Solid form and solubility

Factors that determine the solubility of polymorphs and cocrystals are analysed using experimental data to show that the change in the solubility of a compound produced by the formation of a multicomponent crystal can be estimated in a straightforward manner, if the solubilities of the pure compound and the coformer are known

Canards, Folded Nodes, and Mixed-Mode Oscillations in Piecewise-Linear Slow-Fast Systems

Canard-induced phenomena have been extensively studied in the last three decades, from both the mathematical and the application viewpoints. Canards in slow-fast systems with (at least) two slow variables, especially near folded-node singularities, give an essential generating mechanism for mixed-mode oscillations (MMOs) in the framework of smooth multiple timescale systems. There is a wealth of literature on such slow-fast dynamical systems and many models displaying canard-induced MMOs, particularly in neuroscience. In parallel, since the late 1990s several papers have shown that the canard phenomenon can be faithfully reproduced with piecewise-linear (PWL) systems in two dimensions, although very few results are available in the three-dimensional case. The present paper aims to bridge this gap by analyzing canonical PWL systems that display folded singularities, primary and secondary canards, with a similar control of the maximal winding number as in the smooth case. We also show that the singular phase portraits are compatible in both frameworks. Finally, we show using an example how to construct a (linear) global return and obtain robust PWL MMOs

DNA structure directs positioning of the mitochondrial genome packaging protein Abf2p

The mitochondrial genome (mtDNA) is assembled into nucleo-protein structures termed nucleoids and maintained differently compared to nuclear DNA, the involved molecular basis remaining poorly understood. In yeast (Saccharomyces cerevisiae), mtDNA is a similar to 80 kbp linear molecule and Abf2p, a double HMG-box protein, packages and maintains it. The protein binds DNA in a non-sequence-specific manner, but displays a distinct 'phased-binding' at specific DNA sequences containing poly-adenine tracts (A-tracts). We present here two crystal structures of Abf2p in complex with mtDNA-derived fragments bearing A-tracts. Each HMG-box of Abf2p induces a 90. bend in the contacted DNA, causing an overall U-turn. Together with previous data, this suggests that U-turn formation is the universal mechanism underlying mtDNA compaction induced by HMG-box proteins. Combining this structural information with mutational, biophysical and computational analyses, we reveal a unique DNA binding mechanism for Abf2p where a characteristic N-terminal flag and helix are crucial for mtDNA maintenance. Additionally, we provide the molecular basis for A-tract mediated exclusion of Abf2p binding. Due to high prevalence of Atracts in yeast mtDNA, this has critical relevance for nucleoid architecture. Therefore, an unprecedented A-tract mediated protein positioning mechanism regulates DNA packaging proteins in the mitochondria, and in combination with DNA-bending and U-turn formation, governs mtDNA compaction

Combined virtual/experimental multicomponent solid forms screening of sildenafil: new salts, cocrystals, and hybrid salt-cocrystals

YesNew multicomponent solid forms of sildenafil have been discovered by means of a combined virtual/experimental cocrystal screening. Coformer selection of candidates was conducted based on an in silico screening method from a database of more than 2000 organic compounds, and the intensive experimental screen produced 23 new solid forms. Since the 12 coformers chosen have a combination of phenol and carboxylic acid groups, a variety of cocrystals, salts, and hybrid salt-cocrystals were discovered and characterized

The Ca2+-EDTA chelation as standard reaction to validate isothermal titration calorimeter measurements (ITC)

A study about the suitability of the chelation reaction of Ca2+with ethylenediaminetetraacetic acid (EDTA) as a validation standard for Isothermal Titration Calorimeter measurements has been performed exploring the common experimental variables (buffer, pH, ionic strength and temperature). Results obtained in a variety of experimental conditions have been amended according to the side reactions involved in the main process and to the experimental ionic strength and, finally, validated by contrast with the potentiometric reference values. It is demonstrated that the chelation reaction performed in acetate buffer 0.1 M and 25 °C shows accurate and precise results and it is robust enough to be adopted as a standard calibration proces

Global strategy for the conservation and use of eggplants

Common eggplant (Solanum melongena L.), also known as brinjal eggplant or aubergine, is a vegetable crop grown for its large soft fruits which are used in cooking. There are also two African eggplant species grown locally: scarlet eggplant (Solanum aethiop icum L.) and gboma eggplant (Solanum macrocarpon L.). According to the statistics of the United Nations Food and Agriculture Organization (FAO), eggplant is grown on 1.8 million hectares (ha) globally, and 90% of eggplant production takes place in Asia. Breeding and research on eggplant is carried out in many coun tries. Numerous germplasm collections of eggplant and its related species exist to provide plant materials for breeding and related research. In the present study, we overview the current status of eggplant germplasm conservation efforts and the use of eggplant diversity with the aim of providing a forward-looking strategy document. To do this, we surveyed the global databases Genesys and WIEWS (World Information and Early Warning System on Plant Genetic Resources for Food and Agriculture) to obtain information about existing eggplant ex situ collections. The most often represented species in these databases is brinjal eggplant with 12,715 acces sions conserved in total. This is followed by scarlet eggplant (886 accessions) and gboma eggplant (209 accessions). Wild relatives of eggplant are conserved in some collections, but some species are not well represented. In total, 109 eggplant collection holders were iden tified through the database searches. The collection holders were asked to complete an online survey on the status of their collections and the challenges that they faced. Responses were received from 32 collec tion holders, 27 of which provided sufficient data for further analyses. Most of the collection holders that responded were governmental organizations or publicly funded institutions. Two respondents were non-governmental organizations (NGOs). Several challenges related to the sustainability of eggplant conservation and use were identified. Shortages of funds and staff were reported as major threats to collection viability and security by many of the collec tion holders. Opportunities for improvement included recruiting new and/or young people interested in eggplant conservation, and increased collaborations across national borders and among institutions. Improved documentation of existing plant materials and increased information sharing were also identi fied as areas for improvement.publishedVersio

Modulation of reactivity in the cavity of liposomes promotes the formation of peptide bonds

In living cells reactions take place in membrane bound compartments, often in response to changes in the environment. Learning how the reactions are influenced by this compartmentalization will help us gain an optimal understanding of living organisms at the molecular level and, at the same time, will offer vital clues on the behavior of simple compartmentalized systems, such as prebiotic precursors of cells and cell-inspired artificial systems. In this work we show that a reactive building block (an activated amino acid derivative) trapped in the cavity of a liposome is protected against hydrolysis and reacts nearly quantitatively with another building block, which is membrane-permeable and free in solution, to form the dipeptide. By contrast, when found outside the liposome, the hydrolysis of the activated amino acid is the prevalent reaction, showing that the cavity of the liposomes promotes the formation of peptide bonds. We attribute this result to the large lipid concentration in small compartments from the point of view of a membrane-impermeable molecule. Based on this result we show how the outcome of the reaction can be predicted as a function of the size of the compartment. The implications of these results on the behavior of biomolecules in cell compartments, abiogenesis and the design of artificial cell-inspired systems are considere

Location of chlorogenic acid biosynthesis pathway and polyphenol oxidase genes in a new interspecific anchored linkage map of eggplant

© Gramazio et al.; licensee BioMed Central. 2014. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Genotype x environment interactions in eggplant for fruit phenolic acid content

Eggplant fruit are a rich source of phenolic acids that influence fruit culinary quality and antioxidant content. We evaluated the influence of production environments and stability of diverse genotypes across environments for eggplant fruit phenolic acid content. Ten Solanum melongena accessions consisting of five F-1 hybrid cultivars, three open-pollinated cultivars and two land race accessions, plus one S. macrocarpon and one S. aethiopicum accession, were grown at two locations under greenhouse and open field environments. Twenty phenolic acid conjugates were identified in fruit flesh and assigned to six classes that included hydroxycinnamic acid amides, caffeoylquinic acid esters, hydroxycinnamoylquinic acid esters, malonylcaffeoylquinic acid esters, di-hydroxycinnamoylquinic acid esters, and other hydroxycinnamic acid conjugates. There were significant differences among accessions for total phenolic acid conjugate content and for all six classes. There were no significant differences detected among the environments for any of the variables. However, the environment x accession interaction was highly significant for all phenolic acid classes. Broad-sense heritability estimates for all six phenolic acid classes were high, ranging from 0.64 to 0.96. Stability analysis demonstrated widespread instability for phenolic acid content across environments. Stability of the predominant caffeoylquinic acid esters class positively influenced stability of total phenolic acid content for some but not all genotypes. High heritability, coupled with highly significant genotype x environment interactions suggests that stability estimates may improve the efficiency of breeding new genotypes with predictable performance across environments.Stommel, JR.; Whitaker, B.; Haynes, K.; Prohens Tomás, J. (2015). Genotype x environment interactions in eggplant for fruit phenolic acid content. Euphytica. 205(3):823-836. doi:10.1007/s10681-015-1415-2S8238362053Allard RW, Bradshaw AD (1964) Implications of genotype–environment interactions in applied plant breeding. Crop Sci 4:503–507Baixauli C (2001) Berenjena. In: Nuez F, Liacer G (eds) La horticultura española. Ediciones de Horticultura, Reus, pp 104–108Bravo L (1998) Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 56:317–333Dixon RA, Pavia NL (1995) Stress-induced phenylpropanoid metabolism. Plant Cell 7:1085–1097Dogan M, Arslan O, Dogan S (2002) Substrate specificity, heat inactivation and inhibition of polyphenol oxidase from different aubergine cultivars. Int J Food Sci Technol 37:415–423Dos Santos MD, Almeida MC, Lopes NP, de Souza GE (2006) Evaluation of the anti-inflammatory, analgesic and anti-pyretic activities of the natural polyphenol chlorogenic acid. Biol Pharm Bull 29:2236–2240Fernandez GCJ (1991) Analysis of genotype × environment interaction by stability estimates. HortScience 26:947–950García-Salas P, Gómez-Caravaca AM, Morales-Soto A, Segura-Carretero A, Fernández-Gutiérrez A (2014) Identification and quantification of phenolic compounds in diverse cultivars of eggplant grown in different seasons by high-performance liquid chromatography coupled to diode array detector and electrospray-quadrupole-time of flight-mass spectrometry. Food Res Int 57:114–122Hanson PM, Yang RY, Tsou SCS, Ledesma K, Engle L, Lee TC (2006) Diversity in eggplant (Solanum melongena) for superoxide scavenging activity, total phenolics, and ascorbic acid. J Food Compos Anal 19:594–600Kang MS (1989) A new SAS program for calculating stability variance parameters. J Hered 80:415Klein RM (1990) Failure of supplementary ultraviolet radiation to enhance flower color under greenhouse conditions. HortScience 25:307–308Knapp SJ, Stroup WW, Ross WM (1985) Exact confidence intervals for heritability on a progeny mean basis. Crop Sci 25:192–194Luthria D, Singh AP, Wilson T, Vorsa N, Banuelos GS, Vinyard BT (2010) Influence of conventional and organic agricultural practices on the phenolic content in eggplant pulp: plant to plant variation. Food Chem 121:406–411Ma C, Whitaker BD, Kennelly EJ (2010) New 5-O-caffeoylquinic acid derivatives in fruit of wild eggplant relative S. viarum. J Agric Food Chem 58:9645–9651Manach C, Scalbert A, Morand C, Remesy C, Jimenez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747Mennella G, Scalzo R, Fibiani M, D’Alessandro A, Francese G, Toppino L, Acciarri N, Almeida AE, Rotino GL (2012) Chemical and bioactive quality traits during fruit ripening in eggplant (S. melongena L.) and allied species. J Agric Food Chem 60:11821–11831Meyer RS, Karol KG, Little DP, Nee MH, Litt A (2012) Phylogeographic relationships among Asian eggplants and new perspectives on eggplant domestication. Mol Phylogenet Evol 63:685–701Ong KW, Hsu A, Tan BK (2012) Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes. PLoS One 7:e32718Payyavula RS, Duroy AN, Kuhl JC, Pantoha A, Pillai SS (2012) Differential effects of environment on potato phenylpropanoid and carotenoid expression. BMC Plant Biol 12:39Plazas M, Prohens J, Cuñat AN, Vilanova S, Gramazio P, Herraiz FJ, Andújar I (2014) Reducing capacity, chlorogenic acid content and biological activity in a collection of scarlet (Solanum aethiopicum) and gboma (S. macrocarpon) eggplants. Int J Mol Sci 15:17221–17241Prior RL (2003) Fruits and vegetables in the prevention of cellular oxidative damage. Am J Clin Nutr 78:570S–578SPritts M, Luby J (1990) Stability indices for horticultural crops. HortScience 25:740–745Prohens J, Rodriguez-Burruezo A, Raigon MD, Nuez F (2007) Total phenolic acid concentration and browning susceptibility in a collection of different varietal types and hybrids of eggplant: implications for breeding for higher nutritional quality and reduced browning. J Am Soc Hortic Sci 132:638–646Prohens J, Whitaker BD, Plazas M, Vilanova S, Hurtado M, Blasco M, Gramazio P, Stommel JR (2013) Genetic diversity in morphological characters and phenolic acids content resulting from an interspecific cross between eggplant, Solanum melongena, and its wild ancestor (S. incancum). Ann Appl Biol 162:242–257Raigon MD, Prohens J, Munoz-Falcon JE, Nuez F (2008) Comparison of eggplant landraces and commercial varieties for fruit content of phenolics, minerals, dry matter and protein. J Food Compos Anal 21:370–376Raigon MD, Rodriguez-Burruezo A, Prohens J (2010) Effects of organic and conventional cultivation methods on composition of eggplant fruits. Agric Food Chem 58:6833–6840San Jose R, Sanchez-Mata MC, Camara M, Prohens J (2014) Eggplant fruit composition as affected by the cultivation environment and genetic constitution. J Sci Food Agric 94:2774–2784Sato Y, Itagaki S, Kurokawa T, Ogur J, Kobayashi M, Hirano T, Sugawara M, Iseki K (2011) In vitro and in vivo antioxidant properties of chlorogenic acid and caffeic acid. Int J Pharm 403:136–138Setimela PS, Vivek B, Banziger M, Crossa J, Maideni F (2007) Evaluation of early to medium maturing open pollinated maize varieties in SADC region using GGE biplot based on the SREG model. Field Crop Res 103:161–169Shukla GK (1972) Some statistical aspects of partitioning genotype environment components of variability. Heredity 29:237–245Stommel JR, Whitaker BD (2003) Phenolic acid content and composition of eggplant fruit in a germplasm core subset. J Am Soc Hortic Sci 128:704–710Suzuki A, Yamamoto N, Jokura H, Yamamoto M, Fujii A, Tokimitsu I, Saito I (2006) Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats. J Hypertens 24:1065–1073University of Maryland (2007) Commercial vegetable production recommendations, University of Maryland Cooperative Extension Service Bulletin 236. College Park, MDWhitaker BD, Stommel JR (2003) Distribution of hydroxycinnamic acid conjugates in fruit of commercial eggplant (Solanum melongena L.) cultivars. J Agric Food Chem 51:3448–3454Winter M, Herrmann K (1986) Esters and glucosides of hydroxycinnamic acids in vegetables. J Agric Food Chem 34:616–620Wu S, Meyer RS, Whitaker BD, Litt A, Kennelly EJ (2013) A New liquid chromatography-mass spectrometry-based strategy to integrate chemistry, morphology, and evolution of eggplant (Solanum) species. J Chromatogr A 1314:154–172Yang JS, Liu CW, Ma YS, Weng SW, Tang NY, Wu SH, Ji BC, Ma CY, Ko YC, Funayama S, Kuo CL (2012) Chlorogenic acid induces apoptotic cell death in U937 leukemia cells through caspase- and mitochondria-dependent pathways. In Vivo 26:971–97

Cocrystals of spironolactone and griseofulvin based on an in silico screening method

Cocrystal formation is considered as one of the most effective solid-state methods to alter the physicochemical properties of active pharmaceutical ingredients (APIs). In silico methods for cocrystal prediction are mostly based on structural and energetic considerations. We have developed a computational method that ranks the probability of cocrystal formation of APIs with large databases of crystal coformers (CCFs). This approach is based on using molecular electrostatic potential surfaces to assess molecular complementarity between two cocrystal components. The screening tool was applied to two low solubility drugs, namely griseofulvin and spironolactone. Promising coformer candidates were selected from a database of 310 pharmaceutically acceptable CCFs, and experimental screening was carried out. Novel solid forms were obtained by liquid-assisted grinding and were characterised by XRPD, DSC, TGA and IR. One new cocrystal of griseofulvin and two new cocrystals of spironolactone were identified, and the crystal structures were determined from the XRPD patterns. For these systems, phenols tend to act as successful H-bond donors in forming cocrystals, while carboxylic acids only give rise to physical mixtures of the two components