlled thermolysis of gold(I) complex with no use of solvent was investigated as a novel synthetic method of gold nanoparticles. A series of precursors, ammonium gold(I) thiolate [RN(CH₃)₃][Au(SC₁₂H₂₅)₂] (R = C₈H₁₇, C₁₂H₂₅, and C₁₄H₂₉) and [(C₁₈H₃₇)₂N(CH₃)₂][Au(SC₁₂H₂₅)₂], have been prepared and the thermolysis of those precursors was conducted at 180 °C for 5 h under an N₂ atmosphere, providing spherical gold nanoparticles stabilized by alkyl groups derived from the precursor, gold(I) complex. In spite of thermolysis process, the average diameter of gold nanoparticles deriving from [C₁₂H₂₅N(CH₃)₃][Au(SC₁₂H₂₅)₂] was 22 nm, but the size distribution ranges from 11 to 76 nm. For the purpose of the size regulation of the gold nanoparticles, equimolar primary, secondary, or tertiary alkylamines are added as stabilizer and mild reductant to the controlled thermolysis of gold(I) complex at lower temperature of 165 °C for 5 h. The gold nanoparticles obtained by the controlled thermolysis in the presence of stearylamine are well regulated and almost monodispersed nanoparticles with average diameter of 7.5 nm. Such size regulation resulted from the inhibition of the growth of gold nuclei by transforming reaction from ammonium and thiolate moieties to neutral tertiary amine, thiol and sulfide, which function as stabilizer for gold nanoparticles.     

Hydrocarbon-coated sepharoses. Use in the purification of glycogen phosphorylase

A homologous series of hydrocarbon-coated Sepharoses varying in the length of their alkyl side chains (Seph-NH(CH₂)_nH) was synthesized. These modified Sepharoses provide a versatile tool for the purification of proteins, since, by choosing the suitable member of the series, a desired protein can be extracted from a protein mixture. This is illustrated in the case of glycogen phosphorylase, which is not retained at all by methyl Sepharose (n=1), is retarded by propyl Sepharose (n=3), is adsorbed on butyl Sepharose (n=4) and can be eluted from the column by deforming buffers, and is so tightly adsorbed on hexyl Sepharose (n=6) that it could be eluted from the column only in the denatured form, by washing with 0.2 N CH₃COOH. On a preparative scale, a hundred-fold purification of phosphorylase could be achieved in one step, by passage of a crude muscle extract on a small butyl Sepharose column.     

Electrostatically induced change of the conformational order of charged lipid membranes

Raman spectroscopy and X-ray diffraction are used to investigate the influence of surface charges on the structure of ionizable lipid membranes of dimyristoylmethylphosphatidic acid. The membrane surface charge density is regulated by varying the pH of the aqueous phase. Changes of the conformational order of the lipid chains are determined from the intensity of the CC stretch chain vibrations around 1100 cm^?1 in a lipid Raman spectrum. In going from an electrical neutral to a negatively charged membrane, the conformational order is reduced by 5% in the ordered and by 9% in the fluid membrane phase, corresponding to 0.6 and 0.8 CC bonds, respectively, which change from a trans to a gauche conformation. The electrostatically induced conformational change is mainly concentrated at the lipid chain ends as indicated by the spectral variations of the 890 cm^?1 CH₃ rocking band of the chain termini. The X-ray diffraction experiments show that increasing the surface charge density in the ordered membrane phase leads to a lateral expansion of the packing of the lipid polar groups, whereas the packing of the lipid chains in a plane perpendicular to the chain axes remains constant, indicating an increase of the tilt of the lipid chains from δ = 10° (pH 3) to δ = 27° (pH 9).     

Functional nickel thiosalen complexes: structure and solid-state packing of a transition metal-based surfactant

The complex NiBr₂(2-C₁₂H₂₅SC₆H₄CHNCH₂CH₂NCHC₆H₄SC₁₂H₂₅-2) (1) was prepared from the ligand 2-C₁₂H₂₅SC₆H₄CHNCH₂CH₂NCHC₆H₄SC₁₂H₂₅-2 (3) and NiBr₂. Paramagnetic 1 was characterized by combustion analyses, ¹H and ¹³C NMR spectroscopy, Vis–NIR spectroscopy, measurement of its magnetic susceptibility, and single-crystal X-ray diffraction. The crystal structure of 1 features octahedral coordination of Ni(II) with axial bromides and fully extended interdigitated alkyl chains. There are significant differences between the solid state structures of 1 and NiBr₂(2-C₆H₁₂SC₆H₄CHNCH₂CH₂NCHC₆H₄SC₆H₁₂-2) (2), a previously reported homologue.     

Structural Basis for the Binding Affinity of a Homologous Series of Synthetic Phenoxazone Drugs with DNA: NMR and Molecular Mechanics Analysis

Abstract

The molecular basis of the marked structure-activity relationship for a homologous series of DNA-binding phenoxazone drugs (ActII-ActIV) has been investigated by NMR spectroscopy and molecular mechanics. The spatial structures of the complexes between the drugs and a model deoxytetranucleotide, 5′-d(TpGpCpA), have been determined by molecular mechanics methods using homonuclear ¹H-¹H 2D-NOESY and heteronuclear ¹H-³¹P (HMBC) NMR spectroscopic data. Observed intermolecular NOE contacts and equilibrium binding studies confirm that the binding affinity of the synthetic phenoxazone derivatives with d(TGCA) decreases with an increase in the number of CH₂ groups in the dimethylami- noalkyl side chains, i.e., ActII > ActIII > ActIV, in agreement with the observed biological activity of these compounds. Molecular mechanics calculations of the spatial structures of the intercalated complexes of ActII-ActIV with d(TGCA) indicate that the different binding constants of the phenoxazone derivatives with the DNA oligomer are due to the different degrees of intercalation of the chromophore and the different steric arrangements of aminoalkyl side chains in the minor groove of the tetramer duplex; this results in different distances between the negatively-charged phosphates of the DNA duplex and the terminal positively-charged N(CH₃)₂ groups of the side chains.     

A polyethylene-glycol-functionalized ring-like isopolymolybdate cluster

A new organic-inorganic hybrid compound, Na₆[HO(CH₂CH₂O)₄H]₃{Mo₃₆O₁₀₈(H₂O)₁₄(OH)₆[HO(CH₂CH₂O)₃H]₂} · ∼75H₂O (1) has been obtained in polyethylene glycol (PEG)/H₂O system with a good yield, and characterized by element analysis, IR, UV, TG, ¹³C NMR spectroscopy, electrochemistry and X-ray single crystal diffraction analysis. Compound 1 consists of the {Mo₃₆} clusters as the structural motif covalently decorated by PEG fragments. Such hybrid polyoxoanions are linked by Na⁺ counter-cations, leading to one-dimensional chains. The adjacent chains are closely packed together into a three-dimensional supramolecular framework via extensive H-bonding interactions among polyoxoanions and the isolated water molecules.     

Interaction of alkyl ammonium derivatives with red cells: Hemolysis and sodium pump inhibition studies

Summary Members of four homologous series of tetra-alkyl ammonium bromides (R ₃N⁺(CH₂) _n–1·CH₃Br^– whereR=H, CH₃ or C₂H₅ andRN⁺H₃Br^– whereR represents the isomeric butyl series) have been synthesized and tested as sodium pump inhibitors, measured as ouabain-sensitive K⁺ influx, and as hemolytic agents on human red cells.Potency for both effects is presented graphically, plotting the logarithm of the concentration for half maximal effect against alkyl chain length. Both hemolysis and pump inhibition studies yielded a biphasic response consisting of two good straight lines, with effectiveness increasing up to C10–12 and then remaining constant up to C20.For hemolysis the alkyl ammonium series was most effective. The calculated free-energy change per methylene group was the same for three series of compounds, but the free-energy contribution from the headgroup was lower for the ammonium series.In contrast, although pump inhibition studies also yielded simple biphasic plots, inhibition occurred at 3- to 50-fold lower concentrations and there were significant differences between the three series, both in the free-energy changes per methylene group and in the headgroup contributions.We have analyzed these results thermodynamically to take account of hydrophobic interactions and the conformation of the alkyl chains.