Intermolecular/interionic interactions in l-isoleucine-, l-proline-, and l-glutamine-aqueous electrolyte systems

Speed of sound and density values for ternary systems (amino acid + salt + water): l-isoleucine/l-proline/l-glutamine in aqueous solutions of 1.5 M KCl, 1 M KNO₃, and 0.5 M K₂SO₄ have been measured for several concentrations of amino acids at different temperatures (303.15, 308.15, 313.15, 318.15, and 323.15 K). Using speed of sound and density data, the thermodynamic parameters such as isentropic compressibility (κ_s), change in isentropic compressibility (Δκ_s) and relative change (Δκ_s/κ₀) in isentropic compressibility have been computed. The isentropic compressibility values decrease with increase in the amino acid concentration as well as with temperature. The decrease in κ_s values with increase in concentration of l-isoleucine/l-proline/l-glutamine in 1.5 M KCl, 1 M KNO₃, and 0.5 M K₂SO₄ has been ascribed to an increase in the number of incompressible zwitterions in solutions, and the formation of ‘zwitterions-ions’ and ‘zwitterions-water dipole’ entities in solutions. The decrease in κ_s values with increase in temperature has been attributed to the corresponding decrease of κ_relax (a relaxational part of compressibility), which is dominant over the corresponding increase of κ_∞ (an instantaneous part of compressibility). The trends of variation of Δκ_s and Δκ_s/κ₀ with variations in solute concentration and temperature have also been discussed in terms of solute-solute and solute-solvent intermolecular/interionic interactions operative in the systems.     

Interactions of aluminum(III) with the biologically relevant ligand d-ribose

Aluminum(III) can be absorbed when it is appropriately complexed. There are several plasma components which can bind weakly Al(III). Many proteins bind Al(III) in solution quite strongly. Carbohydrates bearing an abundance of electronegative functional groups can interact with metal cations. In solution, d-ribose exists as a mixture at equilibrium of many isomers and only a few of them bear a ‘complexing’ sequence of the hydroxyl groups. The presence of d-ribose in an Al(III) solution experiences a decrease of its Brönsted-acid sites. The lowering of the Brönsted acidity of an Al(III)-d-ribose mixture suggests the existence of attractive interactions (‘association’) between Al(III) ion and the complexing sequence of the hydroxyls of d-ribose. There is enhancement in the stability of the interaction complexes between Al(III) and d-ribose through strong intramolecular hydrogen bonding, which offers the possibility to investigate the kinetics of the subsequent proton release reactions. On the basis of the kinetic results, it may be concluded that proton release reactions, which are associated with the complexation reactions, are associatively activated. The complexes (Al(H₂O)_6−n(d-ribose_−nH)⁽³⁻ⁿ⁾⁺) resulting from the various ‘complexing’ forms of d-ribose are formed at mainly acidic pH. As the pH increases, the values of the activation enthalpy, ΔH^≠, are changing, because of the formation of mixed hydroxo-complexes (Al(H₂O)_6−n−m(OH)_m(d-ribose_−nH)^(3−n−m)+); finally, OH⁻ displaces d-ribose from the coordination sphere of Al(III) in a rather slow process, i.e. with high values of ΔH^≠; the activation enthalpy values, ΔH^≠, decrease with the progression of the displacement, becoming finally very small due to the formation of a precipitate. Chelate coordination of d-ribose with some divalent and trivalent metal ions has been also reported.     

Selection of synthetic receptors capable of sensing the difference in binding of d-Ala-d-Ala or d-Ala-d-Lac ligands by screening of a combinatorial CTV-based library

Screening of a combinatorial CTV-based artificial, synthetic receptor library 1 {1-13, 1-13, 1-13} for binding of a variety d-Ala-d-Ala and d-Ala-d-Lac containing ligands (6-11) was carried out in phosphate buffer (0.1 N, pH=7.0). After screening and Edman sequencing, synthetic receptors were found containing amino acid sequences, which are either characteristic for binding dye labeled d-Ala-d-Ala or d-Ala-d-Lac containing ligands. For example, receptors capable of binding d-Ala-d-Ala containing ligands 6, 7, 9 and 11 contained—almost in all cases—at least one basic amino acid residue—predominantly Lys—in their arms. This was really a striking difference with the arms of the receptors capable of binding d-Ala-d-Lac containing ligands 8 and 10, which usually contained a significant number of polar amino acids (Gln and Ser), especially in ligand 8, but hardly any basic amino acids. Use of different (fluorescent) dye labels showed that the label has a profound, albeit not decisive, influence on the binding by the receptor. A hit from the screening of the CTV-library with FITC-peptidoglycan (6) was selected for resynthesis and validation.     

Kinetics of thermo-oxidative and thermal degradation of poly(d,l-lactide) (PDLLA) at processing temperature

Poly(d,l-lactide) (PDLLA) degraded at processing temperature under air and nitrogen. A random chain scission model was established and used to determine the activation energy E_a, and FT-IR, ¹H and ¹³C NMR were used to elucidate the degradation behavior under different atmospheres. Results showed that there were two to three stages. The 1st stage was dominated by the oligomers containing carboxylic acid groups and hydroxyl groups, during which oxygen and nitrogen had little effect on the degradation, thus they share similar E_a. When the oligomers were consumed over or evaporated, the 2nd stage began, and oxygen had a promoting effect on the thermo-oxidation process, resulting in the great decrease in E_a. The third stage of PDLLA was observed when it degraded under nitrogen over 200 °C, which was caused by the appearance of carboxylic acid substance.     

One-pot inversion of d-mannono-1,4-lactone for the practical synthesis of l-ribose

l-Ribose was synthesized in a concise manner from d-mannono-1,4-lactone using one-pot inversion conditions. Treatment of d-mannono-1,4-lactone with piperidine, followed by mesylation-induced S_N2-type O-alkylation, afforded the desired one-pot inversion in an optimum yield, and the following straightforward transformations provided l-ribose in good yields.     

A d,l-proline catalyzed diastereoselective trimolecular condensation: an approach to the one-pot synthesis of perhydrofuro[3,2-b]pyran-5-ones

d,l-Proline was found to catalyze efficiently the one-pot trimolecular condensation of indoles, a sugar hydroxyaldehyde, and Meldrum’s acid followed by intramolecular cyclization with evolution of carbon dioxide and elimination of acetone to afford 7-(1H-3-indolyl)-2,3-dimethoxyperhydrofuro[3,2-b]pyran-5-ones. The reaction proceeded cleanly at ambient temperature to afford the products in good yields with high diastereoselectivity.     

Improved synthesis of 6-amino-6-deoxy-d-galactono-1,6-lactam and d-mannono-1,6-lactam from corresponding unprotected d-hexono-1,4-lactones

Regioselective bromination of unprotected d-galactono-1,4-lactone and d-mannono-1,4-lactone with PPh₃/CBr₄ led to 6-bromo-6-deoxy derivatives. These intermediates were treated with LiN₃ and hydrogenated to give 6-amino-6-deoxy-d-galactono-1,6-lactam (8) and 6-amino-6-deoxy-d-mannono-1,6-lactam (13) in 74 and 67% overall yield, respectively.     

Biodegradable poly(l-lactic acid) nanofiber prepared by a carbon dioxide laser supersonic drawing

Biodegradable poly(l-lactic acid) (PLLA) nanofiber was prepared by a carbon dioxide (CO₂) laser supersonic drawing which was carried out by irradiating the laser on an as-spun fiber in a supersonic jet. The supersonic jet was generated by blowing off air into a vacuum chamber from a fiber supplying orifice. The flow velocity from the orifice can be estimated by applying Graham’s theorem from the pressure difference between the atmospheric pressure and the pressure of the vacuum chamber. The fastest flow velocity estimated was 396 m s⁻¹ when the chamber pressure was 6 kPa. The PLLA nanofiber having an average diameter of 0.132 μm was obtained when the supersonic drawing was carried out by irradiating the laser at 177 W cm⁻² on the as-spun fiber supplied at 0.1 m min⁻¹ in the vacuum chamber at 6 kPa. The obtained nanofiber had a draw ratio of about 323,000 and a degree of crystallinity of 45%, and its diameter uniformity was high. The CO₂ laser supersonic drawing was a new route for preparation of various nanofibers without using any solvent.     

An efficient synthesis of d-ribo-C18-phytosphingosine and l-arabino-C18-phytosphingosine from d-fructose

d-ribo-C₁₈-phytosphingosine and l-arabino-C₁₈-phytosphingosine were synthesised starting from commercially inexpensive d-fructose. Metal-mediated fragmentation and stereoselective reduction were used as key steps to provide the hydrophilic portion of d-ribo and l-arabino phytosphingosines. Grubbs’ cross-metathesis and hydrogenation allowed the incorporation of hydrophobic tail.     

Racemization behavior of l,l-lactide during heating

To control the depolymerization process of poly(l-lactic acid) into l,l-lactide for feedstock recycling, the racemization of l,l-lactide as a post-depolymerization reaction was investigated. In the absence of a catalyst, the conversion to meso-lactide increased with increase in the heating temperature and time at a higher rate than the conversion into oligomers. The resulting high composition of meso-lactide suggests that the direct racemization of l,l-lactide had occurred in addition to the known racemization mechanism that occurs on the oligomer chains. In the presence of MgO, the oligomerization rapidly proceeded to reach an equilibrium state between monomers and oligomers. The equilibrium among l,l-, meso-, and d,d-lactides was found to be a convergent composition ratio l,l-:meso-:d,d-lactides = 1:1.22:0.99 (wt/wt/wt) after 120 min at 300 °C. This composition ratio also indicates that in addition to the known racemization reaction on the oligomer chains, direct racemization among the lactides is also a frequent occurrence.     

Influence of hydrolytic degradation on the surface properties of poly-5d/95l-lactide resorbable bone plates

This study explores in vitro aging effects on the surface properties of resorbable PLA95 (poly-5d/95l-lactide) bone plates. The in vitro degradation of injection molded PLA95 bone plates was undertaken by soaking them in a PBS solution. Specimens were harvested at 0, 4, 6, 8, 12, 20, and 26 weeks. After each in vitro aging period, the surface morphology, viscosity, chemical structure, wettability, and thermal properties of the PLA95 bone plates were examined by scanning electron microscopy (SEM), capillary viscometers, attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR), contact angle, and modulated differential scanning calorimetry (MDSC), respectively. The surface morphology of aged PLA95 bone plates exhibited bulk erosion. As hydrolysis progressed, the inherent viscosity (I.V.) of the PLA95 plates gradually decreased from 0.83 ± 0.01 dL/g at week 0-0.46 ± 0.03 dL/g at week 26. However, the absorbance peak intensity ratio between δ_{as CH3} (A_1452 cm⁻¹) and ν_CO (A_1750 cm⁻¹) and the contact angle reveal different tendencies than that of molecular weight, which decreases. The contact angle of the PLA95 plates decreased until week 4, increased until week 8, and subsequently decreased again. Peak separation analysis reveals that the equilibrium part of the modulated DSC overlapped curves exhibit triple endothermic peaks. Over time, in vitro degradation changes the position and area of the individual peaks. After different time periods of degradation, the variation of wettability shows a tendency similar to the change of PLA95 plates crystallinity; the intensity ratio of A_1452 cm⁻¹ and A_1750 cm⁻¹ (δ_{as CH3}/ν _CO) absorbance peaks varied like the ratio of β/α-crystal heat of fusion. Results also show a similarity in the degradation time dependence in MDSC, contact angle, and ATR-FTIR measurements. During the in vitro aging process, the breakdown and subsequent recrystallization of PLA95 molecular chains might be attributed to a progressive change in wettability and the molecular conformation between δ_{as CH3} and ν_CO.     

Intermolecular/interionic interactions in l-leucine-, l-asparagine-, and glycylglycine-aqueous electrolyte systems

Ultrasonic velocity and density values have been measured for ternary systems (amino acid/di-peptide + salt + water): l-leucine/l-asparagine/glycylglycine each in 1.5 M aqueous solutions of NaCl or NaNO₃ or KNO₃ used as solvents for several concentrations of amino acids/di-peptide at different temperatures in the range of 298.15-323.15 K. The ultrasonic velocity values have been found to increase with increase in amino acids/di-peptide concentration and temperature in all the systems. The increase in ultrasonic velocity with increase in concentration has been discussed in terms of electrostatic interactions occurring between terminal groups of zwitterions (NH₄⁺ and COO⁻) and Na⁺, K⁺, Cl⁻, NO₃⁻ ions. The interactions of water dipoles with cations/anions and with zwitterions have also been taken into consideration. It has been observed that the ion-zwitterion and ion-dipole attractive forces are stronger than those of ion-hydrophobic repulsive forces. These interactions comprehensively introduce the cohesion into solutions under investigation. The cohesive forces are further enhanced on successive increases in solute concentration. Using ultrasonic velocity and density data, the parameters such as isentropic compressibility (κ_s), change (Δκ_s) and relative change (Δκ_s/κ₀) in isentropic compressibility, specific acoustic impedance (Z) and relative association (RA) have been computed. The isentropic compressibility values decrease with increase in the concentration of solutes as well as with temperature. The decrease in κ_s values with increase in concentration of l-leucine, l-asparagine and glycylglycine in 1.5 M aqueous solutions of NaCl, NaNO₃ and KNO₃ have been explained in terms of an increase in the number of incompressible molecules/zwitterions in solutions and the formation of compact zwitterions-water dipole and zwitterions-ions structures in solutions. The decrease in κ_s values with increase in temperature has been attributed to the corresponding decrease of κ_relax. (relaxational part of compressibility)_, which is dominant over the corresponding increase of κ_∞ (instantaneous part of compressibility). The trends of variations of Δκ_s, Δκ_s/κ₀, Z and RA with change of concentration and temperature have also been interpreted in terms of various intermolecular/interionic interactions existing in the systems.     

Efficient synthesis of new N-alkyl-d-ribono-1,5-lactams from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 9a in quantitative yield. Bromination of amide 9a by the system SOBr₂ in DMF or PPh₃/CBr₄ in pyridine led, after acetylation, to epoxide 7. However, treatment of amide 9a with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxyl-N-ethyl-d-ribonamide 10a. Methanolysis of 10a, with sodium methoxide, afforded the N-ethyl-d-ribonolactam 11a in 51% overall yields. Using this method, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonolactams 11b-e were obtained in good yields (48-53%).     

Prevailing mechanisms of the hydrolytic degradation of oligo(d,l-lactide)-grafted dextrans

The predominant mechanism of the hydrolytic degradation of oligo(d,l-lactide)-grafted dextrans in phosphate buffer was followed by quantifying both released dextran and lactic acid from the copolymers. The studied amphiphilic copolymers, with well-defined structure, exhibited various oligo(d,l-lactide) weight fractions (F^OLA) while having a quite high extent of free hydroxyl groups (>90%). Depending on their F^OLA, oligo(d,l-lactide)-grafted dextrans were soluble either in water or in organic solvents (THF, toluene, …) and different prevailing mechanisms of hydrolytic degradation were observed. The copolymer soluble in THF, with longer oligo(d,l-lactide) grafts and higher F^OLA, was found to degrade via a particular mechanism by which the greatest part of dextran was released into buffer medium during the first two weeks of degradation. During the initial stage of degradation, the hydrophilicity of dextran backbone was considered to be the main driving force for the hydrolytic cleavage of the ester linkage between backbone and grafts. Released oligo(d,l-lactide) grafts were found to be degraded via chain-end degradation or random degradation depending on their solubility in buffer medium. In case of water-soluble copolymers with shorter oligo(d,l-lactide) grafts and lower F^OLA, the chain-end degradation was exclusively observed.     

Effects of molecular weight and small amounts of d-lactide units on hydrolytic degradation of poly(l-lactic acid)s

Films of poly(l-lactic acid) (PLLA) with different number-average molecular weights (M_n) and d-lactide unit contents (X_d) were made amorphous and the effects of molecular weight and small amounts of d-lactide units on the hydrolytic degradation behavior in phosphate-buffered solution at 37 °C of PLLA were investigated. The degraded films were investigated using gravimetry, gel permeation chromatography, polarimetry, differential scanning calorimetry, X-ray diffractometry, and tensile testing. To exclude the effects of crystallinity on the hydrolytic degradation, the films were made amorphous by melt-quenching. The incorporation of small amounts of d-lactide units drastically enhanced the hydrolytic degradation of PLLA. In the period of 0-32 weeks, the hydrolytic degradation rate constant (k) of PLLA films increased with increasing X_d, while the k values did not depend on M_n. This means that the effects of X_d on the hydrolytic degradation rate of the films are higher than those of M_n. In contrast, in the period of 32-60 weeks neither X_d nor M_n was a crucial parameter to determine k values, probably because in addition to these parameters the differences in the amount of catalytic oligomers accumulated in films and crystallinity affect the hydrolytic degradation behavior of the films. The initially amorphous PLLA films remained amorphous even after the hydrolytic degradation for 60 weeks.     

Glycine and l-glutamic acid-based dendritic gelators

Novel dendrons based on glycine and l-glutamic acid from the first generation (G1) to the third generation (G3) were synthesized and studied for their gelation properties by using transmission electron microscopy (TEM), atomic force microscopy (AFM), fluorescence, IR, circular dichroism (CD), and ¹H NMR spectroscopy. It was found that the gelation capability of these dendrons increased from the first generation (G1) to the third generation (G3), and that G3 exhibited the highest efficiency in forming gels. Both the focal and peripheral groups of dendrons had great effects on the formation of organogels. Hydrogen bonding and π-π stacking interactions were proved to be the main driving forces to form the fibrous networks at low concentrations (0.5 wt %). Small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD) measurements indicate that the xerogels of the second generation (G2) from ethyl acetate and ethanol, and G3 xerogel from CH₂Cl₂ all display lamellar structures with the interlamellar spacing of ca. 36.0 Å for G2 and 40.5 Å for G3, respectively.     

New Sn(IV) and Ti(IV) bis(trimethylsilyl)amides in d,l-lactide polymerization, SEM characterization of polymers

Ring-opening polymerization of d,l-lactide initiated with new chlorotris(bis(trimethylsilyl) amido) tin(IV), tetrakis(bis(trimethylsilyl)amido) tin(IV) and titanium(IV) was investigated. New complexes reveal practically quantitative conversion degrees and produced polymers with higher molecular weight with respect to reference alkoxo-species.The X-ray crystal structure of chlorotris(bis(trimethylsilyl)amido) tin (IV) was investigated. Axial enantiomerism of [SnCl{N(SiMe₃)₂}₃] molecules in solution was studied by high-field dynamic NMR, the value of Gibbs activation energy ΔG^‡ = 59.5 kJ/mol.Field emission SEM investigation of bulk polymer samples and thin films on conductive Al foil revealed a stratified fibrous textures in the bulk polymers, as well as nanoscaled topographical features due to coils and entanglements of individual macromolecules in thin films.     

Amperometric simultaneous sensing system for d-glucose and l-lactate based on enzyme-modified bilayer electrodes

An amperometric biosensor system which uses screen-printed electrodes to simultaneously detect d-glucose and l-lactate has been developed and applied for simple and rapid determination of d-glucose and l-lactate levels in lactic fermenting beverages. The system was constructed from three-dimensionally layered electrodes. Taking into consideration the effects of easily oxidized substances contained in the samples, ferricyanide ions, which are electrochemically oxidized at a lower voltage, were chosen as a mediator. A linear relationship between steady-state current and concentration was found over a range of 1-100 mM (d-glucose) and 1-50 mM (l-lactate); the variation coefficients were 1.43% (n = 10) and 3.50% (n = 10) for the d-glucose and l-lactate sensors, respectively. When applied to lactic fermenting beverages, there was good agreement between the results obtained by the proposed sensing system and those obtained by the HPLC method. Using the proposed method, assays were completed within 5 min.     

A highly efficient synthesis of unnatural l-sugars from d-ribose

A preparative and short synthesis of l-ribose and l-apiose was accomplished starting from d-ribose via stereoselective cis-dihydroxylation and C2-hydroxymethylation, respectively. These l-sugars can serve as versatile intermediates for the synthesis of l-nucleosides.