Surface area, volume and shape descriptors as a novel tool for polymer lead design and discovery

Christensen, Jonatan Riis; Meng-Lund, Helena; Grohganz, Holger; Poso, Antti; Laitinen, Tuomo; Korhonen, Ossi; Jørgensen, Lene; Pajander, Jari

doi:10.1016/j.ejps.2017.03.013

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…The results of this procedure are listed in row three of Table . The similarities between MVR (Figures S1 and S12) and PLS (Figure S13) are not very surprising given how these methods are likely capturing similar linear relationships between descriptors and productivity . The slightly better performance of the NN (Figure S14) may be due to its ability to capture nonlinear relationships.…”

Section: Resultsmentioning

confidence: 91%

DFT and QSAR Studies of Ethylene Polymerization by Zirconocene Catalysts

et al. 2019

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A computational study of olefin polymerization has been performed on 51 zirconocene catalysts. The catalysts can be categorized into three classes according to the ligand framework: class I, Cp2ZrCl2 (10 catalysts), class II, CpIndZrCl2 (38 catalysts), and class III, Ind2ZrCl2 (3 catalysts), Ind = η5-indenyl. Detailed reaction pathways, including chain propagation and chain termination steps, are modeled for ethylene polymerization using zirconocene catalysts. Optimized structures for reaction coordinates indicated the presence of α-agostic interactions in the transition states (TSs) for both the first and second ethylene insertions, as well as in the ethylene π-complex of the ZrnPr cation. However, β-agostic interactions predominate in the cationic n-propyl and n-pentyl intermediates. The calculated activation energy barrier energies show that the TS for the insertion of ethylene into the Zr–CH3 + bond is the highest point on the computed reaction coordinates. Quantitative structure–activity relationship studies were also performed for 38-mixed zirconocene dichlorides. This study, in concert with the previous work, suggests that the type of ring attached to Zr (Cp vs Ind) affects the reaction kinetics and thermodynamics less significantly than the type of substituents attached to the Cp and indenyl rings and that substituent effects are even greater than those arising from changing the metal (Zr vs Hf).

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Section: Resultsmentioning

confidence: 91%

DFT and QSAR Studies of Ethylene Polymerization by Zirconocene Catalysts

et al. 2019

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“…Recently there has been a growing interest in in-silico pharmaceutical excipients screening methods including bioavailability and solubility improvement agents such as soluble polymers, surfactants and nutraceutical cocrystals formers (Bergström et al, 2016;Christensen et al, 2017;Cysewski, 2017;Przybyłek et al, 2017). The major advantage of efficient theoretical approaches, important from the economic viewpoint, is reducing the time and reagents costs.…”

Section: Discussionmentioning

confidence: 99%

Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index

Cysewski

Przybyłek

2017

European Journal of Pharmaceutical Sciences

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New theoretical screening procedure was proposed for appropriate selection of potential cocrystal formers possessing the ability of enhancing dissolution rates of drugs. The procedure relies on the training set comprising 102 positive and 17 negative cases of cocrystals found in the literature. Despite the fact that the only available data were of qualitative character, performed statistical analysis using binary classification allowed to formulate quantitative criterions. Among considered 3679 molecular descriptors the relative value of lipoaffinity index, expressed as the difference between values calculated for active compound and excipient, has been found as the most appropriate measure suited for discrimination of positive and negative cases. Assuming 5% precision, the applied classification criterion led to inclusion of 70% positive cases in the final prediction. Since lipoaffinity index is a molecular descriptor computed using only 2D information about a chemical structure, its estimation is straightforward and computationally inexpensive. The inclusion of an additional criterion quantifying the cocrystallization probability leads to the following conjunction criterions H<-0.18 and ΔLA>3.61, allowing for identification of dissolution rate enhancers. The screening procedure was applied for finding the most promising coformers of such drugs as Iloperidone, Ritonavir, Carbamazepine and Enthenzamide.

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“…Una estrategia útil para predecir la polaridad de manera más acertada es combinar el cálculo del área de superficie polar con descriptores numéricos cuantitativos como VolSurf. Estos descriptores son extraídos de mapas de campos moleculares (calculados a partir de la configuración espacial de la molécula) [33,34].…”

Section: La Estructura Molecular Y Su Importancia En El Descubrimientunclassified

Descubrimiento de fármacos basado en imagenología de células vivas

Hernández-Cuellar

Martinez

Gallego-Gómez

2020

Rev. Colomb. Cienc. Quím. Farm.

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El diseño eficiente de compuestos aprovechando las características estructurales de las moléculas y la búsqueda eficiente de dianas terapéuticas, ha proporcionado herramientas efectivas en la investigación de nuevos tratamientos cuando esta se enfoca en mecanismos celulares de la enfermedad. Los cambios fenotípicos producidos por la interacción in vitro entre molécula-diana, pueden controlarse cuantitativamente mediante imagenología de células vivas. Para garantizar una interacción adecuada, es necesario considerar diferentes elementos cruciales: 1. Las características estructurales y la dinámica molecular del compuesto a evaluar. 2. La relevancia del blanco para la fisiopatología de interés. Sin embargo, el desconocimiento del panorama general en el descubrimiento de fármacos, desde problemáticas estructurales y celulares, ha enlentecido la búsqueda de nuevos tratamientos. Esta revisión descriptiva de tema presenta algunos aspectos estructurales importantes para la caracterización de compuestos como candidatos terapéuticos, y aproximaciones experimentales para desarrollo de sistemas celulares. Los tópicos discutidos se enfocan en la monitorización por imagenología de células vivas y así mismo proporcionamos ejemplos relevantes. La monitorización de efectos fenotípicos producidos por interacciones entre candidato químico y blanco terapéutico en un sistema celular puede favorecer la búsqueda eficiente de moléculas potencialmente terapéuticas.

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Surface area, volume and shape descriptors as a novel tool for polymer lead design and discovery

Cited by 7 publications

References 27 publications

DFT and QSAR Studies of Ethylene Polymerization by Zirconocene Catalysts

DFT and QSAR Studies of Ethylene Polymerization by Zirconocene Catalysts

Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index

Descubrimiento de fármacos basado en imagenología de células vivas

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