Short range order of CCl4: RMC and MD methods

The main objective of this paper is to present a method to fully determine the six degrees of freedom regarding position and orientation of a neighboring molecule around a central one, i.e. the g(rCM,¿) distribution function. This is accomplished by completely determining the short range structure of liquid carbon tetrachloride, while employing results from two different methods, Molecular Dynamics (MD) [1] and Reverse Monte Carlo (RMC) [2]. Exclusively, the structural ordering of the first four molecules will be detailed.Postprint (published version

On the structure of prilocaine in aqueous and amphiphilic solutions

The solvation of prilocaine has been investigated in pure water and in an amphiphilic methanol/water solution using a combination of neutron diffraction with isotopic substitution augmented by Empirical Potential Structure Refinement (EPSR) simulations. This combination of techniques allows for details of the solvation structure on the atomic scale to be unravelled. The hydration of prilocaine is significantly altered relative to when this molecule is in pure water (as a hydrochloride salt) or in an amphiphilic environment (as a freebase compound). Interestingly, there is not a significant change in hydration around the amine group on prilocaine hydrochloride compared with prilocaine as a freebase. Despite this group being an ammonium group in water and an amine group in methanol/water solutions, the hydration of this motif remains largely intact. The changes in hydration between prilocaine as a free base and prilocaine·HCl instead appears to arise from a change in hydration around the aromatic ring and the amide group in the prilocaine molecule.Peer ReviewedPostprint (published version

L'estructura atomica de la prilocaina en solucio

The project is aimed to unravel the physic mechanisms behind the enhancement of drug stability by addition of water. The project will deal with prilocaine, an anesthetic mainly used in dentistry.Prilocaine is an aminoamide local anesthetic (LA). LAs are known to act on functional proteins as well as mediating membrane structure in order to induce anesthetic action, however there is no consensus as to which molecular mechanisms exert these effects. As such, this project aims to understand the structure of prilocaine in physiologically relevant environments, by means of two techniques: neutron diffraction with isotopic substitution (NDIS) and computational modelling with Empirical Potential Structure Refinement (EPSR). EPSR is a reverse Monte Carlo technique used to model liquids, which is constrained by diffraction data obtained by NDIS. Two distinct solutions have been investigated: prilocaine hydrochloride in water (1:150 molar ratio) and prilocaine freebase in methanol and water (1:75:75). The former system provides insight as to how prilocaine is hydrated. This occurs by water coordinating around its -C=O carbonyl oxygen, amide and amine nitrogens, as well as through relatively highly localized, but non-oriented, water molecules around the benzene ring. The latter system has shed light on amphiphilic interactions in- volving prilocaine, as methanol molecules are also amphiphilic; they possess a hydrophilic hydroxyl -OH group and a hydrophobic methyl -CH 3 group. Prilocaine in an amphiphilic environment is slightly dehydrated overall, as compared to a purely aqueous environment; this is especially interesting in the amide group, where hydration shifts from the nitrogen to the carbonyl oxygen. In addition, methanol, but not water, seems to bind to the ben- zene ring, which could have implications as to how the benzene ring could confer solubility in a hydrophobic milieu, as well as to how prilocaine could alter the structure of the hydrocarbon interior of membranes. These two systems have also been exploited to observe differences in the charged and uncharged form of prilocaine, as uncharged prilocaine is not soluble in water. Uncharged prilo- caine appears to coordinate water more weakly, but presents a single highly localized water molecule binding to both amide oxygen and amine nitrogen, which could shield these hydrophilic groups in penetrating the hydrophobic region of cell membranes.Prilocaine is an aminoamide local anesthetic (LA). LAs are known to act on functional proteins as well as mediating membrane structure in order to induce anesthetic action, however there is no consensus as to which molecular mechanisms exert these effects. As such, this project aims to understand the structure of prilocaine in physiologically relevant environments, by means of two techniques: neutron diffraction with isotopic substitution (NDIS) and computational modelling with Empirical Potential Structure Refinement (EPSR). EPSR is a reverse Monte Carlo technique used to model liquids, which is constrained by diffraction data obtained by NDIS. Two distinct solutions have been investigated: prilocaine hydrochloride in water (1:150 molar ratio) and prilocaine freebase in methanol and water (1:75:75). The former system provides insight as to how prilocaine is hydrated. This occurs by water coordinating around its -C=O carbonyl oxygen, amide and amine nitrogens, as well as through relatively highly localized, but non-oriented, water molecules around the benzene ring. The latter system has shed light on amphiphilic interactions in- volving prilocaine, as methanol molecules are also amphiphilic; they possess a hydrophilic hydroxyl -OH group and a hydrophobic methyl -CH 3 group. Prilocaine in an amphiphilic environment is slightly dehydrated overall, as compared to a purely aqueous environment; this is especially interesting in the amide group, where hydration shifts from the nitrogen to the carbonyl oxygen. In addition, methanol, but not water, seems to bind to the ben- zene ring, which could have implications as to how the benzene ring could confer solubility in a hydrophobic milieu, as well as to how prilocaine could alter the structure of the hydrocarbon interior of membranes. These two systems have also been exploited to observe differences in the charged and uncharged form of prilocaine, as uncharged prilocaine is not soluble in water. Uncharged prilo- caine appears to coordinate water more weakly, but presents a single highly localized water molecule binding to both amide oxygen and amine nitrogen, which could shield these hydrophilic groups in penetrating the hydrophobic region of cell membranes.Prilocaine is an aminoamide local anesthetic (LA). LAs are known to act on functional proteins as well as mediating membrane structure in order to induce anesthetic action, however there is no consensus as to which molecular mechanisms exert these effects. As such, this project aims to understand the structure of prilocaine in physiologically relevant environments, by means of two techniques: neutron diffraction with isotopic substitution (NDIS) and computational modelling with Empirical Potential Structure Refinement (EPSR). EPSR is a reverse Monte Carlo technique used to model liquids, which is constrained by diffraction data obtained by NDIS. Two distinct solutions have been investigated: prilocaine hydrochloride in water (1:150 molar ratio) and prilocaine freebase in methanol and water (1:75:75). The former system provides insight as to how prilocaine is hydrated. This occurs by water coordinating around its -C=O carbonyl oxygen, amide and amine nitrogens, as well as through relatively highly localized, but non-oriented, water molecules around the benzene ring. The latter system has shed light on amphiphilic interactions in- volving prilocaine, as methanol molecules are also amphiphilic; they possess a hydrophilic hydroxyl -OH group and a hydrophobic methyl -CH 3 group. Prilocaine in an amphiphilic environment is slightly dehydrated overall, as compared to a purely aqueous environment; this is especially interesting in the amide group, where hydration shifts from the nitrogen to the carbonyl oxygen. In addition, methanol, but not water, seems to bind to the ben- zene ring, which could have implications as to how the benzene ring could confer solubility in a hydrophobic milieu, as well as to how prilocaine could alter the structure of the hydrocarbon interior of membranes. These two systems have also been exploited to observe differences in the charged and uncharged form of prilocaine, as uncharged prilocaine is not soluble in water. Uncharged prilo- caine appears to coordinate water more weakly, but presents a single highly localized water molecule binding to both amide oxygen and amine nitrogen, which could shield these hydrophilic groups in penetrating the hydrophobic region of cell membranes

L'estructura atomica de la prilocaina en solucio

The project is aimed to unravel the physic mechanisms behind the enhancement of drug stability by addition of water. The project will deal with prilocaine, an anesthetic mainly used in dentistry.Prilocaine is an aminoamide local anesthetic (LA). LAs are known to act on functional proteins as well as mediating membrane structure in order to induce anesthetic action, however there is no consensus as to which molecular mechanisms exert these effects. As such, this project aims to understand the structure of prilocaine in physiologically relevant environments, by means of two techniques: neutron diffraction with isotopic substitution (NDIS) and computational modelling with Empirical Potential Structure Refinement (EPSR). EPSR is a reverse Monte Carlo technique used to model liquids, which is constrained by diffraction data obtained by NDIS. Two distinct solutions have been investigated: prilocaine hydrochloride in water (1:150 molar ratio) and prilocaine freebase in methanol and water (1:75:75). The former system provides insight as to how prilocaine is hydrated. This occurs by water coordinating around its -C=O carbonyl oxygen, amide and amine nitrogens, as well as through relatively highly localized, but non-oriented, water molecules around the benzene ring. The latter system has shed light on amphiphilic interactions in- volving prilocaine, as methanol molecules are also amphiphilic; they possess a hydrophilic hydroxyl -OH group and a hydrophobic methyl -CH 3 group. Prilocaine in an amphiphilic environment is slightly dehydrated overall, as compared to a purely aqueous environment; this is especially interesting in the amide group, where hydration shifts from the nitrogen to the carbonyl oxygen. In addition, methanol, but not water, seems to bind to the ben- zene ring, which could have implications as to how the benzene ring could confer solubility in a hydrophobic milieu, as well as to how prilocaine could alter the structure of the hydrocarbon interior of membranes. These two systems have also been exploited to observe differences in the charged and uncharged form of prilocaine, as uncharged prilocaine is not soluble in water. Uncharged prilo- caine appears to coordinate water more weakly, but presents a single highly localized water molecule binding to both amide oxygen and amine nitrogen, which could shield these hydrophilic groups in penetrating the hydrophobic region of cell membranes.Prilocaine is an aminoamide local anesthetic (LA). LAs are known to act on functional proteins as well as mediating membrane structure in order to induce anesthetic action, however there is no consensus as to which molecular mechanisms exert these effects. As such, this project aims to understand the structure of prilocaine in physiologically relevant environments, by means of two techniques: neutron diffraction with isotopic substitution (NDIS) and computational modelling with Empirical Potential Structure Refinement (EPSR). EPSR is a reverse Monte Carlo technique used to model liquids, which is constrained by diffraction data obtained by NDIS. Two distinct solutions have been investigated: prilocaine hydrochloride in water (1:150 molar ratio) and prilocaine freebase in methanol and water (1:75:75). The former system provides insight as to how prilocaine is hydrated. This occurs by water coordinating around its -C=O carbonyl oxygen, amide and amine nitrogens, as well as through relatively highly localized, but non-oriented, water molecules around the benzene ring. The latter system has shed light on amphiphilic interactions in- volving prilocaine, as methanol molecules are also amphiphilic; they possess a hydrophilic hydroxyl -OH group and a hydrophobic methyl -CH 3 group. Prilocaine in an amphiphilic environment is slightly dehydrated overall, as compared to a purely aqueous environment; this is especially interesting in the amide group, where hydration shifts from the nitrogen to the carbonyl oxygen. In addition, methanol, but not water, seems to bind to the ben- zene ring, which could have implications as to how the benzene ring could confer solubility in a hydrophobic milieu, as well as to how prilocaine could alter the structure of the hydrocarbon interior of membranes. These two systems have also been exploited to observe differences in the charged and uncharged form of prilocaine, as uncharged prilocaine is not soluble in water. Uncharged prilo- caine appears to coordinate water more weakly, but presents a single highly localized water molecule binding to both amide oxygen and amine nitrogen, which could shield these hydrophilic groups in penetrating the hydrophobic region of cell membranes.Prilocaine is an aminoamide local anesthetic (LA). LAs are known to act on functional proteins as well as mediating membrane structure in order to induce anesthetic action, however there is no consensus as to which molecular mechanisms exert these effects. As such, this project aims to understand the structure of prilocaine in physiologically relevant environments, by means of two techniques: neutron diffraction with isotopic substitution (NDIS) and computational modelling with Empirical Potential Structure Refinement (EPSR). EPSR is a reverse Monte Carlo technique used to model liquids, which is constrained by diffraction data obtained by NDIS. Two distinct solutions have been investigated: prilocaine hydrochloride in water (1:150 molar ratio) and prilocaine freebase in methanol and water (1:75:75). The former system provides insight as to how prilocaine is hydrated. This occurs by water coordinating around its -C=O carbonyl oxygen, amide and amine nitrogens, as well as through relatively highly localized, but non-oriented, water molecules around the benzene ring. The latter system has shed light on amphiphilic interactions in- volving prilocaine, as methanol molecules are also amphiphilic; they possess a hydrophilic hydroxyl -OH group and a hydrophobic methyl -CH 3 group. Prilocaine in an amphiphilic environment is slightly dehydrated overall, as compared to a purely aqueous environment; this is especially interesting in the amide group, where hydration shifts from the nitrogen to the carbonyl oxygen. In addition, methanol, but not water, seems to bind to the ben- zene ring, which could have implications as to how the benzene ring could confer solubility in a hydrophobic milieu, as well as to how prilocaine could alter the structure of the hydrocarbon interior of membranes. These two systems have also been exploited to observe differences in the charged and uncharged form of prilocaine, as uncharged prilocaine is not soluble in water. Uncharged prilo- caine appears to coordinate water more weakly, but presents a single highly localized water molecule binding to both amide oxygen and amine nitrogen, which could shield these hydrophilic groups in penetrating the hydrophobic region of cell membranes

On the structure of prilocaine in aqueous and amphiphilic solutions

The solvation of prilocaine has been investigated in pure water and in an amphiphilic methanol/water solution using a combination of neutron diffraction with isotopic substitution augmented by Empirical Potential Structure Refinement (EPSR) simulations. This combination of techniques allows for details of the solvation structure on the atomic scale to be unravelled. The hydration of prilocaine is significantly altered relative to when this molecule is in pure water (as a hydrochloride salt) or in an amphiphilic environment (as a freebase compound). Interestingly, there is not a significant change in hydration around the amine group on prilocaine hydrochloride compared with prilocaine as a freebase. Despite this group being an ammonium group in water and an amine group in methanol/water solutions, the hydration of this motif remains largely intact. The changes in hydration between prilocaine as a free base and prilocaine·HCl instead appears to arise from a change in hydration around the aromatic ring and the amide group in the prilocaine molecule.Peer Reviewe

Short range order of CCl4: RMC and MD methods

The main objective of this paper is to present a method to fully determine the six degrees of freedom regarding position and orientation of a neighboring molecule around a central one, i.e. the g(rCM,¿) distribution function. This is accomplished by completely determining the short range structure of liquid carbon tetrachloride, while employing results from two different methods, Molecular Dynamics (MD) [1] and Reverse Monte Carlo (RMC) [2]. Exclusively, the structural ordering of the first four molecules will be detailed