Dynamic Titania Nanotube Surface Achieves UV-Triggered Charge Reversal and Enhances Cell Differentiation.

Stimuli-responsive biomaterials supply a promising solution to adapt to the complex physiological environment for different biomedical applications. In this study, a dynamic UV-triggered pH-responsive biosurface was constructed on titania nanotubes (TNTs) by loading photoacid generators, diphenyliodonium chloride, into the nanotubes, and grafting 2,3-dimethyl maleic anhydride (DMMA)-modified hyperbranched poly(l-lysine) (HBPLL) onto the surface. The local acidity was dramatically enhanced by UV irradiation for only 30 s, leading to the dissociation of DMMA and thereby the transformation of surface chemistry from negatively charged caboxyl groups to positively charged amino groups. The TNTs-HBPLL-DMMA substrate could better promote proliferation and spreading of rat bone mesenchymal stem cells (rBMSCs) after UV irradiation. The osteogenic differentiation of rBMSCs was enhanced because of the charge reversal in combination with the titania-based substrates.

A versatile and accessible polymer coating for functionalizable zwitterionic quantum dots with high DNA grafting efficiency.

Efficient and versatile functionalization of poly(anhydride maleic-alt-isobutylene) (PIMA), with economical commercial reagents, results in the one-step/one-day production of a copper-free click chemistry-ready carboxybetaine-like coating for quantum dots (QDs). The QDs are bright and stable in aqueous media and easily grafted with DNA with >95% efficiency.

Polyethylenimine modified with 2,3-dimethylmaleic anhydride potentiates the antitumor efficacy of conventional chemotherapy.

Conventional chemotherapy is a standard care for many cancers at present. However, their severe dose-dependent side effects are the major impediment for successful cancer therapy. Herein nanoparticles were used as a potentiator to enhance the uptake of free chemotherapeutic agents by cancer cells during chemotherapy. A pH-sensitive ß-carboxylate amide group-containing polymer, bPEI-DMA, was obtained by a one-step chemical reaction of commercially available branched polyethyleneimine with 2,3-dimethylmaleic anhydride. The obtained single-macromolecule nanoparticles with a size of 6.4 nm possessed zwitterions and a slight net negative charge at neutral pH, and thereby showed low cytotoxicity. Incubation of MCF-7 cells with bPEI-DMA at tumor acidic pHs led to leakage of lactate dehydrogenase from the cells. Sequential incubation of bPEI-DMA and doxorubicin with MCF-7 cells at tumor acidic pHs caused enhanced uptake of doxorubicin by the cells. These results can be attributed to the tumor pH-triggered positive charge generation on the nanoparticles due to the hydrolysis of the ß-carboxylate amide groups, and subsequently the positive charge caused an increase in cell membrane permeability. Sequential injection of bPEI-DMA and free doxorubicin or free cisplatin into nude mice bearing human tumors markedly inhibited the tumor growth, leading to a ~ 68% decrease in tumor volumes compared to injection of the free drugs alone. Sequential injection of bPEI-DMA and a half dose of free doxorubicin resulted in even greater tumor inhibition but less side effects than injection of a full dose of doxorubicin alone.

A review on various maleic anhydride antimicrobial polymers.

The basic requirement of human beings is better health but the serious health effects and numerous infections caused by rapid growth of harmful pathogens resulting in a large number of deaths and is a significant challenge to modern science. Microbes infecting humans can be stopped in two ways: disinfectants and antimicrobial agents. There is considerable interest from both academics and industry in antimicrobial polymers due to their favorable properties. Maleic anhydride incredibly bears diverse commercial applications due to its versatile chemical structure. Maleic anhydride is an electron-acceptor monomer where the property comes from reactive double bonds and also reactive anhydride groups. This review presents the development of antimicrobial polymers involving maleic anhydride in the macromolecular structure. This article also addresses the applications of antimicrobial polymers with maleic anhydride in numerous sectors.

Total Synthesis of (±)-Phomoidride†D.

Described herein is a synthetic strategy for the total synthesis of (±)-phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.

Protecting group-free radical decarboxylation of bile acids: Synthesis of novel steroidal substituted maleic anhydrides and maleimides and evaluation of their cytotoxicity on C6 rat glioma cells.

We report the first Barton radical decarboxylation of unprotected bile acids via in situ irradiation of their thiohydroxamic esters in the presence of citraconic anhydride and citracoimide, leading to the synthesis a series of steroidal maleic anhydrides and maleimides as novel hybrid bile acids. The cytotoxic activities were evaluated on C6 rat glioma cells.

Self-healing pH-sensitive poly[(methyl vinyl ether)-alt-(maleic acid)]-based supramolecular hydrogels formed by inclusion complexation between cyclodextrin and adamantane.

Self-healing materials are of interest for drug delivery, cell and gene therapy, tissue engineering, and other biomedical applications. In this work, on the base of biocompatible polymer poly(methyl vinyl ether-alt-maleic acid) (P(MVE-alt-MA)), host polymer ß-cyclodextrin-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-ß-CD) and guest polymer adamantane-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-Ad) were first prepared. Then through taking advantage of the traditional host-guest interaction of ß-cyclodextrin and adamantane, a novel self-healing pH-sensitive physical P(MVE-alt-MA)-g-ß-CD/P(MVE-alt-MA)-g-Ad supramolecular hydrogels were obtained after simply mixing the aqueous solution of host polymer and guest polymer. This kind of supramolecular hydrogels not only possess pH-sensitivity, but also possess the ability to repair themselves after being damaged.

Peptide-functionalized ZCIS QDs as fluorescent nanoprobe for targeted HER2-positive breast cancer cells imaging.

In this paper, the synthesis of alloyed CuInZnxS2+x quantum dots (ZCIS QDs), their transfer into aqueous solution via a polymer coating technique, and the use of these nanocrystals to selectively target HER2-positive cells, are reported. By optimizing first the ZnS shell deposition process onto the CuInS2 core, and next the encapsulation of the dots with the amphiphilic poly(maleic anhydride-alt-1-octadecene) (PMAO) polymer, water-dispersible ZCIS QDs were successfully prepared. The nanocrystals with a photoluminescence quantum yield of 35% were purified via centrifugation and ultracentrifugation and high quality nanoparticles with narrow size distributions and surface charges were obtained. After verifying the biocompatibility of PMO-coated ZCIS QDs, we coupled these nanocrystals with the LTVSPWY peptide and demonstrated via MTT assay that both bare and the peptide-linked QDs exhibit low cytotoxicity. The HER2-mediated delivery of the peptide-linked QDs was confirmed by confocal microscopy. This study indicates that as engineered QDs can efficiently be used as fluorescent nanoprobes for selective labelling of HER2-positive SKBR3 cancer cells.

Biosynthetic Study on Antihypercholesterolemic Agent Phomoidride: General Biogenesis of Fungal Dimeric Anhydrides.

To elucidate the general biosynthetic pathway of fungal dimeric anhydrides, a gene cluster for the biosynthesis of the antihy-percholesterolemic agent phomoidride was identified by heterologous expression of candidate genes encoding the highly reducing polyketide synthase, alkylcitrate synthase (ACS), and alkylcitrate dehydratase (ACDH). An in vitro analysis of ACS and ACDH revealed that they give rise to anhydride monomers. Based on the established monomer biosynthesis, we propose a general biogenesis of dimeric anhydrides involving a single donor unit and four acceptor units.

Releasable Conjugation of Polymers to Proteins.

Many synthetic strategies are available for preparing well-defined conjugates of peptides/proteins and polymers. Most reports on this topic involve coupling methoxy poly(ethylene glycol) to therapeutic proteins, a process referred to as PEGylation, to increase their circulation lifetime and reduce their immunogenicity. Unfortunately, the major dissuading dogma of PEGylation is that, in many cases, polymer modification leads to significant (or total) loss of activity/function. One approach that is gaining momentum to address this challenge is to release the native protein from the polymer with time in the body (releasable PEGylation). This contribution will present the state-of-the-art of this rapidly evolving field, with emphasis on the chemistry behind the release of the peptide/protein and the means for altering the rate of release in biological fluids. Linkers discussed include those based on the following: substituted maleic anhydride and succinates, disulfides, 1,6-benzyl-elimination, host-guest interactions, bicin, ß-elimination, biodegradable polymers, E1cb elimination, ß-alanine, photoimmolation, coordination chemistry, zymogen activation, proteolysis, and thioesters.

Anti-HIV activities of precisely defined, semirigid, carboxylated alternating copolymers.

Di-tert-butyl (E)-4,4'-stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. For both the IIIb and BaL HIV-1 strains, the lowest IC50 (0.095 and 0.23 µg/mL, respectively) values were obtained with poly(4,4'-stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA). For JR-CSF and 92UG037, both tier 2 clinical isolates but different clades, DCSti-alt-MA exhibited the lowest IC50 (0.76 and 0.75 µg/mL, respectively). Although DCSti-alt-MA had the lowest IC50 in µg/mL for each strain, the other copolymers had IC50s less than 2-fold higher. Further, these copolymers achieved high selectivity indices (>100) for these clinical isolates. Polymer rigidity, as measured by the statistical segment length, emerged as a key property when comparing anti-HIV activities with those of other polyanions. A speculative illustration was proposed for possible modes of inhibition.

Synthesis and characterization of maleic anhydride esterified corn starch by the dry method.

Maleic anhydride esterified starch was synthesized by a dry method using corn starch as the material and maleic anhydride as the esterifying agent. The esterified starch (ES) was analyzed by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), which confirmed that there was a successful esterification reaction between the maleic anhydride and corn starch. The effects of reaction temperature and time on the degree of substitution of esterified starch were studied, where the results showed that 80 °C of reaction temperature and 3h of reaction time were optimal conditions. The result of XPS testing demonstrated that the esterification reaction led to increase of ester bonds in starch. The scanning electron microscopy (SEM) and laser particle size analyzer results showed that esterification led to roughness on the surface of the starch particle, and the particle size and distribution rate of esterification starch became larger. X-ray diffraction (XRD) analysis demonstrated that esterification reaction did not change the crystalline type of native starch. The differential scanning calorimeter (DSC) and thermo gravimetric analysis (TGA) confirmed that destruction of the crystal structure resulted in improved thermoplasticity of the starch, decreased the gelatinization temperature and increased the thermogravimetric rate of esterification starch.

Synthetic studies on CP-225,917 and CP-263,114: access to advanced tetracyclic systems by intramolecular conjugate displacement and [2,3]-Wittig rearrangement.

An advanced intermediate related to the structures of CP-225,917 and CP-263,114 was constructed by a sequence based on the use of Grob-like fragmentation, intramolecular conjugate displacement, and [2,3]-Wittig rearrangement. A variant of the [2,3]-Wittig rearrangement was developed.

Preparation and characterization of bagasse/HDPE composites using multi-walled carbon nanotubes.

This article presents the preparation and characterization of bagasse/high density polyethylene (HDPE) composites. The effects of multi-walled carbon nanotubes (MWCNTs), as reinforcing agent, on the mechanical and physical properties were also investigated. In order to increase the interphase adhesion, maleic anhydride grafted polyethylene (MAPE) was added as a coupling agent to all the composites studied. In the sample preparation, MWCNTs and MAPE contents were used as variable factors. The morphology of the specimens was characterized using scanning electron microscopy (SEM) technique. The results of strength measurement indicated that when 1.5 wt% MWCNTs were added, tensile and flexural properties reached their maximum values. At high level of MWCNTs loading (3 or 4 wt%), increased population of MWCNTs lead to agglomeration and stress transfer gets blocked. The addition of MWCNTs filler slightly decreased the impact strength of composites. Both mechanical and physical properties were improved when 4 wt% MAPE was applied. SEM micrographs also showed that the surface roughness improved with increasing MAPE loading from 0 to 4 wt%. The improvement of physicomechanical properties of composites confirmed that MWCNTs have good reinforcement and the optimum synergistic effect of MWCNTs and MAPE was achieved at the combination of 1.5 and 4 wt%, respectively.

Toward the synthesis of phomoidride D.

An efficient and highly stereoselective approach toward the phomoidride family of natural products is described. The carbocyclic core structure was assembled using a tandem phenolic oxidation/Diels-Alder cycloaddition and a tandem 5-exo-trig/5-exo-trig radical cyclization to deliver an isotwistane intermediate that, upon a late-stage xanthate-initiated Grob fragmentation, furnishes the requisite bicyclo[4.3.1]decene.

Controlled release of doxorubicin loaded within magnetic thermo-responsive nanocarriers under magnetic and thermal actuation in a microfluidic channel.

We report a procedure to grow thermo-responsive polymer shells at the surface of magnetic nanocarriers made of multiple iron oxide superparamagnetic nanoparticles embedded in poly(maleic anhydride-alt-1-ocatadecene) polymer nanobeads. Depending on the comonomers and on their relative composition, tunable phase transition temperatures in the range between 26 and 47 °C under physiological conditions could be achieved. Using a suitable microfluidic platform combining magnetic nanostructures and channels mimicking capillaries of the circulatory system, we demonstrate that thermo-responsive nanobeads are suitable for localized drug delivery with combined thermal and magnetic activation. Below the critical temperature nanobeads are stable in suspension, retain their cargo, and cannot be easily trapped by magnetic fields. Increasing the temperature above the critical temperature causes the aggregation of nanobeads, forming clusters with a magnetic moment high enough to permit their capture by suitable magnetic gradients in close proximity to the targeted zone. At the same time the polymer swelling activates drug release, with characteristic times on the order of one hour for flow rates of the same order as those of blood in capillaries.

Wharton-fragmentation-based approach to the carbocyclic core of the phomoidrides.

The carbocyclic core of the phomoidrides has been synthesized efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and a late-stage Wharton fragmentation of a densely functionalized isotwistane skeleton.

Bioengineering functional copolymers. XXI. Synthesis of a novel end carboxyl-trithiocarbonate functionalized poly(maleic anhydride) and its interaction with cancer cells.

A novel carboxyl-trithiocarbonate functionalized polymer with a highly selective antitumor activity was synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization of maleic anhydride (MA) with benzoyl peroxide as an initiator and S-1-dodecyl-S-(α,α'-dimethyl-α"-acetic acid)trithiocarbonate as a RAFT agent with the aim to design and synthesize an effective anticancer agent with minimum side effects. The structure, molecular weights and composition of synthesized polymers were investigated by (1)H ((13)C) NMR, MALDI-TOF-MS and GPC analyzes. It was demonstrated that RAFT polymerization of MA was accompanied by a partially controlled decarboxylation of anhydride units and the formation of conjugated double bond fragments in backbone macromolecular chains. The mechanism of interaction of pristine RAFT agent and PMA-RAFT polymer with cancer (HeLa human cervix carcinoma) and normal (L929 Fibroblast) cells was investigated by using a combination of chemical, biochemical, statistical, spectroscopic (SEM and fluorescence inverted microscope) and real-time analysis (RTCA) methods. PMA-RAFT exhibited higher and selective cytotoxicity, apoptotic and necrotic effects toward HeLa cells at relatively low concentrations (around 7.5-75 µg mL(-1), IC(50) = 11.183 µg mL(-1)) and toward Fibroblast cells at high concentrations (IC(50) > 100 µg mL(-1)). The observed highly selective antitumor activity render PMA-RAFT polymers as promising candidates for the utilization in cancer chemotherapy.

A colorimetric proton sponge.

1,8-Bis(dimethylamino)naphthalene ("Proton Sponge") and bromomaleic anhydride react quickly at room temperature, generating 3-(4,5-bis(dimethylamino)napthalen-1-yl)furan-2,5-dione (4-maleicanhydridoproton sponge or "MAPS"). MAPS is a deep purple solid that exhibits positive solvatochromism in solution. It is a weaker base than Proton Sponge. When protonated in solution, MAPS loses its color, but the color change can be reversed by deprotonation with a stronger base. MAPS thus acts as a colorimetric version of a proton sponge.