Hybrid structures made of metal nanoparticles with liquid crystalline coating attract considerable attention due to their conspicuous self-assembly and potential synergistic properties. Here we report on a new structural parameter that can be used to control the formation of hybrid gold nanoparticles superlattice. A series of Au nanoclusters covered with mixed monolayers of alkyl and liquid-crystalline ligands were obtained. For the first time in such systems the lengths of both alkyl ligands and mercapto-functionalized alkyl spacers of the promesogenic molecules were varied. The physicochemical properties of the obtained materials were investigated by different instrumental techniques, such as X-ray photoelectron spectroscopy (XPS), small-angle X-ray diffraction (SAXRD), and transmission electron microscopy (TEM). Interestingly, the applied variations of the grafting layer composition enabled the formation of 1D (lamellar) and 3D long-range ordered structures with systematically changing thermal stability range. Such behavior is explained based on the structural parameters of the hybrid nanoparticles, namely the separation of the cores and ligand flexibility. This work gives some new insights into the nanoparticle self-assembly subject and points out the critical parameters controlling the degree of order within the self-assembled superstructures.

A two-step chemical process for controlled degradation of escin, affording a mixture of olean-12-ene sapogenins, was elaborated and scaled up. The main component of the mixture—protoescigenin—was isolated and purified, in the form of its corresponding monohydrate, without resource to chromatographic methods. This material was further converted into the high purity 3,24;16,22-di-O,O-isopropylidene derivative in a validated large scale laboratory process.

Critical survey of a selected class of pentacyclic triterpenes -the oleanane family, is presented based on current literature in order to underline their value for medicinal chemistry and drug development potential. Oleanenes may be considered as a renewable resource of valuable research materials which are structurally diverse, inherently biocompatible and have built-in affinity for many categories of functional proteins. Although availability of particular compounds from natural sources may be very low, synthetic methods elaborated by generations of chemists, secure a way to obtaining desirable structures from commercial starting materials.

The Parkes Weber syndrome (PWS), first described in 1907 [1], is characterized by triad of arteriovenous fistulas (AVF), varicose veins and bone and soft tissue hypertrophy leading to limb enlargement. The symptoms of PWS are congenital and present at birth. Vascular anomalies usually affect a limb, most commonly a leg, and less often a trunk. Capillary malformations, forming geographic patterns, are typically located on lateral side of the limb, buttocks or trunk. The appearance of varicose veins and dilated superficial veins in older age is triggered by arteriovenous shunt, venous hypertension and insufficiency of the deep venous system. The enlargement of a limb is present at birth, and the axial overgrowth can enlarge in postnatal period [2,3]. Cases of shortened lower extremity and pelvis malformations have also been described [4]. Arteriovenous leak may also lead to cardiac system failure or to limb ischemia. Not surprisingly, PWS, similarly to other vascular malformations, significantly reduces the quality of life of the affected patients [5].The treatment of patients with PWS is mainly symptomatic. Compression therapy is used to reduce symptoms of chronic venous insufficiency and lymphatic edema. In selected cases invasive procedures are performed. Surgical treatment is difficult and may require several intravascular procedures, such as embolization, sclerotherapy or classic open operations involving arteriovenous fistula ligation. In severe cases of ischemic extremities amputation is the only therapy. Therefore, there is an ever-existing need to develop a safe and effective pharmacological therapy for PWS patients.For the purpose of the study we have established the first animal model reproducing complex manifestations of PWS and applicable for research on etiology, treatment and prevention of the disease. The model mimics major clinical features characteristic for the human PWS: venous hypertension and dilatation, varicose veins formation, and the limb hypertrophy [6] [7].Cellular biology tools were applied to examine protective effect of ca. 30 new semi-synthetic compounds derived from the main aglycone of escin saponins, on the vascular endothelium under inflammatory conditions. The in vitro tests evaluated i.a. cell proliferation, migration, endothelial monolayer permeability, and the effect on NFκB signal transduction. One paricular molecule (1), obtained in 5 steps as illustrated on the Scheme below, showing promising biological characteristics and favorable physicochemical properties has been selected for in vivo studies [8]. The obtained results confirmed valuable pharmacological properties of the tested compound as all the animals treated with the selected compound showed significantly reduced symptoms of PWS as compared to untreated control. Furthermore, we believe that the molecule should be considered as a promising candidate for the prevention and treatment of other, more common vascular disorders.PeerJ PrePrints | https://doi.org/10.7287/peerj.preprints.1598v1 | CC-BY 4.0 Open Access | rec:

Abstract:The preparation of stable amorphous pemetrexed disodium of pharmaceutical purity as well as the process optimization for the preparation of the hemipentahydrate form of pemetrexed disodium are described. Analytical methods for the polymorphic and chemical purity studies of pemetrexed disodium and pemetrexed diacid forms were developed. The physicochemical properties of the amorphous and hydrate forms of pemetrexed disodium, as well as new forms of pemetrexed diacid (a key synthetic intermediate) were studied by thermal analysis and powder X-ray diffraction. High-performance liquid chromatography and gas chromatography methods were used for the chemical purity and residual solvents determination. In order to study the polymorphic and chemical stability of the amorphous and hemipentahydrate forms, a hygroscopicity test (25 °C, 80% RH) was performed. Powder diffraction and high-performance liquid chromatography analyses revealed that the amorphous character and high chemical purity were preserved after the hygroscopicity test. The hemipentahydrate form transformed completely to the heptahydrate form of pemetrexed disodium. Both pemetrexed disodium forms were produced with high efficiency and pharmaceutical purity in a small commercial scale. Amorphous pemetrexed disodium was selected for further pharmaceutical development. Two new polymorphs (forms 1 and 2) of pemetrexed diacid were used for the preparation of high purity amorphous pemetrexed disodium.

Protoescigenin, the main aglycone of horse chestnut saponin mixture known as escin, was selected as substrate for exploratory chemistry towards selective protection, followed by propargyl ether formation and subsequent condensation with azido-monosaccharides, to obtain novel triazole linked conjugates of the triterpene.

No abstract

The Parkes Weber syndrome (PWS), first described in 1907, is characterized by triad of arteriovenous fistulas (AVF), varicose veins and bone and soft tissue hypertrophy leading to limb enlargement. The symptoms of PWS are congenital and present at birth. Vascular anomalies usually affect a limb, most commonly a leg, and less often a trunk. Capillary malformations, forming geographic patterns, are typically located on lateral side of the limb, buttocks or trunk. The appearance of varicose veins and dilated superficial veins in older age is triggered by arteriovenous shunt, venous hypertension and insufficiency of the deep venous system. The enlargement of a limb is present at birth, and the axial overgrowth can enlarge in postnatal period. Cases of shortened lower extremity and pelvis malformations have also been described. Arteriovenous leak may also lead to cardiac system failure or to limb ischemia. Not surprisingly, PWS, similarly to other vascular malformations, significantly reduces the quality of life of the affected patients. The treatment of patients with PWS is mainly symptomatic. Compression therapy is used to reduce symptoms of chronic venous insufficiency and lymphatic edema. In selected cases invasive procedures are performed. Surgical treatment is difficult and may require several intravascular proce-dures, such as embolization, sclerotherapy or classic open operations involving arteriovenous fistula ligation. In severe cases of ischemic extremities amputation is the only therapy. Therefore, there is an ever-existing need to develop a safe and effective pharmacological therapy for PWS patients. For the purpose of the study we have established the first animal model reproducing complex manifestations of PWS and applicable for research on etiology, treatment and prevention of the disease. The model mimics major clinical features characteristic for the human PWS: venous hypertension and dilatation, varicose veins formation, and the limb hypertrophy. Cellular biology tools were applied to examine protective effect of ca. 30 new semi-synthetic compounds derived from the main aglycone of escin saponins, on the vascular endothelium under inflammatory conditions. The in vitro tests evaluated i.a. cell proliferation, migration, endothelial monolayer permeability, and the effect on NFκB signal transduction. One paricular molecule (1), obtained in 5 steps as illustrated on the Scheme below, showing promising biological characteristics and favorable physicochemical properties has been selected for in vivo studies. The obtained results confirmed valuable pharmacological properties of the tested compound as all the animals treated with the selected compound showed signifi-cantly reduced symptoms of PWS as compared to untreated control. Furthermore, we believe that the molecule should be considered as a promising candidate for the prevention and treatment of other, more common vascular disorders.