The effect of cholesterol on glycerophosphono- and glycerophosphinocholines. Permeability measurements in lipid vesicles

The kinetics of spontaneous chloride ion efflux and valinomycin-mediated rubidium-86 efflux from vesicles prepared from synthetic phospholipids with carbon-phosphorus linkages were investigated at temperatures above the gel-to-liquid-crystalline phase transition. The rate constants for the movement of chloride and rubidium ions were reduced by incorporation of cholesterol into bilayers of phosphono- and phosphinocholines. Nonisosteric phosphonolipids in which the oxygen was removed from the glycerol side of phosphorus without substitution by a methylene group interacted less with cholesterol than the analogous isosteric derivatives, as judged from the magnitude of the decrease in the rate constants for chloride and rubidium ion efflux. The experiments reported in this study suggest that steric factors in the glycerol side of the phosphorus function are important in phosphatidylcholine-cholesterol interaction. However, the oxygen atom on the choline side of the phosphorus in the phosphatidylcholine molecule is not required for strong phosphatidylcholine-cholesterol interaction, since isosteric glycerophosphinocholines interacted as well as the corresponding isosteric glycerophosphonocholines. Furthermore, steric requirements on the choline side of phosphorus are not important in this interaction since phosphinates whose head-group structures are -P(O⁻)CH₂CH₂N⁺(CH₃)₃ and -P(O⁻)CH₂CH₂CH₂N⁺(CH₃)₃ interacted equally well with cholesterol, as estimated by these permeability studies.     

Synthesis,structures and electrochemical properties of amino-derivatives of diiron azadithiolates as active site models of Fe-only hydrogenase

The preparation and characterization of two novel amino-incorporated sulfur-bridged dinuclear iron (I) complexes of the type [NR(μ-SCH₂)₂]Fe₂(CO)₆, one being amino protected [N(CH₂CH₂NHTs)(μ-SCH₂)₂]Fe₂(CO)₆ (8) and the other [(μ- SCH₂)₂Fe₂(CO)₆NCH₂CH₂N (μ-SCH₂)₂]Fe₂(CO)₆ (9) are described. These two complexes are readily prepared in a S_N2 manner between double lithium anion and bis(chloromethyl) amine derivatives. The structures of 8 and 9 were characterized by IR, ¹H, ¹³C NMR, MS and HRMS spectra and further determined by X-ray analyses. Protonation of complex 8 gave the mono N-protonated product, while for 9 the protonation occurred in both of the N atoms. The redox properties were evaluated by cyclic voltammograms. It was shown that these two complexes can catalyze electrochemical reduction of proton to molecular hydrogen.     

Coupled Na+ -K+ transport in vesicles containing a purified (NaK)-ATPase and only phosphatidyl choline.

Endogenous phospholipids of a purified (NaK)-ATPase were displaced by exogenous phosphatidyl choline. If vesicles were made from phosphatidyl choline and enzyme containing only phosphatidyl choline, coupled Na⁺K⁺ transport could be demonstrated. This transport was inhibitable by ouabain. Therefore, the number of components necessary for Na⁺K⁺ transport has been reduced to the purified (NaK)-ATPase and one phospholipid.     

Effect of transmembrane electrical potential and micelle geometry on phospholipid head group conformation

Phospholipid head group conformation has been measured in egg phosphatidyl choline vesicles with a transmembrane electrical potential. Using ³¹P NMR, the proton source of the ³¹P[¹H] nuclear Overhauser effect has been determined and the head group conformation shown to be unperturbed by a transmembrane electrical potential near 60 mV. The same technique was used to probe polar head group conformation in lysophosphatidyl choline micelles. The geometric constraints of the micelle structure force the head groups apart, preventing the intermolecular head group interactions found in phosphatidyl choline bilayers.     

On the identification of ionic species of neutral halogen dimers, monomers and pincer type palladacycles in solution by electrospray mass and tandem mass spectrometry

Electrospray (ESI) mass spectra analysis of acetonitrile solutions of a series of neutral chloro dimers, pincer type, and monomeric palladacycles has enabled the detection of several of their derived ionic species. The monometallic cationic complexes Pd[κ¹-C,κ¹-N,κ¹-S-C(CH₃S-2-C₆H₄)C(Cl)CH₂N(CH₃)₂]⁺ (1a) and [Pd[κ¹-C,κ¹-N,κ¹-S-C(CH₃S-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](CH₃CN)]⁺ (1b) and the bimetallic cationic complex [κ¹-C,κ¹-N,κ¹-S-C(CH₃S-2-C₆H₄)C(Cl)CH₂N(CH₃)₂]Pd-Cl-Pd[κ¹-C,κ¹-N,κ¹-S-C(CH₃S-2-C₆H₄)C(Cl)CH₂N(CH₃)₂]⁺ (1c) were detected from an acetonitrile solution of the pincer palladacycles Pd[κ¹-C,κ¹-N,κ¹-S-C(CH₃S-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](Cl) 1. For the dimeric compounds {Pd[κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](μ-Cl)}₂ (2, Y=H and 3, CF₃), highly electronically unsaturated palladacycles [Pd[κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂]⁺ (2d, 3d) and their mono and di-acetonitrile adducts, namely, [Pd[κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](CH₃CN)]⁺ (2e, 3e) and [Pd[κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](CH₃CN)₂]⁺ (2f and 3f) were detected together with the bimetallic complex [Pd[κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂]-Cl-Pd[κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N](CH₃)₂]⁺ (2a, 3a) and its acetonitrile adducts [κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](CH₃CN)Pd-Cl-Pd[ κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂]⁺ (2b, 3b) and [κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](CH₃CN)Pd-Cl-Pd[κ¹-C, κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂(CH₃CN)]⁺ (2c, 3c). The dimeric palladacycle {Pd[κ¹-C,κ¹-N-C(CH₃O-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](μ-Cl)}₂ (4) is unique as it behaves as a pincer type compound with the OCH₃ substituent acting as an intramolecular coordinating group which prevents acetonitrile full coordination, thus forming the cationic complexes [(C₆H₄(o-CH₃O)CC(Cl)CH₂N(CH₃)₂-κO,κC,κN)Pd]⁺ (4b), [(C₆H₄(o-CH₃O)CC(Cl)CH₂N(CH₃)₂- κO,κC,κN)Pd(CH₃CN)]⁺ (4c) and [(C₆H₄ (o-MeO)CC(Cl)CH₂N(CH₃)₂-κO, κC,κN)Pd-Cl-Pd(C₆H₄(o-CH₃O)CC(Cl)CH₂N(CH₃)₂-κO,κC,κN)]⁺ (4a). ESI-MS spectra analysis of acetonitrile solutions of the monomeric palladacycles Pd[κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](Cl)(Py) (5, Y=H and 6, Y=CF₃) allows the detection of some of the same species observed in the spectra of the dimeric palladacycles, i.e., monometallic cationic 2d-3d, 2e-3e and {Pd[κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](Py)}⁺ (5a, 6a) and {Pd[κ¹-C,κ¹-N-C(Y-2-C₆H₄)C(Cl)CH₂N(CH₃)₂](CH₃CN)(Py)}⁺ (5b, 6b) and the bimetallic 2a, 3a, 2b, 3b, 2c and 3c. In all cationic complexes detected by ESI-MS, the cyclometallated moiety was intact indicating the high stability of the four or six electron anionic chelate ligands. The anionic (chloride) or neutral (pyridine) ligands are, however, easily replaced by the acetonitrile solvent.     

Hexanuclear copper(II) complex of a novel poly(pyridine) ligand exhibiting unique long distance ferromagnetic interactions through a nitrato-O,O bridge

A novel hexanuclear copper complex [Cu₆(NO₃)₁₂(opytrizediam)₂(H₂O)][(CH₃)₂CO]_0.5(CH₃CH₂CH₂OH)_0.5 (1) with a NO₃ bridge has been synthesized by reaction of Cu(NO₃)₂ · 3H₂O with the new potentially octadentate ligand opytrizediam in n-propanol/acetone solution (opytrizediam=N,N^′-{2,4-di[(di-pyridin-2-yl)amine]-1,3,5-triazine} ethylenediamine). A single-crystal X-ray diffraction analysis showed the presence of six structurally different copper centres. The coordination spheres of four copper(II) ions are best described as square-pyramidal CuN₂O₃ chromophores while the two other copper(II) ions are in a trigonal-bipyramidal CuN₄O environment. Variable-temperature studies on 1 revealed a unique ferromagnetic coupling of two copper(II) ions bridged by a didentate nitrate anion and separated by a distance of 6.391(6) Å, with J=8.6(1) cm⁻¹.     

Lipids from Sugar Beet in Relation to the Preparation and Properties of (Sodium + Potassium)-Activated Adenosine Triphosphatases

Field grown leaves of sugar beet contained 0.89% of their fresh weight as chloroform : methanol 1 :2 extractable material, whereas climate chamber grown material contained 0.34, 0.15, and 0.16% in leaves, stalks, and roots respectively. A striking feature was the high proportion of sulfolipid: 7% of the total extractable of the field grown leaves, 19.5, 28.0, and 37.0% of the total extractable of respectively leaves, stalks, and roots from the climate chamber grown material. Among the fatty acids, all chain lengths from C₁₂ to C₂₈ were found, except only C₁₇ and C₁₉—Exceptionally high contents of fatty acids with a chain length of C₂₆ or C₂₈ were noted in some cases. The 2500–20,000 g fraction of root homogenates contained 19% of the total root lipids. Almost all of the phosphatidyl choline and about half of the phosphatidyl ethanolamine, but only 5% of the sulfolipid followed the fraction. A fractionation of conjugate lipid types was evident, with a loss of 18/2 and 18/3 conjugates, and with an increase in the proportions of 16/0 and, possibly, of the long-chain (around C₂₆) conjugates. The unspecific ATPase activity of the 2500–20,000 g fraction was rendered specific for (Na⁺+ K⁺) stimulation by treatment with 0.1% deoxycholate for 1 hour. This induced a more than 2-fold swelling of the preparation. About half of its total lipids were lost. Again, this loss was a fractional one, so that the phosphatidyl choline lost its long-chain (about C₂₆) fatty acid conjugate while the short to medium length chain conjugates remained; whereas the reverse was the case with the sulfolipid. The ATPase activity of the 2500–20,000 g fraction was destroyed by a 24 hour treatment with deoxycholate. As compared with the 1 hour treatment, the preparation lost about 20% both of its volume and of its chloroform : methanol extractable material. The quantitatively dominating loss was found in the (pigment + neutral fat) fraction. The monogalactosyl diglyceride, the phosphatidyl inositol, and a strongly acidic unknown fraction survived the deoxycholate treatments comparatively well. In the sulfolipid the fractionating effect of the prolonged deoxycholate treatment expressed itself as a loss mainly from the long-chain (about C₂₆) fatty acid conjugate. The (Na⁺+ K⁺) stimulation of the ATPase function of the particulate preparation is thus correlated with the balance between the long-chain (about C₂₆) fatty acid conjugates of zwitterionic phosphatidyl choline and anionic sulfolipid. This is of theoretical interest, since it indicates that the specific lipid composition under appropriate conditions may influence the charge and conformation of a lipoprotein complex, thereby determining its functional capacities.     

Theoretical Conformational Analysis in the Determination of Productive Conformations of Substrates for Acetylcholinesterase and Butyrylcholinesterase

All the equilibrium conformations of 34 analogues of acetylcholine (ACh) with the general formula R-C(O)O-Alk-N⁺(CH₃)₃ are calculated by the method of molecular mechanics. In the series R-C(O)O-(CH₂)₂-N⁺(CH₃)₃, a reliable correlation is found between the molecular volume of the substrate and the rate of its hydrolysis by acetylcholinesterase (AChE); the absence of such a correlation is demonstrated for butyryl-cholinesterase (BChE). Theoretical conformational analysis confirms that the completely extended tt conformation of ACh is productive for the hydrolysis by AChE, which agrees with the results of X-ray analysis of AChE. AChE is shown to hydrolyze only those substrates that form equilibrium conformers compatible in the mutual arrangement of trimethylammonium group, carbonyl carbon, and carbonyl oxygen with the tt conformation of ACh; in this case, the rate of substrate hydrolysis depends on the total population of these conformers. A reliable correlation was found between the population of the semifolded (tg^?) conformation of the choline moiety of substrate molecules and rate of their BChE hydrolysis. In a series of CH₃-C(O)O-Alk-N⁺(CH₃)₃, the rate of BChE hydrolysis is demonstrated to depend on the total population of conformations compatible in the mutual arrangement of functionally important atoms with the tg^? conformation of ACh. The tg^? conformation of ACh is concluded to be productive for BChE hydrolysis. Similar orientations of the substrate molecules relative to the catalytic triads of both AChE and BChE are proven to coincide upon the substrate productive sorption in their active sites. It is hypothesized that the sorption stage is rate-limiting in cholinesterase hydrolysis and the enzyme hydrolyzes the ACh molecule in its energetically favorable conformation.     

Synthesis, structure and optic properties of 2-methylimidazolium and 2-phenylimidazolium uranyl acetates

Two new salts based on heterocyclic organic cations and uranyl triacetate anion were obtained via reaction of zinc uranyl acetate with 2-substituted imidazoles in presence of an excess of acetic acid. Uranyl triacetate anion in [2-MeImH]⁺ [UO₂(CH₃COO)₃]⁻ and [2-PhImH]⁺ [UO₂(CH₃COO)₃]⁻ H₂O has an expected bipyramidal structure with linear uranyl group and three acetate groups laying in equatorial plane. [2-MeImH]⁺ [UO₂(CH₃COO)₃]⁻ structure analysis reveals H-bonded 1D chains connected through N-H···O hydrogen bonds. 2-phenylimidazolium in [2-PhImH]⁺ [UO₂(CH₃COO)₃]⁻ H₂O demonstrate planar geometry without any rotation of its rings, which was not registered before. H-bonds and π-π interactions of phenyl groups in this system lead to complicate 2D “sandwich” layer formation. The main features of IR- and luminescence spectrum of both compounds are also discussed.     

Effect of charge density of cationic polyelectrolytes on complex formation with DNA

The interaction between DNA and ionen polymers, -[N⁺(CH₃)₂(CH₂)_mN⁺(CH₃)₂(CH₂)_n], with m-n of 3–3, 6–6, and 6–10 were examined in order to know how the binding behavior of cationic polymers with DNA depends on the charge density of polycation. The ionen polymer has no bulky side chain and the binding forces with DNA would be attributed mainly to electrostatic interaction. When 3–3 ionen polymers were added to DNA solution, precipitable complexes with the ratio of cationic residue to DNA phosphate (+/?) of 1/1 and the free DNA molecules were segregated, while 6–6 and 6–10 ionen polymers formed soluble complexes with DNA molecules up to (+/?) = 0.5. This suggests that 3–3 ionen polymers bind cooperatively with DNA while 6–6 and 6–10 ionen polymers bind noncooperatively. The cooperative binding of 3–3 ionen polymer and the noncooperative binding of 6–6 ionen polymer were also supported by the thermal melting and recooling profiles from the midpoint between first and second meltings. It was concluded that the charge density of DNA phosphate is a critical value determining whether the ionen polymers bind to DNA by a cooperative or by a noncooperative binding, since the distance between successive cationic charges of 3–3 ionen polymer is shorter than that between successive phosphate charges on DNA double helix and those of 6–6 and 6–10 ionen polymers are longer.     

Biologically active bisquaternary ammonium chlorides: physico–chemical properties of long chain amphiphiles and their evaluation as non-viral vectors for gene delivery

The biological properties of bisquaternary ammonium salts, which are derivatives of N,N-bisdimethyl-1,2-ethanediamine (bis-C_nBEC), of general formula /C_nH_2n+1OOCCH₂(CH₃)₂N⁺CH₂CH₂N⁺(CH₃)₂CH₂COOC_nH_2n+1/2Cl⁻, were investigated (n=10, 12, 14). The interaction with model membrane was studied by differential scanning calorimetry experiments, and the apparent adiabatic molar compressibility of their solution as a function of concentration was obtained by sound velocity measurements. Their biological activities were assayed by Electrophoresis Mobility Shift, MTT proliferation, and transient transfection. All the investigated compounds interact with the DNA and are able to transfect DNA, when they are coformulated with DOPE, with an efficiency significantly greater than that of a standard commercial transfection reagent. Bis-C₁₄BEC is the only molecule able to deliver DNA inside the cells without a helper lipid, as shown by EGFP expression, albeit with a low efficiency in comparison with a standard commercial transfection reagent. This may be due to a slightly different interaction of bis-C₁₄BEC from bis-C₁₀BEC and bis-C₁₂BEC with phospholipid bilayers. Bis-C₁₀BEC and bis-C₁₂BEC show a slight fluidising effect, while bis-C₁₄BEC increases stability of both the gel and the rippled gel phases.     

Synthesis and structural characterization of trans-[Mo2(H2DMepyF)2(CH3CN)4](BF4)6 (HDMepyF=N,N-di(6-methyl-2-pyridyl)formamidine)

Reaction of Mo₂(O₂CCH₃)₂(DMepyF)₂ (HDMepyF=N,N^′-di(6-methyl-2-pyridyl)formamidine) with HBF₄ in CH₂Cl₂/CH₃CN afforded the complex trans-[Mo₂(H₂DMepyF)₂(CH₃CN)₄](BF₄)₆ (1), which crystallized in two forms, trans-[Mo₂(H₂DMepyF)₂(CH₃CN)₄](ax-CH₃CN)₂(BF ₄)₆ · 2CH₃CN (1a), and trans- [Mo₂(H₂DMepyF)₂(CH₃CN)₄](ax-BF₄) ₂(BF₄)₄ · 2CH₃CN (1b). The molecular structures of complexes (1) consist of two quadruply bonded molybdenum atoms, which are spanned by two trans-bridging formamidinate ligands and coordinated by four trans-CH₃CN. Each H₂DMepyF⁺ ligand adopts an s-cis,s-cis- conformation. The difference between 1a and 1b is that complex 1a contains two CH₃CN molecules as axial ligands, while 1b contains two BF₄⁻ anions as axial ligands. Complex 1 is the first dimolybdenum complex containing a pair of trans bridging ligands and two pairs of trans-CH₃CN ligands.     

Stability and thermodynamics of polyuridylic acid-deoxyadenosine complexes in aqueous neutral salt solutions

Using the thermodynamic analysis and methodology of Hill (Biopolymers, 12 , 257 (1973)) for the treatment of optical thermal transition data the effects of various neutral salt additives on the stability and thermodynamics of the poly U–deoxyadenosine interactions that lead to the formation of triple-stranded helical polymer–monomer complexes have been studied. In order of increasing molar effectiveness as polyU–deoxyadenosine complex stability perturbants (pH 7 and in the presence of 1 M NaCl), the various ions may be ranked: SO₄^?2 < Cl^? < Br^? < ClO₄^?; and (CH₃)₄ N⁺ < Li⁺ < Rb⁺ ～ Na⁺ < K⁺ < (CH₃ CH₂)₄ N⁺ < urea < Guan⁺ ～ (CH₃(CH₂)₂)₄ N⁺. Destabilizing neutral salt additives (e.g., NaClO₄) caused a decrease in the absolute magnitude of the apparent enthalpy and entropy of binding relative to the values determined in the presence of NaCl. By contrast, stabilizing additives (e.g., Na₂ SO₄) had the opposite effect on these parameters. Along a melting curve the apparent differential heat of complex formation calculated for the binding of deoxyadenosine to poly U in 1 M NaCl appeared to vary linearly with θ, the extent of fractional binding. For such a linear dependence it can be shown that the integral heat (usually determined calorimetrically) equals the differential heat at θ = 0.5. Correcting the apparent differential heat calculated at θ = 0.5 for ligand activity resulted in values for the integral heat of binding of deoxyadenosine to poly U in 1 M NaCl of ?13 to ?16 kcal/mol. Binding isotherms determined in the presence of different inorganic electrolytes could be superimposed provided that different temperatures were compared. However, the additive (CH₃)₄NCl, which has been shown to interact preferentially with A-T rich regions of DNA (Shapiro, Stannard, and Felsenfeld, Biochemistry, 8 , 3233 (1969)) resulted in a considerably broadened binding isotherm indicating less cooperativity.     

Theoretical study on electronic spectra and interaction in [Au3]-L-[Au3] (L = C6F6,Ag+) complexes

The electronic structure and spectroscopic properties of [Au₃(μ-C(OEt) = NC₆H₄CH₃)₃]_n-(C₆F₆)_m and [Au₃(μ-C²,N³-bzim)₃]_n-(Ag⁺)_m were studied at the B3LYP, PBE and TPSS levels. The interaction between the [Au₃] cluster and L (C₆F₆, Ag⁺) was analyzed. Grimme’s dispersion correction is used for those functionals. Weak π-interactions (Au-C₆F₆) were found to be the main contribution short-range stability in the models; while in the models with Ag⁺, an ionic interaction is obtained. The absorption spectra of these models at the PBE level agree with the experimental spectra.     

Dehydroisomerization of 1-pentene on the diruthenium disulfido complex

In situ generated [{Ru(P(OCH₃)₃)₂(CH₃CN)₃}₂(μ-S₂)]⁴⁺ (2), produced by abstracting the chloride atoms from [{Ru(P(OCH₃)₃)₂Cl}₂(μ-Cl)₂(μ-S₂)] (1) with Ag⁺ salts, reacts with 1-pentene in CH₃CN to afford [{Ru(P(OCH₃)₃)₂(CH₃CN)₃}₂{μ-SCH₂CHC(CH₃)CH₂S}]⁴⁺ (4) via dehydroisomerization of 1-pentene, and [{Ru(P(OCH₃)₃)₂(CH₃CN)₃}₂(μ-SCH₂CH₂CH(CH₂CH₃)S)]⁴⁺ (3), which is the reaction product from the reaction of the isolated 2 with 1-pentene.The elimination of two hydrogen atoms was confirmed by GC–MS analysis of the pentanes produced via disproportionation of two molecules of 1-pentene.In contrast, the reaction of in situ generated 2 with 1-hexene gave the cyclization product [{Ru(P(OCH₃)₃)₂(CH₃CN)₃}₂(μ-SCH₂CH₂CH(CH₂CH₂CH₃)S)]⁴⁺ (5) and a trace amount of the side product [{Ru(P(OCH₃)₃)₂(CH₃CN)₃}₂(μ-SSCH₂CHCHCH₂CH₂CH₃)]³⁺ (6) via elimination of H⁺ from the intermediate.Similarly, [{Ru(P(OCH₃)₃)₂(CH₃CN)₃}₂{μ-SCH₂CH₂CH(CH(CH₃)₂)S}]⁴⁺ (7) and [{Ru(P(OCH₃)₃)₂(CH₃CN)₃}₂{μ- SSCH₂CHCH(CH(CH₃)₂)S}]³⁺ (8) were obtained from the reaction of in situ generated 2 with 4-methyl-1-pentene.     

Influence of chain length on mono- versus di-alkylation in the reactivity of [Pt2(μ-S)2(PPh3)4] towards α,ω-dihalo-n-alkanes; a synthetic route to platinum(II) ω-haloalkylthiolate complexes

The reactions of [Pt₂(μ-S)₂(PPh₃)₄] with α,ω-dibromoalkanes Br(CH₂)_nBr (n = 4, 5, 6, 8, 12) gave mono-alkylated [Pt₂(μ-S){μ-S(CH₂)_nBr}(PPh₃)₄]⁺ and/or di-alkylated [Pt₂(μ-S(CH₂)_nS}(PPh₃)₄]²⁺ products, depending on the alkyl chain length and the reaction conditions. With longer chains (n = 8, 12), intramolecular di-alkylation does not proceed in refluxing methanol, with the mono-alkylated products [Pt₂(μ-S){μ-S(CH₂)_nBr}(PPh₃)₄]⁺ being the dominant products when excess alkylating agent is used. The bridged complex [{Pt₂(μ-S)₂(PPh₃)₄}₂{μ-(CH₂)₁₂}]²⁺ was accessible from the reaction of [Pt₂(μ-S)₂(PPh₃)₄] with 0.5 mol equivalents of Br(CH₂)₁₂Br. [Pt₂(μ-S){μ-S(CH₂)₄Br}(PPh₃)₄]⁺ can be cleanly isolated as its BPh₄⁻ salt, but undergoes facile intramolecular di-alkylation at −18 °C, giving the known species [Pt₂(μ-S(CH₂)₄S}(PPh₃)₄]²⁺. The reaction of I(CH₂)₆I with [Pt₂(μ-S)₂(PPh₃)₄] similarly gives [Pt₂(μ-S){μ-S(CH₂)₆I}(PPh₃)₄]⁺, which is fairly stable towards intramolecular di-alkylation once isolated. These reactions provide a facile route to ω-haloalkylthiolate complexes which are poorly defined in the literature. X-ray crystal structures of [Pt₂(μ-S){μ-S(CH₂)₅Br}(PPh₃)₄]BPh₄ and [Pt₂(μ-S(CH₂)₅S}(PPh₃)₄](BPh₄)₂ are reported, together with a study of these complexes by electrospray ionisation mass spectrometry. All complexes fragment by dissociation of PPh₃ ligands, and the bromoalkylthiolate complexes show additional fragment ions [Pt₂(μ-S){μ-S(CH₂)_n−2CHCH₂}(PPh₃)_m]⁺ (m = 2 or 3; m ≠ 4), most significant for n = 4, formed by elimination of HBr.     

Effect of N-alkyl-N,N,N-trimethylammonium ions on phosphatidylcholine model membrane structure as studied by 31P-NMR

The interaction of |C_nH_2n+1N⁺(CH₃)₃| · I^? (n = 3, 6, 9, 12, 14, 16 or 18) with egg-yolk phosphatidylcholine-water dispersions has been studied by ³¹P-NMR spectroscopy. It is shown that the effective anisotropy of ³¹P chemical shift (?Δσ_eff) of the lamellar phospholipid liquid-crystalline phase L_α increases with increasing concentration and alkyl chain length of the drug. Addition of $\text{|}\text{C}{}_6\text{H}{}_{13}\text{N}{}^{\mathrm{+}}\text{(CH}{}_3\text{)}{}_3\text{| ·I}{}^{\mathrm{?}}$ or |C₉H₁₉N⁺(CH₃)₃|·I^? to the phospholipid-water dispersion at a molar ratio ammonium salt:phospholipid > 0.8 induces in the dispersion a structure with an effective isotropic phospholipid motion. This structure is unstable and slowly transforms into the hexagonal phase. These effects have not been observed in phospholipid-water dispersions mixed with the ammonium derivatives with the longer alkyl chains n  12, 14, 16 or 18. It is proposed that these results might explain the effects of the investigated drugs on the nerve, muscle and bacterial cells.     

Differential regulation of the N-methyl transferases responsible for phosphatidylcholine synthesis in Saccharomyces cerevisiae

The enzymes catalyzing the conversion of phosphatidylethanolamine to phosphatidylcholine were assayed by measuring the incorporation of label from [¹⁴C-CH₃]-S-adenosyl-methionine into the endogenous phospholipids of particulate, cell-free preparations from S. cerevisiae grown in the presence of N-methylethanolamine, N,N-dimethylethanolamine, or choline. The results indicate that each base in the growth medium results in reduced levels of all the N-methyltransferase activity involved in the formation of the phosphatidyl ester of the given base. By following the conversion of exogenous [³²P]-phosphatidyldimethylethanolamine to [³²P]-phosphatidylcholine it has been shown that the activity of the third methyl transfer is 90% lower in particles prepared from choline grown cells than in particles prepared from cells grown without choline. The results suggest that there are at least two enzymes involved in the conversion of phosphatidylethanolamine to phosphatidylcholine and that their levels can be regulated individually.Supplementing the growth medium with any of the three methylated aminoethanols results in markedly increased cellular levels of their corresponding phosphatidyl esters and decreased levels of the precursor phosphatidyl esters. The fatty acid composition of phosphatidylcholine also changes when the medium is supplemented with choline suggesting that the proportions of the molecular species of this phosphatide depends on whether synthesis is via methylation of phosphatidylethanolamino or from the supplemented aminoethanol.     

Effects of choline and ethanolamine on the synthesis and breakdown of the inositol phospholipid (PI) system in Tetrahymena

Lower concentrations of choline chloride and ethanolamine (10^?3 M ; 10^?5 M ) increased phosphatidyl inositol (PI), phosphatidyl inositol monophosphate (PIP) and phosphatidyl inositol bisphosphate (PIP₂) level of Tetrahymena, while higher concentrations (10^?2 M ) decreased them. These two substances also influenced, however in a less obvious way, the transformation of inositol phospholipids. The experiments draw attention to the sensitivity of the precursors of the second messenger system at a phylogenetically low level.     

Resolution,structures, and vibrational circular dichroism of helicoidal trinickel and tricobalt paddlewheel complexes

It has been recently shown that enantiomers of the helicoidal paddlewheel complex [Co₃(dpa)₄(CH₃CN)₂]²⁺ (dpa = the anion of 2,2′-dipyridylamine) can be resolved using the chiral [As₂(tartrate)₂]²⁻ anion (AsT) and that these complexes demonstrate a strong chiroptical response in the ultraviolet-visible and X-ray energy regions. Here we report that the nickel congener, [Ni₃(dpa)₄(CH₃CN)₂]²⁺, can likewise be resolved using AsT. Depending on the stereochemistry of the enantiopure AsT anion, one or the other of the trinickel enantiomers crystallize from CH₃CN and diethyl ether in space group P42₁2 as the (NBu₄)₂[Ni₃(dpa)₄(CH₃CN)₂](AsT)₂·[solvent] salt. After resolution, the AsT salts were converted into the PF₆⁻ salts by anion exchange, with retention of the chirality of the trinickel complex. The enantiopure [Ni₃(dpa)₄(CH₃CN)₂](PF₆)₂·2CH₃CN and [Co₃(dpa)₄(CH₃CN)₂](PF₆)₂·CH₃CN·C₄H₁₀O compounds crystallize in space groups C2 and P2₁, respectively. Both the Ni(II) and Co(II) complex cations are stable towards racemization in CH₃CN. Vibrational circular dichroism (VCD) data obtained in CD₃CN demonstrate the expected mirror image spectra for the enantiomers, the observed peaks arising from the dpa ligand. The VCD response is significant, with Δε values up to 6 Lmol⁻¹ cm⁻¹ and vibrational dissymmetry factors on the order of 10⁻³. Density functional theory calculations well reproduce the experimental spectra, showing little difference between the peak position, sign, and intensity in the VCD for the cobalt and nickel complexes. These results suggest that VCD enhancement of these peaks is unlikely, and their remarkable intensity may be due to their rigid helicoidal structure.