2,2'-Bipyridine Derivatives as Halogen Bond Acceptors in Multicomponent Crystals.

In this work, we present a systematic study of the halogen bonding potential of different 2,2'-bipyridine derivatives in the synthesis of cocrystals by using selected perfluorinated iodobenzenes and N-haloimides as halogen bond donors. These halogen bond acceptor molecules were chosen to explore how different substituents on 2,2'-bipyridine affect halogen bond formation. Out of 24 combinations, we obtained only 8 cocrystals by using two methods, liquid-assisted grinding and crystallization from the solution. Of those 8 cocrystals, one has already been described in the literature. As expected, structural data revealed that 2,2'-bipyridine derivatives act as ditopic halogen bond acceptors in all structures. Dominant interactions in 7 of the cocrystals are I···N or Br···N halogen bonds, while in the one remaining cocrystal it is the I···C(π) halogen bond.

Halogen and Hydrogen Bond Motifs in Ionic Cocrystals Derived from 3-Halopyridinium Halogenides and Perfluorinated Iodobenzenes.

Four halopyridinium salts, 3-chloro- and 3-bromopyridinium chlorides and bromides, have been successfully cocrystallized with two ditopic perfluorinated iodobenzenes, 1,4-diiodotetrafluorobenzene and 1,2-diiodotetrafluorobenzene. These halogen bond donor molecules were chosen because the different positionings of halogen bond donor atoms can lead to different supramolecular architectures. In this work, we present insight into the halogen bond acceptor potential of chloride and bromide ions, as well as the halogen bond donor potential of chlorine and bromine atoms substituted on the pyridinium ring when combined with the expectedly very strong hydrogen bonds between halopyridinium ions and free halogenide anions. A series of eight cocrystals were obtained in which three pairs of isostructural cocrystals were formed. Dominant interactions in the obtained cocrystals were charge-assisted hydrogen bonds between halopyridinium cations and halogenide ions as well as halogen bonds between halogen atoms on the pyridinium ring and halogenide ions.

Elucidating the effect of specific surface area on the gastrointestinal absorption of nanostructured calcium through Calcium-45 in vivo radiotracing.

Low dietary calcium intake and absorption may increase the risk of hypocalcaemia disease states. Reducing the particle size of calcium-containing powders and increasing the specific surface area (SSA), may have high oral calcium bioavailability. The absorption of a single dose of different sized calcium carbonate nanoparticles was traced in Sprague-Dawley rats with radioactive calcium-45 (half-life = 162.6 days, ß- endpoint = 258 keV; 100%). Four calcium carbonate formulations (calcium-45) were administered to Sprague-Dawley rodents (6 per treatment; n = 24). The groups were [45Ca]CaCO3 SSA 3 m2/g, [45Ca]CaCO3 36 m2/g, [45Ca]CaCO3 64 m2/g and a separate [45Ca]CaCO3 36 m2/g formulation produced by flame assisted pyrolysis. Blood and urine were sampled periodically, and organs collected and analysed after euthanasia. No changes in SSA or crystallinity were observed when powders before or after irradiation were compared. The [45Ca]CaCO3 64 m2/g formulation presented with higher levels in blood 2 h after administration and a higher liver and femur concentration. These findings suggest [45Ca]CaCO3 64 m2/g could lead to increased oral bioavailability.

Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron.

Iron-deficiency anaemia (IDA) is a major global public health problem. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods, but the most bioavailable fortificants cause adverse organoleptic changes in foods. Iron nanoparticles are a promising solution in food matrices, although their tendency to oxidize and rapidly aggregate in solution severely limits their use in fortification. Amyloid fibrils are protein aggregates initially known for their association with neurodegenerative disorders, but recently described in the context of biological functions in living organisms and emerging as unique biomaterial building blocks. Here, we show an original application for these protein fibrils as efficient carriers for iron fortification. We use biodegradable amyloid fibrils from ß-lactoglobulin, an inexpensive milk protein with natural reducing effects, as anti-oxidizing nanocarriers and colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms a stable protein-iron colloidal dispersion that undergoes rapid dissolution and releases iron ions during acidic and enzymatic in vitro digestion. Importantly, this hybrid shows high in vivo iron bioavailability, equivalent to ferrous sulfate in haemoglobin-repletion and stable-isotope studies in rats, but with reduced organoleptic changes in foods. Feeding the rats with these hybrid materials did not result in abnormal iron accumulation in any organs, or changes in whole blood glutathione concentrations, inferring their primary safety. Therefore, these iron-amyloid fibril hybrids emerge as novel, highly effective delivery systems for iron in both solid and liquid matrices.

Chemical Composition, but Not Specific Surface Area, Affects Calcium Retention of Nanostructured Calcium Compounds in Growing Rats.

Background: Low dietary calcium intake and bioavailability may adversely affect bone health. Reducing the size of calcium compounds increases their specific surface area (SSA, expressed as m2/g) and may increase calcium dissolution and bioavailability.Objective: We investigated the influence of SSA and chemical composition on the bioavailability of calcium and compared in vitro calcium dissolution with in vivo absorption.Methods: Calcium dissolution was measured in 0.1 M phosphoric acid, whereas color and pH changes of foods were assessed as indicators for potential sensory performance. Calcium absorption, retention, and fractional retention were measured over a 5-d balance study in growing Sprague-Dawley male rats after 21 d of feeding. Femoral and vertebral bone mineral density (BMD) and extensive tissue histology were assessed at study end. The influence of SSA on calcium bioavailability was assessed by comparing the groups fed pure calcium carbonate (CaCO3) with increasing SSAs of 3, 36, and 64 m2/g (CaCO3_3, CaCO3_36 and CaCO3_64), whereas chemical composition was assessed by comparing the smallest CaCO3_64, a 50:50 wt:wt percent solution mixture of CaCO3 and hydroxyapatite_94, and pure hydroxyapatite_100.Results: In vivo, fractional calcium retention from hydroxyapatite_100 (mean ± SEM: 54.86% ± 0.95%/5 d) was significantly greater than from CaCO3_64 (49.66% ± 1.15%/5 d) (P = 0.044). Increasing SSA of the pure CaCO3 did not significantly improve calcium retention. Across all 5 groups, there were no significant differences in BMD or tissue calcification by histology. In vitro calcium dissolution did not correlate with SSA or calcium absorption. In selected food matrixes, hydroxyapatite_100 caused less color change and/or smaller pH increase than did the other calcium compounds.Conclusions: Our findings suggest that chemical composition rather than SSA is a predictor of nanostructured calcium bioavailability and that in vitro dissolution of nanostructured calcium does not predict in vivo absorption. Although its phosphorus content may limit use in some populations, nanostructured hydroxyapatite may be a promising calcium compound for food fortification.