Enzymatic synthesis of polyesters

The use of enzymes as catalysts is gaining widespread use due to the need to move into green chemistry approaches. This has been fostered also by the discovery that enzymes can function in novel environments such as environmental extremes and organic solvents. In this work, soybean oil was used as the raw material to synthesize a dicarboxylic acid, which was then polymerized to get polyester. A commercially available lipoxygenase was used to form a conjugated hydroperoxide at carbon thirteen from the free fatty acids obtained from soybean oil hydrolysis. This reaction was followed by a reaction with hydroperoxide lyase derived from tomato leaves, thereby forming the 12-oxo-dodeceneoic acid and a 6-carbon aldehyde. Traumatic acid, a 12 carbon dicarboxylic acid, was formed by oxidation of 12-oxo-dodeceneoic acid. The traumatic acid thus formed was enzymatically polymerized using Novozym 435-Lipase CA to obtain the polyester. The products of each reaction were analyzed by Gas Chromatography/ Liquid Chromatography combined with Mass Spectroscopy. Gel Permeation Chromatography was used to confirm the molecular weight of the polyester --Abstract, page iii

Molecular studies of peptides at solid-liquid interfaces

Monte Carlo simulation runs were performed on a negatively charged model peptide (consisting of diblock units of aspartic acid and isoleucine residues) adsorbed at a charged model surface (consisting of CH₂ atoms) in vacuum, and in presence of various solvent compositions (by addition of cosolvents) to study the conformational and orientational aspects of peptides at solid surfaces:--Abstract, page iv

Conformational Changes of Peptides at Solid/Liquid Interfaces: A Monte Carlo Study

Monte Carlo simulations were performed to study the conformational changes of negatively charged model peptides dissolved in water adsorbed onto charged surfaces. 8-, 16-, and 20-residues peptides were used, each of them consisted of repeating diblock units of aspartic acid (ASP, polar amino acid) and isoleucine (ILE, nonpolar amino acid) residues. We found that a water patch was retained at the charged surface, separating the peptide from it. We believed that these water molecules were primarily responsible for giving a particular orientation to the peptide at the surface. Water did play a role to some extent in the structural stability of the 8-residues peptide. However, for higher chain lengths (16-residues and 20-residues), the intrinsic hydrogen-bonding network (or intrinsic structural stability) showed a predominant effect over hydrophobic dehydration for the stability of the peptide at the surface

Effect of Co-Solvents on the Adsorption of Peptides at the Solid-Liquid Interface

The adsorption of a peptide at solid surfaces is the result of a complex interplay of interactions between the peptide, solvent, and surface. In this work, Monte Carlo simulations were performed to evaluate the effect of the solvent hydrogen bonding ability on the adsorption of the peptide ASP1-ASP2-ILE3-ILE4-ASP5-ASP6-ILE7-ILE8 at a charged surface consisting of CH2 atoms with a fixed lattice arrangement. Various water-alcohol mixtures were used as solvent because alcohols are known to alter the dielectric constant, hydrophobicity, and hydrogen bonding capacity of water. Solvent-solvent, solvent-surface, solvent-peptide, and peptide-surface interactions were studied independently and correlated with the observed peptide behavior at the solvent-surface interface. We concluded that the behavior (and orientation) of the peptide at the surface is directly related to changes in water-water hydrogen bonding properties in water-alcohol mixtures. In the presence of increasing concentrations of methanol, the strength of solvent-peptide and solvent-surface interactions was reduced, and as a result, a stronger interaction between the peptide and the surface was observed. Stronger solvent-peptide and solvent-surface interactions were responsible for a weaker interaction of the peptide with the surface in the presence of increasing concentrations of glycerol. These results suggest that by changing solvent conditions it is possible to finely tune the orientation of a macromolecule at solid/liquid interfaces

Unrecognized clozapine-related constipation leading to fatal intra-abdominal sepsis – a case report

Vikram Oke, Frances Schmidt, Bikash Bhattarai, Md Basunia, Chidozie Agu, Amrit Kaur, Danilo Enriquez, Joseph Quist, Divya Salhan, Vijay Gayam, Prajakta Mungikar Department of Pulmonary Medicine, Interfaith Medical Center, NY, USA Abstract: Clozapine is the preferred antipsychotic used for the treatment of resistant schizophrenia with suicidal ideation. The drug is started at a low dose and gradually increased to a target dose of 300–450 mg/day. It is well known to cause agranulocytosis and neutropenia. Several cases of fatal sepsis have been reported in neutropenic patients and emphasis is placed on monitoring for agranulocytosis; however, clozapine also causes intestinal hypomotility and constipation, which if unrecognized can lead to intestinal obstruction, bowel necrosis, and intra-abdominal sepsis. Reduced behavioral pain reactivity in schizophrenics may alter the ability to express pain, potentially leading to a delay in the presentation for medical attention. We report a case of fatal intra-abdominal sepsis secondary to an unrecognized case of clozapine-related constipation. Keywords: antipsychotics, clozapine, schizophrenia, syncope, constipation, sepsi

Quality by design: Scale-up of freeze-drying cycles in pharmaceutical industry

This paper shows the application of mathematical modeling to scale-up a cycle developed with lab-scale equipment on two different production units. The above method is based on a simplified model of the process parameterized with experimentally determined heat and mass transfer coefficients. In this study, the overall heat transfer coefficient between product and shelf was determined by using the gravimetric procedure, while the dried product resistance to vapor flow was determined through the pressure rise test technique. Once model parameters were determined, the freeze-drying cycle of a parenteral product was developed via dynamic design space for a lab-scale unit. Then, mathematical modeling was used to scale-up the above cycle in the production equipment. In this way, appropriate values were determined for processing conditions, which allow the replication, in the industrial unit, of the product dynamics observed in the small scale freeze-dryer. This study also showed how inter-vial variability, as well as model parameter uncertainty, can be taken into account during scale-up calculations