Chitosan Monomer Research Articles

The epoxy-tannic-modified crosslinked chitosan matrix with a selectively adsorptive activity towards charged proteins

Chitosan-based matrices have been proposed for the design of absorbents with target-selective activity, because they are easily modifiable, are cationic polyelectrolytes, and can be regenerated. In this study, chitosan monomers were folded into special three-dimensional structures by crosslinking them with epichlorohydrin and tannic acid. The introduction of active and charged groups such as epoxy and phenolic hydroxyl and synergistic effects among these groups produce chitosan matrices with differing abilities to adsorb proteins such as bovine serum albumin, ovalbumin, myoglobin, and lysozyme in an acidic environment. The adsorptive efficiency of proteins was evaluated via liquid chromatography. Bovine serum albumin and myoglobin were progressively adsorbed while ovalbumin was bound due to strong affinity and lysozyme was saturated in the initial stage. The protein selectivity was primarily dependent on molecular weight, molecular size, isoelectric point, and coulombic attraction. The study illustrated varying effectiveness of charged protein adsorption as well as different adsorption profiles.

Density functional theory study on the interaction of chitosan monomer with TiO2, SiO2 and carbon nanotubes

In the present work, theoretical studies based on density functional theory (DFT) have performed to comprehend the interaction between the Chitosan (CS) monomer and three types of nanotubes, namely TiO2 nanotube (TiO2NT), SiO2 nanotube (SiO2NT) and Carbon nanotube (CNT). First, the geometry of nanotubes and CS monomer and various configuration of their composites have optimized. Subsequently, the adsorption energy and equilibrium distance between CS monomer and nanotubes for the energetically most favorable Structure have calculated by the DFT method. The achieved results indicate that CS monomer has a tendency to be chemisorbed onto the surface of TiO2NT (Ei=−1.41eV) while the type of interactions for the SiO2NT (Ei=−0.24eV) and CNT (Ei=−0.22eV) systems are noncovalent and the CS monomer physisorbed onto the surface of these nanotubes. It was found that the interaction of CS with TiO2NT due to the shorter equilibrium distance and greater adsorption energy is stronger than other nanotubes. We have also investigated the influence of TiO2NT diameter on the adsorption feature, and the results revealed that the adsorption energy between CS and TiO2NTs reduces by increasing TiO2NTs diameter. Moreover, the electronic density of state (DOS) of the energetically most favorable composites was analyzed. The findings of the current work would be very beneficial for scientists to explore the potential applications of these nanocomposite materials in biomedical field such as drug delivery and tissue engineering.

Combined Efficacy of an Antimicrobial Cationic Peptide Polymer with Conventional Antibiotics to Combat Multidrug-Resistant Pathogens.

Antibiotic-resistant infections are predicted to kill 10 million people worldwide per year by 2050 and to cost the global economy 100 trillion USD. Novel approaches and alternatives to conventional antibiotics are urgently required to combat antimicrobial resistance. We have synthesized a chitosan-based oligolysine antimicrobial peptide, CSM5-K5 (where CSM denotes chitosan monomer repeat units and K denotes lysine amino acid repeat units), that targets multidrug-resistant (MDR) bacterial species. Here, we show that CSM5-K5 exhibits rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA), MDR Escherichia coli, and vancomycin-resistant Enterococcus faecalis (VRE). Combinatorial therapy of CSM5-K5 with antibiotics to which each organism is otherwise resistant restores sensitivity to the conventional antibiotic. CSM5-K5 alone significantly reduced preformed bacterial biofilm by 2-4 orders of magnitude and, in combination with conventional antibiotics, reduced preformed biofilm by more than 2-3 orders of magnitude at subinhibitory concentrations. Moreover, using a mouse excisional wound infection model, CSM5-K5 treatment reduced bacterial burdens by 1-3 orders of magnitude and acted synergistically with oxacillin, vancomycin, and streptomycin to clear MRSA, VRE, and MDR E.coli, respectively. Importantly, little to no resistance against CSM5-K5 arose for any of the three MDR bacteria during 15 days of serial passage. Furthermore, low level resistance to CSM5-K5 that did arise for MRSA conferred increased susceptibility (collateral sensitivity) to the β-lactam antibiotic oxacillin. This work demonstrates the feasibility and benefits of using this synthetic cationic peptide as an alternative to, or in combination with, traditional antibiotics to treat infections caused by MDR bacteria.

Anti-Hepatoma Activity of A New Selenium-Rich Chitosan from 6-Hydroxy Esterification of Chitosan Copper

This paper presents a technique to produce a selenium-rich chitosan by 6-hydroxy esterification of chitosan copper whose mole ratio of chitosan monomer and Cu is almost 1:1, which is suitable for the fields of food and feed chemistry or fine chemical technology, and belongs to the field of biomedical engineering technology. 6-Selenite chitosan copper will have better application prospect in medicine and make as selenium nutrient supplement in food, feed and agricultural fields, due to its higher selenium content and lower dosage than existing seleno-chitosan. The selenite chitosan copper effect than the common selenate chitosan. Selenite chitosan copper, which contains 10 times more selenium then existing seleno-chitosan or selenate chitosan, can greatly reduce its use and have a better anti-hepatoma effect. Metal ion protected amino group can bind to acid in the process of biological metabolism, and has a good targeting effect on the weak acidic environment of hepatocellular carcinoma tumors. Previous experiments in vitro showed that the IC50 value of selenite chitosan copper inhibiting HepG2 cells was 20.3 mg/L, and the inhibition rate to HepG2 cells was 87% at the concentration of 50 mg/L.

Синтез и физико-химические свойства привитых сополимеров хитозана и акриловых мономеров

Синтез и физико-химические свойства привитых сополимеров хитозана и акриловых мономеров

Understanding the interfacial interactions of bioinspired chitosan-calcite nanocomposites by first principles molecular dynamics simulations and experimental FT-IR spectroscopy

The interfacial structures and bonding mechanism of the adsorption of chitosan monomers (GlcN and GlcNAc) on calcite (104) surface are investigated using first principles molecular dynamics simulations. It is revealed that the strong coordination CaO bonds are formed between five-fold coordinated Ca atoms on calcite surface and O atoms of hydroxyl groups (OH) and acetyl groups of chitosan in the chitosan-calcite nanocomposites, improving the chemical compatibility between organic and inorganic phases at the interface in the natural occurring nacre. Although, the presence of interfacial hydrogen bonds is also confirmed by analyzing the valence electron density difference in terms of induced dipole, the evolution of the equilibrium adsorption geometry is found to be mainly governed interfacial CaO coordination bonds. The amide group (NH2) of chitosan binds with calcite at the interface mainly through the formation of weak hydrogen bond. The predicted interfacial electronic structure can be either conductive (GlcNAc) or insulating (GlcN). The frequencies of the characteristic peaks in the calculated total and partial vibrational densities of states of GlcN/calcite systems are found to be in agreement with the FT-IR spectrum of the experimentally prepared chitosan-calcite nanocomposites, crucially validating the modelling structures and computational methodology employed in current work. Theoretical results strongly indicate that the peculiar adsorption in FT-IR spectrum at 2500 cm−1 is related to the presence of free GlcN molecule due to the hydrolysis of chitosan in aqueous solution.

Chondroprotective action of glucosamine, a chitosan monomer, on the joint health of athletes.

It has been reported that cartilage metabolism (type II collagen degradation) is enhanced in endurance athletes with intense joint loading. Notably, glucosamine, a chitosan monomer, exhibits a chondroprotective action on osteoarthritis by inhibiting type II collagen degradation. Here, we evaluated the action of glucosamine on cartilage metabolism in soccer and rugby players with intense joint loading. In soccer and rugby players, the urine level of type II collagen degradation maker (CTX-II) was significantly increased compared with non-athlete control, indicating that cartilage metabolism is enhanced in these athletes. In contrast, the urine level of type II collagen synthesis maker (CPII) was almost the same as in non-athletes. These findings suggest that type II collagen degradation is relatively increased compared with type II collagen synthesis in these athletes. Interestingly, the administration of glucosamine-containing diet significantly decreased the CTX-II level but not the CPII level in these athletes. These observations suggest that cartilage metabolism (type II collagen degradation) is increased in endurance athletes (such as soccer and rugby players), and glucosamine demonstrates a chondroprotective action on these athletes by preventing type II collagen degradation but maintaining type II collagen synthesis.

Computational studies at the density functional theory (DFT) level about the surface functionalization of hexagonal monolayers by chitosan monomer

Theoretical investigations based on density functional theory have been carried out to understand the underlying interactions between the chitosan monomer and several types of hexagonal monolayers consisting of pristine and defected graphene and boron-nitride nanosheets. Based on the obtained results, it was found that the type of the interaction for all the systems is of non-covalent nature and the chitosan monomer physically interacts with the surface of mentioned nanostructures. The interaction strength was evaluated by calculating the adsorption energies for the considered systems and it was found that the adsorption of chitosan monomer accompanies by the release of about −0.67 and −0.66 eV energy for pristine graphene and h-BN monolayer, respectively. The role of structural defect has also been considered by embedding a Stone-Wales defect within the structure of mentioned monolayers and it was found that the introduced defect enhances the interactions between the chitosan monomer and nanostructures. The role of dispersion interactions has also been taken into account and it was found that these long-range interactions play the dominating role in the attachment of chitosan monomer onto the graphene sheet, while having strong contribution together with the electrostatic interactions for the stabilization of chitosan onto the surface of h-BN monolayer. For all the cases, the adsorption of chitosan monomer did not change the inherent electronic properties of the nanostructures based on the results of charge transfer analysis and energy gap calculations. The findings of the present work would be very useful in future investigations to explore the potential applications of these hybrid materials in materials science and bio-related fields.

Targeted Drug Delivery and Treatment of Endoparasites with Biocompatible Particles of pH-Responsive Structure.

Biomaterials conceived for vectorization of bioactives are currently considered for biomedical, biological, and environmental applications. We have produced a pH-sensitive biomaterial composed of natural source alginate and chitosan polysaccharides for application as a drug delivery system via oral administration. The composite particle preparation was in situ monitored by means of isothermal titration calorimetry. The strong interaction established between the macromolecules during particle assembly led to 0.60 alginate/chitosan effective binding sites with an intense exothermic effect and negative enthalpy variation on the order of a thousand kcal/mol. In the presence of model drugs mebendazole and ivermectin, with relatively small and large structures, respectively, mebendazole reduced the amount of chitosan monomers available to interact with alginate by 27%, which was not observed for ivermectin. Nevertheless, a state of intense negative Gibbs energy and large entropic decrease was achieved, providing evidence that formation of particles is thermodynamically driven and favored. Small-angle X-ray scattering provided further evidence of similar surface aspects independent of the presence of drug. The physical responses of the particles to pH variation comprise partial hydration, swelling, and the predominance of positive surface charge in strong acid medium, whereas ionization followed by deprotonation leads to compaction and charge reversal rather than new swelling in mild and slightly acidic mediums, respectively. In vivo performance was evaluated in the treatment of endoparasites in Corydoras fish. Systematically with a daily base oral administration, particles significantly reduced the infections over 15 days of treatment. The experiments provide evidence that utilizing particles granted and boosted the action of the antiparasitic drugs, leading to substantial reduction or elimination of infection. Hence, the pH-responsive particles represent a biomaterial with prominent characteristics that is promising for the development of targeted oral drug delivery.

A simple strategy for robust preparation and characterisation of hydrogels derived from chitosan and amino functional monomers for biomedical applications.

Molecular interactions of amino functional (AF) monomers with chitosan (CS) lead to the formation of external stimuli responsive hydrogels (HGs). These have the potential to produce biomaterials with novel properties by a simple blending approach. Six independent AF monomers such as diethylenetriamine (DETA), bis(3-aminopropyl)amine (BAPA), 3,3'-diamino-N-methyldipropyleamine (DAMPA), hexamethylenediamine (HMDA), N,N-dimethylethylamine (DMEA) and diethylamine (DEA) with distinct functional groups and chain lengths were designed to form stable HGs at physiological pH. Such AF monomers are able to form HGs within a short time (in the range from 10 to 19 seconds) by physically interacting with CS. This is an alternative to the covalently crosslinking reaction process, providing cost effective HG biomaterials. HG complexes were characterized by rheometry, differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. The interaction between AF monomers and the CS polymer has been discussed and the results have been confirmed by FTIR analysis. The storage modulus (G'), loss modulus (G'') and complex viscosity (η*) were evaluated for all HGs using a rheometer, and the ratios of CS and the particular AF monomer were optimized for stable HG formation. The swelling ratio was evaluated using a simple method and was found to be directly related to the structure of the AF monomer, pH and temperature. These HGs were utilised for encapsulation, and the release of active molecules (e.g., reactive red 120 (RR120) as a model compound) was measured at low pH 5.5, physiological pH 7.4 and high pH 9.5. The cell viability and cellular compatibility of the HGs were evaluated in vitro cell culture, demonstrating that all the five different types of HGs support cellular compatibility, attachment and growth. The physical mixing of AF monomers with CS is expedited for the development of new bespoke economically viable biomaterials.

A DFT based analysis of adsorption of Hg2+ ion on chitosan monomer and its citralidene and salicylidene derivatives: Prior to the removal of Hg toxicity

A Density functional theory based study of adsorption of the toxic metal Hg (II) ion by chitosan monomer and two of its derivatives; citralidene and salicylidene chitosan, has been performed. The effect of structural features on the stability of studied complexes has been analyzed by using Gaussian03 software package. All the possible conformations of these adsorbents were studied using the global minimum geometries. All the adsorbing sites were studied by placing the metal ion on the centroid of the atoms and the stable conformer of the adsorbent-metal ion complex was identified. Interaction between Hg (II) and the adsorbents is found to be electrostatic. Metal ion binding with nitrogen atom is stronger than that with oxygen atoms in all the cases as the charge density of nitrogen is enhanced on Schiff base formation. The advantage of derivatives over chitosan monomer is their stability in acidic media. ΔE value of the complexes are in the order SC–Hg (II)>chitosan–Hg (II)>CC–Hg (II) which indicates that the stability of complexes increases with increase in energy gap. The study reveals that aromatic Schiff base derivatives of chitosan is better for Hg(II) intake than aliphatic derivatives.

Nanoparticle-induced assembly of hydrophobically modified chitosan

Hydrophobically modified chitosan (HMC) self-assembles in solution to form gels, making it suitable for applications in oil dispersion, hydrogel design and wound dressing. The self-assembly of HMC is driven by the association of hydrophobic moieties that are attached to chitosan monomers along the polymer chain. We present the results of discontinuous molecular dynamics simulations aimed at understanding how the length and density of the hydrophobic modification chains attached to HMC affect self-assembly and the structure of the resulting network. Long modification chains are required to promote the formation of a stable network in solution at a modification density of 5%; the networks form more readily at a modification density of 10%. The pore size distribution of the resulting HMC network is relatively independent of the modification chain length and density. Insertion of different sized hydrophobic nanoparticles into HMC has a significant impact on network formation, with the particles acting as junction points that promote the association of several HMC chains. The networks form faster in the presence of many small nanoparticles than in the presence of few large nanoparticles. We conclude that HMC could be a viable candidate to form hydrogels in solution.

New insights into the nature of the Cibacron brilliant red 3B-A – Chitosan interaction

Abstract Cibacron brilliant red 3B-A (CBR) has been introduced to determine chitosan (CS) concentrations in solution, and several studies applied it to measure chitosan content in pharmaceutical formulations. So far, studies have relied on the absorbance band shift to 570 nm to determine the extent of the CBR – CS interaction. In this study, we show that CBR forms micro- to nanometer sized aggregates with CS, depending on their charge ratio and that other photophysical changes in CBR are induced by this interaction. We found that, besides the bathochromic band shift, aggregation induces emission at 600 nm and emission quenching at 360 nm. We compared changes CS induced in absorbance and fluorescence emission of CBR with the CS monomer glucosamine and poly(allylamine) hydrochloride, which both contain amino groups, and found that similar but less intense photophysical changes also occur. Furthermore, CS-induced circular dichroism in CBR suggests a twisted, chiral structure of these aggregates that should match with the previously published in silico simulations of the structure of CS in solution. The low linear charge density of CS and its chiral conformation are considered responsible for the enhanced photophysical response of CBR interacting with the polycation.

Estimating the energy of intramolecular hydrogen bonds in chitosan oligomers

The effect the number of chitosan monomer units CTSn (n = 1–5), the protonation of chitosan dimers, and the interaction between CTSn (n = 1–3) and acetate ions have on the energy of intramolecular hydrogen bonds is investigated by means of QTAIM analysis and solving the vibrational problem within the cluster-continuum model. It is established that the number of H-bonds in CTSn is 2n − 1 and the total energy of H-bonds grows by ~20 kJ/mol. It is concluded that the hydrogen bonds between CTS and acetate ions play a major role in the stabilization of polyelectrolyte complexes in dilute acetic acid solutions of CTS.

Theoretical study of the reaction of chitosan monomer with 2,3-epoxypropyl-trimethyl quaternary ammonium chloride catalyzed by an imidazolium-based ionic liquid

The molecular mechanism of the graft reaction of 2,3-epoxypropyl-trimethyl quaternary ammonium chloride with chitosan monomer was investigated by performing density functional theory (DFT) calculations. The calculated results show that the −NH2 group of chitosan monomer is more reactive than its −OH and −CH2OH groups, and the graft reaction on the −NH2 group is calculated to be exothermic by 20.5kcal/mol with a free energy barrier of 42.6kcal/mol. The reaction cannot benefit from the presence of the intruded water molecule, but can be considerably assisted by 1-allyl-3-methylimidazolium chloride ([Amim]Cl) ionic liquid. The reaction catalyzed by the ion-pair is calculated to be exothermic by 36.5kcal/mol and the barrier is reduced to 29.3kcal/mol, which are further corrected to 28.0 and 29.1kcal/mol by considering the solvent effect of [Amim]Cl ionic liquid. Calculated results verified the experimental finding that imidazolium-based ionic liquids can promote the reaction of chitosan with epoxy compounds.

Towards a selective adsorbent for arsenate and selenite in the presence of phosphate: Assessment of adsorption efficiency, mechanism, and binary separation factors of the chitosan-copper complex

The potential for a chitosan-copper polymer complex to select for the target contaminants in the presence of their respective competitive ions was evaluated by synthesizing chitosan-copper beads (CCB) for the treatment of (arsenate:phosphate), (selenite:phosphate), and (selenate:sulfate). Based on work by Rhazi et al., copper (II) binds to the amine moiety on the chitosan backbone as a monodentate complex (Type I) and as a bidentate complex crosslinking two polymer chains (Type II), depending on pH and copper loading. In general, the Type I complex exists alone; however, beyond threshold conditions of pH 5.5 during synthesis and a copper loading of 0.25 mol Cu(II)/mol chitosan monomer, the Type I and Type II complexes coexist. Subsequent chelation of this chitosan-copper ligand to oxyanions results in enhanced and selective adsorption of the target contaminants in complex matrices with high background ion concentrations. With differing affinities for arsenate, selenite, and phosphate, the Type I complex favors phosphate chelation while the Type II complex favors arsenate chelation due to electrostatic considerations and selenite chelation due to steric effects. No trend was exhibited for the selenate:sulfate system possibly due to the high Ksp of the corresponding copper salts. Binary separation factors, α12, were calculated for the arsenate-phosphate and selenite-phosphate systems, supporting the mechanistic hypothesis. While, further research is needed to develop a synthesis method for the independent formation of the Type II complexes to select for target contaminants in complex matrices, this work can provide initial steps in the development of a selective adsorbent.

Virtual screening of molecular properties of chitosan and derivatives in search for druggable molecules

Druggability of chitosan monomer and Schiff bases as well as reduced Schiff base derivatives of chitosan were examined. Oral bioavailability and bioactivity of all these molecules against selected drug targets as well as ADME/Tox studies were conducted. All the molecules satisfied Lipinski's rule of five confirming their oral bioavailability. They also show good bioactivity score for protease and enzyme inhibition. ADME/Tox studies conducted shows that almost all the derivatives are free from toxicity risks. It is observed that these molecules exhibit fairly good drug score and are orally viable molecules. Chelation of chitosan and its derivatives with essential metal ions might be the mechanism driving their bioactivity. Thus chitosan monomer and the derivatives studied, can serve as good lead molecules for further research.

Chitosan-glutaraldehyde copolymers and their sorption properties

This study reports the preparation of chitosan-glutaraldehyde (Chi-Glu) copolymers at modified reaction conditions such as the temperature prior to gelation, pH, and reagent ratios. The chitosan copolymers were characterized using infrared spectroscopy (FT-IR), CHN elemental analysis, and thermal gravimetric analysis (TGA). Evidence of self-polymerized glutaraldehyde was supported by CHN and TGA results. The sorption properties of Chi-Glu copolymers were evaluated in aqueous solutions containing p-nitrophenol at variable pH (4.6, 6.6, and 9.0). The sorption properties of the copolymers correlated with the level of the accessibility of the sorption sites in accordance with the relative cross-linker content. The relative sorption capacity of the Chi-Glu copolymers increases as the level of cross-linking increases. Chitosan displays the lowest sorptive uptake while an optimal sorption capacity was concluded at the 4:1 glutaraldehyde:chitosan monomer mole ratio, in close agreement with the three reactive sites (i.e. OH/NH) per glucosamine monomer. The PNP dye probe was determined to bind to chitosan through an electrostatic interaction due to the increased sorption capacity of the phenolate anion, as evidenced by the change in pH from 4.6 to 9.0.

Differential interactions and structural stability of chitosan oligomers with human serum albumin and α-1-glycoprotein

Chitosan is a naturally occurring deacetylated derivative of chitin with versatile biological activities. Here, we studied the interaction of chitosan oligomers with low degree of polymerization such as chitosan monomer (CM), chitosan dimer (CD), and chitosan trimer (CT) with human serum albumin (HSA) a major blood carrier protein and α-1-glycoprotein (AGP). Since, HSA and AGP are the two important plasma proteins that determine the drug disposition and affect the fate of distribution of drugs. Fluorescence emission spectra indicated that CM, CD, and CT had binding constants of KCM = 6.2 ± .01 × 105 M−1, KCD = 5.0 ± .01 × 104 M−1, and KCT = 1.6 ± .01 × 106 M−1, respectively, suggesting strong binding with HSA. However, binding of chitooligomers with AGP was insignificant. Thermodynamic and molecular docking analysis indicated that hydrogen bonds and also hydrophobic interaction played an important role in stabilizing the HSA-chitooligomer complexes with free energies of −7.87, −6.35, and −8.4 Kcal/mol for CM, CD, and CT, respectively. Further, circular dichroism studies indicated a minor unfolding of HSA secondary structure, upon interaction with chitooligomers, which are supported with fluctuations of root mean square deviation (RMSD) and radius of gyration (Rg) of HSA. Docking analysis revealed that all three chitooligomers were bound to HSA within subdomain IIA (Site I). In addition, RMSD and Rg analysis depicted that HSA-chitooligomer complexes stabilized at around 4.5 ns. These results suggest that HSA might serve as a carrier in delivering chitooligomers to target tissues than AGP which has pharmacological importance.

Synthesis of LiFePO<sub>4</sub>/C Cathode by Sol-gel and Calcining Method with Chitosan Monomer

Synthesis of LiFePO<sub>4</sub>/C Cathode by Sol-gel and Calcining Method with Chitosan Monomer