Characterization of crystalline and amorphous content in pharmaceutical solids by dielectric thermal analysis

Morphological and thermodynamic transitions in drugs as well as their amorphous and crystalline content in the solid state have been distinguished by thermal analytical techniques, which include dielectric analysis (DEA), differential scanning calorimetry (DSC), and macro-photomicrography. These techniques were used successfully to establish a structure versus property relationship with the United States Pharmacopeia standard set of active pharmaceutical ingredient (API) drugs. A distinguishing method is the DSC determination of the amorphous and crystalline content which is based on the fusion properties of the specific drug and its recrystallization. The DSC technique to determine the crystalline and amorphous content is based on a series of heat and cool cycles to evaluate the drugs ability to recrystallize. To enhance the amorphous portion, the API is heated above its melting temperature and cooled with liquid nitrogen to ?120 °C (153 K). Alternatively a sample is program heated and cooled by DSC at a rate of 10 °C min^?1. DEA measures the crystalline solid and amorphous liquid API electrical ionic conductivity. The DEA ionic conductivity is repeatable and differentiates the solid crystalline drug with a low conductivity level (10^?2 pS cm^?1) and a high conductivity level associated with the amorphous liquid (10⁶ pS cm^?1). The DSC sets the analytical transition temperature range from melting to recrystallization. However, analysis of the DEA ionic conductivity cycle establishes the quantitative amorphous and crystalline content in the solid state at frequencies of 0.10–1.00 Hz and to greater than 30 °C below the melting transition as the peak melting temperature. This describes the “activation energy method.” An Arrhenius plot, log ionic conductivity versus reciprocal temperature (K^?1), of the pre-melt DEA transition yields frequency dependent activation energy (E _a, J mol^?1) for the complex charging in the solid state. The amorphous content is inversely proportional to the E _a where the E _a for the crystalline form is higher and lower for the amorphous form with a standard deviation of ±2%. There was a good agreement between the DSC crystalline melting, recrystallization, and the solid state DEA conductivity method with relevant microscopic evaluation. An alternate technique to determine amorphous and crystalline content has been established for the drugs of interest based on an obvious amorphous and crystalline state identified by macro-photomicrography and compared to the conductivity variations. This second “empirical method” correlates well with the “activation energy” method.     

A label-free gold-nanoparticle-based SERS assay for direct cyanide detection at the parts-per-trillion level

Cyanide is an extremely toxic lethal poison known to humankind. Developing rapid, highly sensitive, and selective detection of cyanide from water samples is extremely essential for human life safety. Driven by the need, here we report a gold-nanoparticle-based label-free surface-enhanced Raman spectroscopy (SERS) system for highly toxic cyanide ion recognition in parts-per-trillion level and to examine gold-nanoparticle-cyanide interaction. We have shown that the SERS assay can be used to probe the gold nanoparticle dissociation process in the presence of cyanide ions. Our experimental data indicates that gold-nanoparticle-based SERS can detect cyanide from a water sample at the 110 ppt level with excellent discrimination against other common anions and cations. The results also show that the SERS probe can be used to detect cyanide from environmental samples.     

Octadecanuclear Gear Wheels by Self‐Assembly of Self‐Assembled “Double Saddle”‐Type Coordination Entities: Molecular “Rangoli”

A series of self‐assembled “double saddle”‐type trinuclear complexes of [Pd₃L′₃ L ₂] formulation have been synthesized by complexation of a series of cis‐protected palladium(II) components with a slightly divergent “E‐shaped” non‐chelating tridentate ligand, 1,1′‐(pyridine‐3,5‐diyl)bis(3‐(pyridin‐3‐yl)urea ( L ). The cis‐protecting agents L′ employed in the study are ethylenediamine (en), tetramethylethylenediamine (tmeda), 2,2′‐bipyridine (bpy), and 1,10‐phenanthroline (phen), for 1 , 2 , 3 , and 4 , respectively. The crystal structures of [Pd₃(tmeda)₃( L )₂](NO₃)₆ ( 2 ), [Pd₃(bpy)₃( L )₂](NO₃)₆ ( 3 ), and [Pd₃(phen)₃( L )₂](NO₃)₆ ( 4 ) unequivocally support the new architecture. Two of the “double saddle”‐type complexes ( 3 and 4 ) are suitably crafted with π surfaces at the strategically located cis‐protecting sites to facilitate intermolecular π–π interactions in the solid state. As a consequence, six units of the 3 (or 4 ) are assembled, by means of six‐pairs of π–π stacking interactions, in a circular geometry to form an octadecanuclear molecular ring of [(Pd₃L′₃ L ₂)₆] composition. The overall arrangement of the rings in the crystal packing is equated with the traditional Indian art form rangoli.