DSC analysis of isothermal melt-crystallization, glass transition and melting behavior of poly(l-lactide) with different molecular weights

Isothermal melt-crystallization, glass transition and melting behavior of poly(l-lactide) (PLLA) with different molecular weights were investigated by using differential scanning calorimetry. Analysis by Avrami equation showed that crystallization was initiated by heterogeneous nucleation, followed by 3-dimensional growth. The maximum reciprocal half-time of crystallization (1/t_1/2) was detected at 105 °C. Double endothermic peaks were observed around the glass transition for PLLA with intermediate crystallinities, indicating the coexistence of bulk-like and confined amorphous regions. Double-melting behavior was analyzed and combined with the equilibrium melting temperature evaluation by non-linear Hoffman-Weeks extrapolation, from which a value of 207.6 °C was deduced for PLLA of infinite molecular weight. Lauritzen-Hoffman theory was employed to analyze the crystallization kinetics. Regime II-III transition was found to occur at 120 °C for PLLA of lower molecular weight. The crystal morphology was also examined by scanning electron microscopy through chemical etching method.     

Total synthesis of the proposed structure of `brahol' and the structural revision

Proposed structure of brahol, a natural product, has been disproved by total synthesis of the proposed molecule from myo-inositol. Readily available 1,2;4,5-di-O-isopropylidene-myo-inositol, 3 was converted to 2,5-di-O-acetyl-1,6;3,4-di-O-isopropylidene-allo-inositol by epimerization of the di-triflate of 3. The acetyl group at O-5-position was selectively deprotected by aminolysis or methanolysis enabling the total synthesis of 5-O-methyl-allo-inositol, the proposed structure of brahol in six steps from myo-inositol. A comparison of spectral data of synthetic 5-O-methyl-allo-inositol with that reported for natural brahol revealed that the proposed structure of brahol is incorrect. A detailed structural revision revealed that brahol is nothing but quebrachitol. This study contradicts the first and only report on the natural occurrence of allo-inositol derivative.     

Achievement of ring inversion of myo-inositol derivatives due to silyloxy/silyloxy repulsion enhanced by the trans-substituents on both sides

The introduction of quite bulky trialkyl or diarylalkylsilyl groups into vicinal trans-hydroxy groups induced a conformational flip of certain multifunctionalized cyclohexane rings from the usual chair form possessing more equatorial substituents (equatorial-rich chair form) into another chair-form that has more axial substituents (axial-rich chair form). This realization was experimentally revealed by the conformational study of the synthetic myo-inositol derivatives possessing two tert-butyldimethylsilyl (TBS), two triisopropylsilyl (TIPS), or two tert-butyldiphenylsilyl (TBDPS) groups on an adjacent trans-diol. Among them, the cyclohexane rings of the 4,5-bis-O-TIPS-myo-inositol, 4,5-bis-O-TBDPS-myo-inositol, and 1,2,3,6-tetra-O-benzyl-4,5-bis-O-TBDPS-myo-inositol were in the axial-rich chair form. Comparison of the ring conformations also revealed that the order of the repulsion was OTBDPS/OTBDPS>OTIPS/OTIPS>OTBS/OTBS, and the silyloxy/silyloxy repulsion was enhanced when the two silyloxy groups were placed in the center of the contiguous four equatorial substituents.     

A new sepharose derivative containing covalently boundmyo-inositol: Its structure and application

myo-Inositol was covalently bound on, an epoxy-activated sepharose. In order to elucidate the structure of the derivative of sepharose formed, in a model reactionmyo-inositol was coupled to propylene oxide, whereby two compounds were obtained. By NMR-spectroscopy,¹³C-resonancespectroscopy and gas chromatography substanceI could be characterized as a mixture of two isomers. Both are the product of a binding to the hydroxyl group on C-atom 2 ofmyo-inositol. The only difference seems to be the point of attachment to the side chain. SubstanceII, however, originates by substitution on an equitorial hydroxyl group. The application of this new affinity gel is reported.

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Ein neues Sepharose-Derivat mit kovalent gebundenem myo-Inosit: Struktur und Anwendung

Zusammenfassung myo-Inosit wurde an eine epoxy-aktivierte Sepharose kovalent gebunden. Zur Aufklärung der Struktur dieses Sepharosederivats wurde in einer Modellreaktionmyo-Inosit an Propylenoxid gekoppelt, wobei zwei Substanzen erhalten wurden. Durch NMR-Spektren,¹³C-Resonanzspektren und Gaschromatographie konnte SubstanzI als Gemisch zweier Isomerer charakterisiert werden. Beide sind durch Derivatisierung, am C-Atom 2 des Inosits entstanden, sie unterscheiden sich nur im Ort der Bindung an der Seitenkette. Bei SubstanzII ist hingegen die Substitution an einem äquatorialen O-Atom eingetreten.Es wird über die Anwendung des neuen Affinitätsgels berichtet.

     

Determination of myo-inositol in a flow-injection system with co-immobilized enzyme reactors and amperometric detection

A selective and sensitive flow-injection system for the determination of myo-inositol (hexahydroxycyclohexane) is described. Inositol dehydrogenase, IDH, lactate dehydrogenase, LDH, and lactate oxidase, LOD, are co-immobilized on porous glass and used in a packed-bed enzyme reactor. myo-Inositol reacts to produce an equivalent amount of hydrogen peroxide, which oxidizes hexacyanoferrate(II) to hexacyanoferrate(III) in a second reactor containing immobilized peroxidase. The hexacyanoferrate(III) is then detected amperometrically at 0 mV vs. SCE in a flow-through detector. The system responds linearly to injected samples of myo-inositol (25 μl) in the concentration range 1–300 μM. The maximum throughput was 90 samples per hour. The IDH/LDH/LOD reactor was stable for at least 5 weeks.     

Conformational study of the natural iron chelator myo-inositol 1,2,3-trisphosphate using restrained/flexible analogues and computational analysis

myo-Inositol 1,2,3-trisphosphate [Ins(1,2,3)P₃], a component in mammalian cells, possesses the correct chemical properties of an intracellular iron transit ligand. Here we have examined the conformation of the Ins(1,2,3)P₃-Fe³⁺ complex. The synthesis and antioxidant properties of 4,6-carbonate-myo-inositol 1,2,3,5-tetrakisphosphate [4,6-carbonate Ins(1,2,3,5)P₄], which is locked in the unstable penta-axial chair conformation and 1,2,3-trisphosphoglycerol, a flexible acyclic analogue of Ins(1,2,3)P₃, are reported. 4,6-Carbonate Ins(1,2,3,5)P₄ caused complete inhibition of iron-catalysed hydroxyl radical (HO) formation at 100 μM, thereby resembling Ins(1,2,3)P₃ and supporting a penta-axial chair binding conformation. In contrast, 1,2,3-trisphosphoglycerol was shown to have incomplete antioxidant properties. In support of experimental observations, we have applied high-level density functional calculations to the binding of Ins(1,2,3)P₃ to iron. This study provides evidence that Fe³⁺ binds tightly to the less stable penta-axial conformation of Ins(1,2,3)P₃ using terminal and bridging phosphate oxygens, thought to also contain a tightly bound water molecule or hydroxyl ligand in the complex.     

Influence of melting conditions on the thermal behaviour of poly(l-lactic acid)

The influence of melting temperature and time on the thermal behaviour of poly(l-lactic acid) (PLLA) was studied with differential scanning calorimetry (DSC). Different melting conditions were investigated at temperature ranging from 200 to 210 °C, and for time from 2 to 20 min. For lower-molecular-weight PLLA, a single exothermic peak could be observed at cooling rate of 2 °C/min, after melted at different conditions. The obtained peak temperature and degrees of crystallinity dramatically increased with an increase of melting temperature or time. During subsequent heating scans, double melting peaks could be observed, which were significantly affected by prior melting conditions. The degradation of this material in the melt and the melt/re-crystallization mechanism might be responsible for the observations above. Apart from double melting, double cold crystallization peaks were observed during heating traces for this material after fast cooling (20 °C/min) from the melt. Prior melting conditions could significantly influence the cold crystallization behaviour. The competition between the crystallization from the nuclei remained after cooling, and that from spontaneous nucleation might be responsible for the appearance of double peaks. Additionally, the influence of melting conditions on the thermal behaviour of PLLA was dependent on the initial molecular weight.     

Accelerated hydrolytic degradation of Poly(l-lactide)/Poly(d-lactide) stereocomplex up to late stage

Poly(l-lactide) (PLLA)/poly(d-lactide) (PDLA) blend specimens containing only stereocomplex as crystalline species, together with those of pure PLLA and PDLA specimens, were prepared by solution crystallization using acetonitrile as the solvent. Their accelerated hydrolytic degradation was carried out in phosphate-buffered solution at elevated temperatures of 70-97 °C up to the late stage. During hydrolytic degradation, the stereocomplex crystalline residues were first traced by gel permeation chromatography. Similar to the hydrolytic degradation of pure PLLA and PDLA specimens, the hydrolytic degradation of stereocomplexed PLLA/PDLA blend specimens slowed down at the late stage when most of the amorphous chains were removed and crystalline resides were formed and degraded. The estimated activation energy for hydrolytic degradation of stereocomplex crystalline residues (97.3 kJ mol⁻¹) is significantly higher than 75.2 kJ mol⁻¹ reported for α-form of PLLA crystalline residues. This indicates that the stereocomplex crystalline residues showed the higher hydrolysis resistance compared to that of α-form of PLLA crystalline residues.     

Miscibility and hydrolytic degradation in alkaline solution of poly(l-lactide) and poly(p-vinyl phenol) blends

Poly(l-lactide) (PLLA) was melt-blended with poly(p-vinyl phenol) (PVPh) using a two-roll mill, and the miscibility between PLLA and PVPh and degradation of the blend films were investigated. It was found that PLLA/PVPh blend has miscibility in the amorphous state because only single T_g was observed in the DSC and DMA measurements. The T_g of the PLLA/PVPh blend could be controlled in the temperature range from 55 °C to 117 °C by changing the PVPh weight fraction. In alkaline solution, degradation rate of PLLA/PVPh blends was faster than that of neat PLLA because PVPh could dissolve in alkaline solution. The surface morphology of degraded PLLA and PLLA/PVPh blend were observed by SEM. The surface morphology of degraded PLLA/PVPh blend was finer than that of PLLA. Young's modulus of PLLA/PVPh blend increased with increasing PVPh content. Yield stress of PLLA/PVPh blends whose PVPh content was less than 30 wt% kept the level of about 55 MPa and that of PLLA/PVPh blend whose PVPh content was 40 wt% is much lower than that of neat PLLA.     

A stannylene strategy for regioselective acylation and phosphorylation of 1,2-cyclohexylidene-myo-inositol. Its convenient resolution and phosphatidylinositol synthesis

The bis(dibutylstannylene) derivative of 1,2-cyclohexylidene-myo-inositol reacted with (S)-O-acetylmandeloyl chloride and diphosphate tetraesters to give 3,6-dimandelate and 3-phosphate, respectively. Using the stannylene methodology for the optical resolution and regioselective phosphorylation of the ketal, a concise synthesis of phosphatidylinositol with the natural configuration was accomplished.     

Cyclitol based metal complexing agents. Preference for the extraction of lithium by myo-inositol based crown-4-ethers depends on the relative orientation of crown ether oxygen atoms

myo-Inositol derived crown-4-ethers in which two of the oxygen atoms in the crown ether moiety have different relative orientations were prepared. Metal picrate binding studies revealed that the crown ether having 1,3-diaxial orientation shows the highest selectivity for binding to lithium although the crown ether having 1,2-diequatorial orientation exhibited the highest binding constant for lithium picrate. These results suggest that relative binding affinity of metal ions to crown ethers can be tuned by varying the relative orientation of crown ether oxygen atoms. The relevance of these results to the previously observed regioselectivity during the O-substitution of myo-inositol orthoesters is discussed.     

Enhanced crystallization,thermal properties,and hydrolysis resistance of poly(l-lactic acid) and its stereocomplex by incorporation of graphene nanoplatelets

Poly(d-lactic acid) (PDLA) and graphene nanoplatelets were used as nucleating agents for poly(l-lactic acid) (PLLA). The graphene (1 wt%) shows a more pronounced effect than PDLA in facilitating PLLA crystallization. Graphene effect on crystallization of stereocomplex (SC) polylactide is also demonstrated. Although medium molecular weight PLLA was blended with a limited content (1 wt%) of low molecular weight PDLA in the presence of graphene (0.5 phr), SC melting temperature is slightly increased without the use of high molecular weight polylactide pair. Also, optimal graphene content (0.5 phr–1.5 phr) promotes crystallization of PLLA homocrystals in the three-component system (PLLA/PDLA/graphene). Graphene additionally enhances Young's modulus and barrier property to thermal degradation of both PLLA and SC systems. Furthermore, PLLA/graphene is more resistant to hydrolysis than PLLA. Likewise, PLLA/PDLA/graphene is more stable than PLLA/PDLA during hydrolysis.     

Influence of graphene nanosheets on stereocomplex crystallization behaviors of star‐shaped poly (D(L)‐lactide) stereoblock copolymer

The nanocompsites of star‐shaped poly(D‐lactide)‐co‐poly(L‐lactide) stereoblock copolymers (s‐PDLA‐PLLA) with two‐dimensional graphene nanosheets (GNSs) were prepared by solution mixing method. Crystallization behaviors were investigated using differential scanning calorimetry, polarized optical microscopy, and wide angle X‐ray diffraction. The results of isothermal crystallization behaviors of the nanocompsites clearly indicated that the GNS could remarkably accelerate the overall crystallization rate of s‐PDLA‐PLLA copolymer. Unique stereocomplex crystallites with melting temperature about 207.0°C formed in isothermal crystallization for all samples. The crystallization temperatures of s‐PDLA‐PLLAs shifted to higher temperatures, and the crystallization peak shapes became sharper with increasing GNS contents. The maximum crystallization temperature of the sample with 3 wt% GNS was about 128.2°C, ie, 15°C higher than pure s‐PDLA‐PLLA. At isothermal crystallization processes, the halftime of crystallization (t_0.5) of the sample with 3 wt% GNS decreased to 6.4 minutes from 12.9 minutes of pure s‐PDLA‐PLLA at 160°C.The Avrami exponent n values for the nanocomposites samples were 2.6 to 3.0 indicating the crystallization mechanism with three‐dimensional heterogeneous nucleation and spherulites growth. The morphology and average diameter of spherulites of s‐PDLA‐PLLA with various GNS contents were observed in isothermal crystallization processes by polarized optical microscopy. Spherulite growth rates of samples were evaluated by using combined isothermal and nonisothermal procedures and analyzed by the secondary nucleation theory. The results evidenced that the GNS has acceleration effects on the crystallization of s‐PDLA‐PLLA with good nucleation ability in the s‐PDLA‐PLLA material.     

Achieving highly crystalline rate and crystallinity in Poly(l-lactide) via in-situ melting reaction with diisocyanate and benzohydrazine to form nucleating agents

The drawback of the application for poly(_l-lactide) (PLLA) is the low crystalline rate and crystallinity obtaining via normal processing methods. Modifying crystallization of PLLA has been found to be an efficient way to improve its mechanical and heat resistance properties. In this wok, 4, 4′-diphenylmethane diisocyanate (M) and benzohydrazine (P) were employed into PLLA melt to in-situ form nucleating agents. The in-situ melting reaction was confirmed by a nuclear magnetic resonance spectroscopy. The crystallization behavior and crystalline morphology were investigated by a differential scanning calorimetry, a polarized optical microscopy and a field emission scanning electron microscope. The crystalline rate of PLLA was abruptly enhanced by adding (M+P) and melting reaction with PLLA. The crystallization half-time of PLLA dramatically decreased from 42.0 to 1.1 min at 130 °C by the in-situ formation of nucleating agents. The crystallinity of PLLA increased from 10.3 to 42.1 by adding 0.25% (M+P) and melting reaction for 8 min. Furthermore, the size of PLLA crystals was dramatically reduced because of the nucleating effect. Accompanied with improvement on crystallinity, the Vicat softening temperature of PLLA shifted from 57.4 °C to 93.7 °C by the in-situ reaction with 6.00% (M+P), and indicating heat resistance enhancement.     

Regioselective O-acylation of myo-inositol 1,3,5-orthoesters: dependence of regioselectivity on the stoichiometry of the base

A metal mediated unusual 1-3 acyl migration from C4-O to C2-OH of myo-inositol 1,3,5-orthoformate was observed during the alkylation of racemic 4-O-benzoyl-myo-inositol 1,3,5-orthoformate. This has been exploited for the selective esterification of either the C4(6)-OH or the C2-OH of myo-inositol by varying the amount of the base used. While the use of 1 equiv of the base (sodium hydride or potassium tert-butoxide) for the acylation of myo-inositol orthoesters gives the corresponding C4-ester exclusively, the use of two or more equivalents of base for the same reaction gives the C2-ester exclusively. The relatively higher stability of the alkoxide of racemic 2-O-acyl-myo-inositol 1,3,5-orthoester as compared to the alkoxide of 4-O-acyl-myo-inositol 1,3,5-orthoester is suggested to be responsible for the observed isomerization.     

Thermal epimerization of inositol 1,3-benzylidene acetals in the molten state

1,3-O-Benzylidene-2,4,5,6-tetra-O-substituted-myo-inositol derivatives obtained by the DIBAL-H reduction of the corresponding myo-inositol 1,3,5-orthobenzoate derivatives undergo epimerization at the acetal carbon on heating, in the molten state, just above their melting point. The same epimerization reaction does not proceed either in the crystalline state or in solution. DFT calculations suggest that the epimeric acetal obtained by this thermal process is relatively more stable than the starting acetal. Either of these acetals could not be obtained by the reaction of the corresponding inositol derived diol with benzaldehyde. These observations constitute a novel reaction solely in the molten state, which are rarely encountered in the literature. X-ray crystal structures of the epimeric acetals as well as their radical deoxygenation reaction are also reported.     

Crystallization and melting behavior of poly(ethylene oxide)/poly(n-butyl methacrylate) blends

The phase diagram, crystallization and melting behavior of poly(ethylene oxide) (PEO)/poly(n-butyl methacrylate) (PnBMA) blends have been investigated using differential scanning calorimetry and optical microscopy. The results show that the blends are miscible up to 85 °C and show an lower critical solution temperature-type demixing at a higher temperature. The isothermal crystallization studies of the blends indicate a reduction in the overall rate of crystallization. Analysis of isothermal crystallization data by means of Avrami equation leads to average values of the Avrami index of 2.5 for pure PEO and 3.0 for the different blend compositions. The melting behavior of the blends reveals double endotherms, which is ascribed to both secondary crystallization and recrystallization. The melting point depression study yielded χ₁₂=0, indicating a relatively low interaction strength.     

Stable axial-rich chair conformer of myo-inositol derivatives due to introduction of two adjacent bulky silyl protections

The ring-conformational change of myo-inositol derivatives by introducing two tert-butyldimethylsilyl, triisopropylsilyl, or tert-butyldiphenylsilyl groups into the 1,2-trans hydroxy groups--3,4- and 4,5-positions--were investigated. The cyclohexane cores of the 4,5-bis-O-silylated derivatives with tert-butyldiphenylsilyl or triisopropylsilyl groups were present in the axial-rich chair form.     

Composition analysis of positional isomers of phosphatidylinositol by high-performance liquid chromatography

An HPLC-based method has been developed for composition analysis of six positional isomers of phosphatidylinositol (PI), of which the phosphatidyl group was connected to different positions of the myo-inositol moiety. The method employed a combination of two types of HPLC analyses. One was direct separation of the six PI isomers into four peaks of 1(3)-PI, 2-PI, 4(6)-PI and 5-PI on a normal-phase silica gel column. The second method was for the separations of 1-PI from 3-PI and 4-PI from 6-PI, which were not separable on the normal-phase column. This method involved conversion of PI isomers into pentakis-(R)-1-phenylethylcarbamate (PEC) derivatives, which were separated on a reversed-phase column. Using the established method, positional specificity of several engineered phospholipases D in enzymatic synthesis of PI from myo-inositol and phosphatidylcholine was investigated. This was performed by analyzing the isomeric composition of PIs synthesized by the mutant enzymes. Among five mutant enzymes tested, two showed strong specificity to 1-OH, one showed moderate preference to 1-OH, one preferred 3-OH, and one showed broad specificity towards 1-, 3-, 4- and 6-OH.     

An unusual twist conformation of 2-O-methyl-1,3,4,5-tetrakis-O-tert-butyldiphenylsilyl-myo-inositol

The ring conformation of 2-O-methyl-1,3,4,5-tetrakis-O-tert-butyldiphenylsilyl-myo-inositol was in a twist form both in solid state and in solution. This is the first observation of a stable twist conformer induced by the introduction of bulky silyl protecting groups.