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The crystalline packing and the phase structure of a long-chain aliphatic polyester, (O(CH2)22OOCCH2CH2CO)n, PE22,4, have been studied in molecular detail by small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD) experiments as well as various solid-state nuclear magnetic resonance (NMR) methods, in particular two-dimensional double-quantum spectroscopy (DOQSY) NMR. The volume crystallinity is 73 ± 3% according to quantitative 13C NMR and SAXS analyses. The DOQSY NMR spectra show signal characteristic of trans ester groups incorporated into straight poly(methylene) chains, as expected on the basis of WAXD. DOQSY spectra of singly 13COO-labeled diesters prove close proximity of ester groups in neighboring chains, confirming the ester layering deduced from SAXS, with three diester layers per crystallite. SAXS shows a 37° chain tilt with respect to the diester layers and crystallite surface, and the DOQSY NMR spectra confirm the resulting significant displacement of ester groups along neighboring chains. The data suggest a 22tilting of the chain axes. NMR detects no significant disorder along the chain axes; this suggests that the disappearance of (h, k, l≠ 0) reflections in WAXD is due to the small crystallite thickness, which is 5.6 ± 0.5 nm according to SAXS. The DOQSY NMR patterns show that the planes of the chains are far from the perpendicular relative orientation found in orthorhombic polyethylene, constraining the angle between the (normals to the) O−CO ester planes to 55° ± 20°. DOQSY NMR also indicates that ∼1/3 of the COO groups directly at the crystalline−amorphous interface are disordered. The chain loops in the amorphous phase contain only 6% of the esters and thus mostly consist of the C22polymethylene section of one C26repeat unit. The C22loops connect ∼71% of the ends of crystalline stems, while 9% are terminated by chain ends and 20% are connected to a loose loop or tie molecule. NMR relaxation measurements confirm that, in spite of the relatively small fraction of ester groups among the poly(methylene) chains, they strongly suppress the fast 180° chain flips observed in polyethylene crystallites. [ABSTRACT FROM AUTHOR]

A new process, PMOFSA, is described here, that opens the way for the one-pot straightforward and versatile manufacture of polymer-MOF nanoparticles in water. It can be expected that this study will not only expand the scope of in situ preparation of polymer-MOF nano-objects but also inspire researchers in the field to prepare a new generation of polymer-MOF hybrid materials.

Hypothesis: We describe the possibility of using the same block copolymer carriers prepared by PISA for in situ drug encapsulation or drug conjugation., Experiments: Block copolymers containing poly((ethylene glycol) methacrylate)-co-poly(pentafluorophenyl methacrylate)-b-poly(hydroxypropyl methacrylate) (P((PEGMA-co-PFBMA)-b-PHPMA)) were synthesized at 10 wt% using PISA. The first approach involved in situ Doxorubicin (DOX) loading during PISA, while the second exhibited surface functionalization of PISA-made vesicles with dual drug therapies, N-acetyl cysteine (NAC) and DOX using para-fluoro-thiol reaction (PFTR) and carbodiimide chemistry, respectively. Cytotoxicity, cell uptake, and cell apoptosis were assessed on MDA-MB-231 cell lines., Findings: P((PEGMA-co-PFBMA)-b-PHPMA) nanocarriers were prepared, showing size and shape transformations from spheres, cylinders to raspberry-forming vesicles. DOX was readily loaded into NPs during PISA with relatively high encapsulation efficiency of 70 %, whereas the plain PISA-made vesicles could be functionalized with NAC and DOX at high yields. DOX-free NPs showed biocompatibility, whilst DOX-conjugated NPs imparted a concentration-dependent cytotoxicity, as well as an enhanced cell uptake compared to free DOX. The results demonstrated that the same PISA-derived self-assemblies enabled either in situ drug encapsulation, or post-polymerization surface engineering with useful functionalities upon tuning the macro-CTA block, thus holding promises for future drug delivery and biomedical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Stimuli-responsive amphiphilic block copolymers have emerged as promising nanocarriers for enhancing site-specific and on-demand drug release in response to a range of stimuli such as pH, the presence of redox agents, and temperature. The formulation of amphiphilic block copolymers into polymeric drug-loaded nanoparticles is typically achieved by various methods (e.g. oil-in-water emulsion solvent evaporation, solid dispersion, microphase separation, dialysis or microfluidic separation). Despite much progress that has been made, there remain many challenges to overcome to produce reliable polymeric systems. The main drawbacks of the above methods are that they produce very low solid contents (<1 wt%) and involve multiple-step procedures, thus limiting their scope. Recently, a new self-assembly methodology, polymerisation-induced self-assembly (PISA), has shown great promise in the production of polymer-derived particles using a straightforward one-pot approach, whilst facilitating high yield, scalability, and cost-effectiveness for pharmaceutical industry protocols. We therefore focus this review primarily on the most recent studies involved in the design and preparation of PISA-generated nano-objects which are responsive to specific stimuli, thus providing insight into how PISA may become an effective formulation strategy for the preparation of precisely tailored drug delivery systems and biomaterials, while some of the current challenges and limitations are also critically discussed.

In this study, a novel anticancer reagent based on polyplexes nanoparticles was developed. These nanoparticles are obtained by mixing negatively charged polyelectrolytes with the antitumour cationically-charged pseudopeptide N6L. Using two in vivo experimental tumor pancreatic models based upon PANC-1 and mPDAC cells, we found that the antitumour activity of N6L is significantly raised via its incorporation in polyplexed nanoparticles. Study of the mechanism of action using affinity isolation and si-RNA experiments indicated that N6L-polyplexes are internalized through their interaction with nucleolin. In addition, using a very aggressive model of pancreatic cancer in which gemcitabine, a standard of care for this type of cancer, has a weak effect on tumour growth, we observed that N6L-polyplexes administration has a stronger efficacy than gemcitabine. Biodistribution studies carried out in tumour-bearing mice indicated that N6L-polyplexes localises in tumour tissue, in agreement with its antitumour effect. These results support the idea that N6L nanoparticles could develop into a promising strategy for the treatment of cancer, especially hard-to-treat pancreatic cancers., Competing Interests: CONFLICTS OF INTEREST A potential conflicts of interests could exist related to this study, since José Courty is a co-author of a existing patent on the used of N6L in the treatment of cancer.

We study the self-assembly of a new family of amphiphilic liquid crystal (LC) copolymers synthesized by the anionic ring-opening polymerization of a new cholesterol-based LC monomer, 4-(cholesteryl)butyl ethyl cyclopropane-1,1-dicarboxylate. Using the t-BuP(4) phosphazene base and thiophenol or a poly(ethylene glycol) (PEG) functionalized with thiol group to generate in situ the initiator during the polymerization, LC homopolymer and amphiphilic copolymers with narrow molecular weight distributions were obtained. The self-assemblies of the LC monomer, homopolymer, and block copolymers in bulk and in solution were studied by small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and transmission electron microscopy (TEM). All polymers exhibit in bulk an interdigitated smectic A (SmA(d)) phase with a lamellar period of 4.6 nm. The amphiphilic copolymers self-organize in solution into vesicles with wavy membrane and nanoribbons with twisted and folded structures, depending on concentration and size of LC hydrophobic block. These new morphologies will help the comprehension of the fascinating organization of thermotropic mesophase in lyotropic structures.

The successful activation observed when using Bu(t) P(4) phosphazene base and thiophenol or bisthiols for the anionic ring opening polymerization (ROP) of di-n-propyl cyclopropane-1,1-dicarboxylate is described. Well-defined monofunctional or difunctional polymers with a very narrow molecular weight distribution were obtained through a living process. Quantitative end-capping of the propagating malonate carbanion was accessible by using either an electrophilic reagent such as allyl bromide or a strong acid such as HCl. Kinetics studies demonstrated a much higher reactivity compared to the conventional route using alkali metal thiophenolates., (Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of robust methodologies to control the solid-state structure of polymeric materials by appropriate design of the macromolecular architecture has a crucial impact on the mechanical properties of these materials. Here, we demonstrate the feasibility of controlling chain folding of polymers by steric interactions only, in contrast to previous attempts aimed at engineering polymer crystallization through hydrogen bonding. In a linear synthetic macromolecule similar to polyethylene, we encoded structural instructions that are translated during a crystallization process to generate a unique, semi-crystalline morphology with structure-controlled crystal thickness of approximately 5 nm that remains constant over a wide temperature range. The molecular code consists of a linear backbone alternating crystallizable, long alkyl sequences of monodisperse sizes separated by short spacers containing side-chains and acting as stops and fold-controlling units. This simple strategy could be used to produce advanced polymeric materials with fine control of the crystalline and amorphous regions.

Several mono- and bisindole quaternary alkaloids isolated from the stem bark of Strychnos guianensis have recently been shown to be effective blockers of neuromuscular transmission in mice. In this study, we used a human clonal cell line (TE671) expressing muscle-type nicotinic acetylcholine receptors. The agonist carbamylcholine activated a receptor-mediated (86)Rb(+) efflux and this activation was antagonized by the indole alkaloids, the most active being bisindole bisquaternary compounds. The most effective antagonist, guiachrysine, had an IC(50) around 0.43 microM in the presence of 0.5 mM carbamylcholine, compared to 0.16 microM for d-tubocurarine, the most potent curarizing alkaloid. Guiaflavine and 5',6'-dehydroguiaflavine were slightly less effective. Monoindole compounds were 10 to 100 times less potent than bisindole alkaloids. Kinetic analysis showed that the inhibition of the carbamylcholine-dependent (86)Rb(+) efflux by guiaflavine was of mixed competitive and uncompetitive type. The competitive component (K(I)=0.21 microM) is presumably due to binding at the acetylcholine site, while the uncompetitive component (K'(I)=0.92 microM) may be due to open channel block.

A model system for the characterization of molecular recognition events in molecularly imprinted polymers (MIPs) is presented. The use of a biologically inspired, three-point hydrogen-bonding motif and a thin film polymeric matrix allows for pre- and post-polymerization binding properties to be characterized by infrared spectroscopy. A method to determine binding constants was developed and utilized before and after cross-linking. These values showed a 10-fold decrease in binding after polymerization, which was attributed to an increase in molecular confinement after polymerization and a change in the local structural environment of the binding cavity. Transport of the guest molecule was shown to be reversible.

Two new quaternary indole alkaloids 5',6'-dehydroguiachrysine (1) and 5',6'-dehydroguiaflavine (2) were isolated from Strychnos guianensis stem bark. Their structures were determined by analysis of spectral data. Their inhibitory effects on neuromuscular transmission are also reported and compared to that of other quaternary alkaloids.

The enzymatic glucose cleavage of palicoside revealed the biosynthetic pathway to akagerine, whereas the conversion of dolichantoside led to a new quaternary heteroyohimbine alkaloid named N(b)-methyl-21-beta-hydroxy-mayumbine. The hypothetical models of reactions occurring after the conversion of both substrates are proposed. Dolichantoside and palicoside, as well as Strychnos mellodora stem bark crude ethanol extract, exhibit significant antimycotic activity against human pathogens in presence of specific glucosidase.

A reinvestigation of Strychnos icaja roots has resulted in the isolation of two tertiary quasi-symmetric bisindole alkaloids named strychnogucines A (1) and B (2). Their structures were identified by means of spectroscopic data interpretation. Compound 2 was highly active in vitro and compound 1 moderately active against four strains of Plasmodium falciparum. Strychnogucine B (2) was more active against a chloroquine-resistant strain than against a chloroquine-sensitive one (best CI(50), 80 nM against the W2 strain). In addition, this compound showed a selective antiplasmodial activity with 25-180 times greater toxicity toward P. falciparum, relative to cultured human cancer cells (KB) or human fibroblasts (WI38).

Two new quaternary alkaloids, 9-methoxy-Nb-methylgeissoschizol and guiachrysine together with the known compounds C-alkaloid O, fluorocurine, mavacurine, macusine B and C-profluorocurine, were isolated from Strychnos guianensis stembark. The structures of the compounds were elucidated on the basis of spectroscopic studies.

Reinvestigation of Strychnos icaja Baillon resulted in the isolation of vomicine, isostrychnine and of three new sungucine derivatives, named isosungucine (8), 18-hydroxy-sungucine (9) and 18-hydroxy-isosungucine (10). They were identified by detailed spectroscopic methods. The complete 1H- and 13C-NMR study of sungucine was also realized. Some of these compounds were highly active against Plasmodium falciparum in vitro and more particularly against the chloroquine-resistant strain. Compound 10 showed a selective antiplasmodial activity, with > 100-fold greater toxicity towards Plasmodium falciparum, relative to cultured human cancer cells (KB and HeLa lines) or fibroblasts (WI38).

A reinvestigation of Strychnos guianensis resulted in the isolation of a colored quaternary bisindole alkaloid from the stem bark. The structure of this new substance, guiaflavine (1), was defined by detailed spectroscopic methods and comparison with model compounds.

Reinvestigation of Strychnos usambarensis Gilg resulted in the isolation of a tertiary phenolic bisindole alkaloid, 10'-hydroxyusambarensine (1), which was identified by detailed spectroscopic methods. Compound 1 was moderately active against two strains of Plasmodium falciparum in vitro.

The reinvestigation of Strychnos nux-vomica resulted in the isolation of a colored monoquaternary bisindole alkaloid from the roots. The structure of this new orange substance, strychnochrysine (1), was defined by detailed spectroscopic methods.