Factors responsible for the aggregation behavior of hydrophobic polyelectrolyte PEA in aqueous solution studied by molecular dynamics simulations

Sappidi, Praveenkumar; Natarajan, Upendra

doi:10.1016/j.jmgm.2017.04.007

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…Such an approach has been widely used in the past to provide accurate results for polymers of short chain lengths in aqueous solution. Simulations were run for 90 ns and up to 200 ns; such long MD trajectory times are not unusual or unprecedented but are much more than those typically used (50–60 ns) in the recent literature, ,,, obtaining correct sampling of flexible water-soluble synthetic homopolymer atomistic simulations in explicit water. Although those earlier studies were carried out only at a fixed temperature, the present study looks at temperature and concentration effects.…”

Section: System Setup Parameters and Simulation Methodologymentioning

confidence: 99%

“…The GROMOS set of force fields are suitable for the simulations of water-soluble polymers in aqueous solution. − The SPC water model, which is a well-known and a widely used simple model, was used for the description of water molecules as this water model is easy and fast to implement and gives acceptable results for the structure of liquid water at ambient temperatures. The SPC water model along with this force field has been used for the simulation of aqueous solutions of PVA and other synthetic polymers. − , The partial charges for atoms in the PVA repeating units, given in Table S1 in the Supporting Information, were taken from an earlier simulation study on PVA in aqueous solution available in the literature . Energy minimization, equilibration, and production runs in NPT ensemble were carried out using the GROMACS 2016 simulation program .…”

Section: System Setup Parameters and Simulation Methodologymentioning

confidence: 99%

“…The SPC water model along with this force field has been used for the simulation of aqueous solutions of PVA 9 and other synthetic poly- mers. [21][22][23]26 The partial charges for atoms in the PVA repeating units, given in Table S1 in the Supporting Information, were taken from an earlier simulation study on PVA in aqueous solution available in the literature. 9 Energy minimization, equilibration, and production runs in NPT ensemble were carried out using the GROMACS 2016 simulation program.…”

Section: System Setup Parameters and Simulationmentioning

confidence: 99%

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Factors Responsible for the Aggregation of Poly(vinyl alcohol) in Aqueous Solution as Revealed by Molecular Dynamics Simulations

Kurapati

Natarajan

2020

Ind. Eng. Chem. Res.

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Molecular dynamics simulations are used to study the structure and dynamics of poly(vinyl alcohol) and water in aqueous solution as a function of concentration at different temperatures in the range of 278–338 K. Simulations were performed using multiple oligomeric chains for facilitating interchain interactions as well as a direct comparison with experimental data. PVA chains fold and bundle up to form an aggregate in solution. The intermolecular spatial distributions show the structure of aggregate to be ordered. PVA chains show a high tendency to form intrachain hydrogen bonds between adjacent repeating units, instead of interchain H-bonds, indicating hydrophobic effect as the major driving force for aggregate formation. At all temperatures, the conformations of a single PVA chain by itself in solution are unstable, going back and forth between extended and folded states. However, interchain interactions among PVA chains in the aggregate stabilize the folded conformation. An increase in temperature results in faster motions and an increase in concentration results in slower dynamics. At higher concentration, the chains adopt a single folded state independent of temperature so that there is an insignificant effect on R g. The competition between the formation of various hydrogen bonds such as intrachain, interchain, and PVA–water is the key to understand the solvation behavior of PVA. The activation energy for the conformational transition between the trans and gauche states of backbone dihedrals obtained from the simulations is 15.73 kJ/mol, which is close to the value of 13.4 kJ/mol obtained from experiments for 15 wt % PVA solution. The hydrophobic effect rather than interchain PVA hydrogen bonding is the major driving force for the aggregation of PVA in water.

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Section: System Setup Parameters and Simulation Methodologymentioning

confidence: 99%

Section: System Setup Parameters and Simulation Methodologymentioning

confidence: 99%

Section: System Setup Parameters and Simulationmentioning

confidence: 99%

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Factors Responsible for the Aggregation of Poly(vinyl alcohol) in Aqueous Solution as Revealed by Molecular Dynamics Simulations

Kurapati

Natarajan

2020

Ind. Eng. Chem. Res.

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“…Some polymer pharmaceutical additives are reported to interact electrostatically with other compounds. [17][18][19][20][21][22] Salamanca et al reported that ampicillin trihydrate, a zwitterionic ingredient, formed a complex with amino-alkyl methacrylate, another polymer pharmaceutical additive, via electrostatic interaction. 23) Since levofloxacin has two pKs (pK a1 6.11 and pK a2 8.18), it would form a zwitterion under neutral conditions, 24) so we considered that levofloxacin and methacrylic acid copolymer LD might aggregate via electrostatic interaction.…”

Section: Discussionmentioning

confidence: 99%

Examination of Aggregate Formation upon Simultaneous Dissolution of Methacrylic Acid Copolymer LD Enteric Coating Agent, Pharmaceutical Additives, and Zwitterionic Ingredients

Nakagawa

Suzuki

Suga

et al. 2020

Biological & Pharmaceutical Bulletin

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We previously showed that adhesive aggregates were formed when levofloxacin hydrate tablets and lansoprazole orally disintegrating (OD) tablets were suspended in water in the clinical context. In this study, we have clarified the factors causing aggregate formation, focusing on the role of pharmaceutical additives and electrostatic interaction. Co-suspension of enteric-coated proton pump inhibitor (PPI) esomeprazole magnesium hydrate with levofloxacin resulted in aggregate formation, whereas the non-enteric-coated PPI vonoprazan fumarate did not. A comparison of pharmaceutical additive in the two PPIs highlighted polysorbate 80 and methacrylic acid copolymer LD as candidates causing aggregation. When these pharmaceutical additives were added to levofloxacin, only methacrylic acid copolymer LD induced aggregate formation. Since levofloxacin is zwitterionic, we examined another zwitterionic ingredient, ampicillin sodium, and found that it also formed aggregates with methacrylic acid copolymer LD, while benzylpenicillin sodium, which is not zwitterionic, did not form aggregates. When we next examined a series of zwitterionic quinolone antimicrobial drugs, we found that ofloxacin, which is highly soluble, formed aggregates with lansoprazole OD tablets, whereas poorly soluble quinolone antimicrobial drugs did not form aggregates. Further, although cefepime hydrochloride and cephalexin did not form aggregates with methacrylic acid copolymer LD in tap water, aggregates were formed when a suspension of cefepime hydrochloride or cephalexin with methacrylic acid copolymer LD was adjusted to pH 7.0. Our results indicate that electrostatic interaction between zwitterionic ingredients and methacrylic acid copolymer LD can result in aggregate formation under conditions where the drug and methacrylic acid copolymer LD are both sufficiently soluble.

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“…A role of pH and ionic strength in polymer conformation of PAA n with large molecular weight (M w and n reached up to 50 kDa and 700 units, respectively) has been studied by using the fluorescence correlation spectroscopy and Monte Carlo simulations [23]. Finally, self-association behavior of oligomers of PAA has also been modeled [27,28]. Recently, Sulatha and Natarajan [29] have adopted the GROMOS G53a6 united atom FFs suitable for MD simulations of a single chain PAA oligomer in water.…”

Section: Poly(acrylic Acid) Force Fieldmentioning

confidence: 99%

Structure and Dynamics of Pyrene-Labeled Poly(acrylic acid): Molecular Dynamics Simulation Study

Slavgorodska¹,

Kyrychenko²

2020

ChChT

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1 An atomistic model for molecular dynamics (MD) simulations of the single chain poly(acrylic acid) (PAA), terminally substituted with two pyrene moieties, was developed. MD simulations of the structure and conformational dynamics of pyrene-labeled PAA for a varying dissociation degree ( α ) of the COOH group revealed that the attachment of pyrene dyes to PAA alters significantly its conformational behavior. At acidic pH (α = 0), the PAA chain collapsed into the random coil conformation, so that the two pyrene moieties formed the stable π-π stacking structure. However, at basic pH (α = 1), the PAA chain was expanded and stretched facing the pyrene dyes apart into aqueous solution.

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Factors responsible for the aggregation behavior of hydrophobic polyelectrolyte PEA in aqueous solution studied by molecular dynamics simulations

Cited by 10 publications

References 40 publications

Factors Responsible for the Aggregation of Poly(vinyl alcohol) in Aqueous Solution as Revealed by Molecular Dynamics Simulations

Factors Responsible for the Aggregation of Poly(vinyl alcohol) in Aqueous Solution as Revealed by Molecular Dynamics Simulations

Examination of Aggregate Formation upon Simultaneous Dissolution of Methacrylic Acid Copolymer LD Enteric Coating Agent, Pharmaceutical Additives, and Zwitterionic Ingredients

Structure and Dynamics of Pyrene-Labeled Poly(acrylic acid): Molecular Dynamics Simulation Study

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