Steering molecular organization and host-guest interactions using two-dimensional nanoporous coordination systems

Metal-organic coordination networks (MOCNs) have attracted wide interest because they provide a novel route towards porous materials that may find applications in molecular recognition, catalysis, gas storage and separation. The so-called rational design principle-synthesis of materials with predictable structures and properties-has been explored using appropriate organic molecular linkers connecting to metal nodes to control pore size and functionality of open coordination networks. Here we demonstrate the fabrication of surface-supported MOCNs comprising tailored pore sizes and chemical functionality by the modular assembly of polytopic organic carboxylate linker molecules and iron atoms on a Cu(100) surface under ultra-high-vacuum conditions. These arrays provide versatile templates for the handling and organization of functional species at the nanoscale, as is demonstrated by their use to accommodate C(60) guest molecules. Temperature-controlled studies reveal, at the single-molecule level, how pore size and chemical functionality determine the host-guest interactions.     

Comparison of a pair of synthetic tea-catechin-derived epimers: synthesis, antifolate activity, and tyrosinase-mediated activation in melanoma

Despite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin-derived compounds, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG), in an attempt to improve the stability and cellular absorption of tea polyphenols. The antiproliferative and pro-apoptotic activities of both compounds were analyzed with various cancer cell systems, and TMCG, which was easily synthesized in excellent yield, was more active than TMECG in both melanoma and non-melanoma cell lines. TMCG was also a better inhibitor of dihydrofolate reductase and was more efficiently oxidized by tyrosinase, potentially explaining the difference in activity between these epimers.     

Fumarate copolymers-based membranes overlooking future transdermal delivery devices: synthesis and properties

Novel copolymers of vinyl acetate and dialkylfumarates, poly(VA-co-DRF) with R = isopropyl (DIPF) or octan-2-yl (DOF), were synthesized by radical copolymerization under microwave conditions. The products were characterized by ¹H NMR and FTIR spectroscopies, size exclusion chromatography and differential scanning calorimetry. Based on these copolymers three membranes supported on polyvinyl alcohol were prepared and their morphology, swelling and mechanical properties were studied. The swelling kinetic was analyzed and interpreted in light of the Fick transport model, showing that the water transport occurs through a non-Fickian diffusion mechanism. The results show that the membrane prepared of poly(VA-co-DOF) exhibited excellent properties as potential platform for transdermal delivery system: they exhibited good tensile strength, moderated swelling and form thin and transparent films.     

Potential regulation by trophic factors of low-affinity NGF receptors in spinal motor neurons

Developing spinal motor neurons (SMN) express low-affinity nerve growth factor receptors (LNGFR) but not high-affinity transducing NGF receptors. Moreover, SMN are not supported by NGF in vitro. In the normal adult rat most SMN are not LNGFR immunoreactive (LNGFR-IR), but they transiently reexpress LNGFR (though not the high-affinity receptor) after peripheral nerve injury. With a cut lesion of the sciatic nerve (when only a neuroma forms), the number of LNGFR-IR SMN at L4-L6 rapidly increases to a maximum between day 1 and 7 and returns to baseline levels by day 30. After a crush lesion (accompanied by regeneration to the muscle), LNGFR-IR SMN appear in about the same numbers, but they start to disappear 1 week later. We speculate that the similar appearance and differential decline of LNGFR-IR seen after the two types of lesions are regulated by the availability of a common signal such as ciliary neurotrophic factor. The adult SMN model provides a good opportunity to investigate the reexpression of LNGFR after peripheral nerve injury, and more generally, the unknown role and regulation of LNGFR.     

Colloid transport in porous media: impact of hyper-saline solutions

The transport of colloids suspended in natural saline solutions with a wide range of ionic strengths, up to that of Dead Sea brines (10^0.9 M) was explored. Migration of microspheres through saturated sand columns of different sizes was studied in laboratory experiments and simulated with mathematical models.Colloid transport was found to be related to the solution salinity as expected. The relative concentration of colloids at the columns outlet decreased (after 2-3 pore volumes) as the solution ionic strength increased until a critical value was reached (ionic strength > 10^−1.8 M) and then remained constant above this level of salinity.The colloids were found to be mobile even in the extremely saline brines of the Dead Sea. At such high ionic strength no energetic barrier to colloid attachment was presumed to exist and colloid deposition was expected to be a favorable process. However, even at these salinity levels, colloid attachment was not complete and the transport of ∼30% of the colloids through the 30-cm long columns was detected.To further explore the deposition of colloids on sand surfaces in Dead Sea brines, transport was studied using 7-cm long columns through which hundreds of pore volumes were introduced. The resulting breakthrough curves exhibited a bimodal shape whereby the relative concentration (C/C₀) of colloids at the outlet rose to a value of 0.8, and it remained relatively constant (for the ∼18 pore volumes during which the colloid suspension was flushed through the column) and then the relative concentration increased to a value of one. The bimodal nature of the breakthrough suggests different rates of colloid attachment. Colloid transport processes were successfully modeled using the limited entrapment model, which assumes that the colloid attachment rate is dependent on the concentration of the attached colloids. Application of this model provided confirmation of the colloid aggregation and their accelerated attachment during transport through soil in high salinity solution.     

Binding of Natural and Synthetic Polyphenols to Human Dihydrofolate Reductase

Dihydrofolate reductase (DHFR) is the subject of intensive investigation since it appears to be the primary target enzyme for antifolate drugs. Fluorescence quenching experiments show that the ester bond-containing tea polyphenols (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) are potent inhibitors of DHFR with dissociation constants (K_D)of 0.9 and 1.8 μM, respectively, while polyphenols lacking the ester bound gallate moiety [e.g., (-)-epigallocatechin (EGC) and (-)-epicatechin (EC)] did not bind to this enzyme. To avoid stability and bioavailability problems associated with tea catechins we synthesized a methylated derivative of ECG (3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin; TMECG), which effectively binds to DHFR (K_D = 2.1 μM). In alkaline solution, TMECG generates a stable quinone methide product that strongly binds to the enzyme with a K_D of 8.2 nM. Quercetin glucuronides also bind to DHFR but its effective binding was highly dependent of the sugar residue, with quercetin-3-xyloside being the stronger inhibitor of the enzyme with a K_D of 0.6 μM. The finding that natural polyphenols are good inhibitors of human DHFR could explain the epidemiological data on their prophylactic effects for certain forms of cancer and open a possibility for the use of natural and synthetic polyphenols in cancer chemotherapy.     

Changes in PubMed affiliation indexing improved publication identification by country

Publications are often used to estimate the biomedical scientific production of an institution or country. Through its “affiliation” filter PubMed is a useful open-access tool for this purpose. In 2013 this filter was modified, beginning to include all authors. To estimate the impact of this modification we carried out the same search strategy before and after the change took place. We evaluated publications in PubMed from the 2010–2012 and 2014–2016 periods. Using the “affiliation” filter, we identified publications from three countries from different continents, with similar income level and number of scientific publications: Argentina, Thailand, and South Africa. We compared the slopes of both periods for each country and for the total references in PubMed. Regarding the number of publications, Argentina, Thailand and South Africa showed a significantly steeper slope in the 2014–2016 period versus 2010–2012 period, while the slopes of the total number of publications in PubMed showed no difference between periods. The inclusion of all authors in affiliation indexing by PubMed significantly impacts the evaluation of the scientific production of countries, reducing under-registration.