Syntheses of 5-hydroxy-2-(phenyl or styryl)chromones and of some halo derivatives

One-pot syntheses of 5-hydroxy-2-(phenyl or styryl)chromones and the corresponding 6- and 8-monoiodo- and 6,8-diiodochromones have been developed. The procedures involve oxidative cyclization of 2′-benzyloxy-6′-hydroxychalcones and 2′-benzyloxy-6′-hydroxy-2-cinnamylideneacetophenones and electrophilic substitution processes on the chromone moieties; such procedures were also applied to the syntheses of 6,8-dibromochromone derivatives.     

Design,Synthesis and Preclinical Assessment of 99mTc-iFAP for In Vivo Fibroblast Activation Protein (FAP) Imaging

Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. ⁶⁸Ga-labeled FAP inhibitors based on the cyanopyrrolidine structure (FAPI) are currently used for the detection of the tumor microenvironment by PET imaging. This research aimed to design, synthesize and preclinically evaluate a new FAP inhibitor radiopharmaceutical based on the ^99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (^99mTc-iFAP) structure for SPECT imaging. Molecular docking for affinity calculations was performed using the AutoDock software. The chemical synthesis was based on a series of coupling reactions of 6-hidrazinylnicotinic acid (HYNIC) and D-alanine to a boronic acid derivative. The iFAP was prepared as a lyophilized formulation based on EDDA/SnCl₂ for labeling with ^99mTc. The radiochemical purity (R.P.) was verified via ITLC-SG and reversed-phase radio-HPLC. The stability in human serum was evaluated by size-exclusion HPLC. In vitro cell uptake was assessed using N30 stromal endometrial cells (FAP positive) and human fibroblasts (FAP negative). Biodistribution and tumor uptake were determined in Hep-G2 tumor-bearing nude mice, from which images were acquired using a micro-SPECT/CT. The iFAP ligand (Ki = 0.536 nm, AutoDock affinity), characterized by UV-Vis, FT-IR, ¹H–NMR and UPLC-mass spectroscopies, was synthesized with a chemical purity of 92%. The ^99mTc-iFAP was obtained with a R.P. >98%. In vitro and in vivo studies indicated high radiotracer stability in human serum (>95% at 24 h), specific recognition for FAP, high tumor uptake (7.05 ± 1.13% ID/g at 30 min) and fast kidney elimination. The results found in this research justify additional dosimetric and clinical studies to establish the sensitivity and specificity of the ^99mTc-iFAP.     

Zwitterionic Cellulose Carbamate with Regioselective Substitution Pattern: A Coating Material Possessing Antimicrobial Activity

A polyzwitterion is synthesized by regioselective functionalization of cellulose possessing a uniform charge distribution. The positively charged ammonium group is present at position 6, while the negative charge of carboxylate is located at positions 2 and 3 of the repeating unit. The molecular structure of the biopolymer derivative is proved by NMR spectroscopy. This cellulose‐based zwitterion is applied to several support materials by spin‐coating and characterized by means of atomic force microscope, contact angle measurements, ellipsometry, and X‐ray photoelectron spectroscopy. The coatings possess antimicrobial activity depending on the support materials (glass, titanium, tissue culture poly(styrene)) as revealed by confocal laser scanning microscopy and live/dead staining.

     

Synthesis of a macrocycle based on Linked Amino Acid Mimetics (LAAM)

We report the synthesis of a macrocycle utilizing a novel framework of standard amino acids in combination with subunits that we have named as Linked Amino Acid Mimetics (LAAMs). Macrocycles based on the LAAM concept provide both a peptide targeting region and two independently variable functional regions. In the prototype structure, the commonly known Arg-Gly-Asp (RGD) sequence was used for the targeting region. The functional regions contain a phenyl group, and the linkage was formed via a Ring-Closing Metathesis (RCM) reaction.     

Multiscale Approach to the Study of the Electronic Properties of Two Thiophene Curcuminoid Molecules

We studied the electronic and conductance properties of two thiophene–curcuminoid molecules, 2‐thphCCM ( 1 ) and 3‐thphCCM ( 2 ), in which the only structural difference is the position of the sulfur atoms in the thiophene terminal groups. We used electrochemical techniques as well as UV/Vis absorption studies to obtain the values of the HOMO–LUMO band gap energies, showing that molecule 1 has lower values than 2 . Theoretical calculations show the same trend. Self‐assembled monolayers (SAMs) of these molecules were studied by using electrochemistry, showing that the interaction with gold reduces drastically the HOMO–LUMO gap in both molecules to almost the same value. Single‐molecule conductance measurements show that molecule 2 has two different conductance values, whereas molecule 1 exhibits only one. Based on theoretical calculations, we conclude that the lowest conductance value, similar in both molecules, corresponds to a van der Waals interaction between the thiophene ring and the electrodes. The one order of magnitude higher conductance value for molecule 2 corresponds to a coordinate (dative covalent) interaction between the sulfur atoms and the gold electrodes.     

Interplay of thermochemistry and Structural Chemistry, the journal (volume 23, 2012, issues 1–3) and the discipline

In the current review of the journal Structural Chemistry, the contents of the issues 1–3 for the calendar year 2012 are related to thermochemistry. A brief thermochemical commentary is added to the summary of each article.     

Dilute Ammonia Pretreatment of Sorghum and Its Effectiveness on Enzyme Hydrolysis and Ethanol Fermentation

A new pretreatment technology using dilute ammonium hydroxide was evaluated for ethanol production on sorghum. Sorghum fibers, ammonia, and water at a ratio of 1:0.14:8 were heated to 160 °C and held for 1 h under 140–160 psi pressure. Approximately, 44% lignin and 35% hemicellulose were removed during the process. Hydrolysis of untreated and dilute ammonia pretreated fibers was carried out at 10% dry solids at an enzyme concentration of 60 FPU Spezyme CP and 64 CBU Novozyme 188/g glucan. Cellulose digestibility was higher (84%) for ammonia pretreated sorghum as compared to untreated sorghum (38%). Fermentations with Saccharomyces cerevisiae D₅A resulted in 24 g ethanol /100 g dry biomass for dilute ammonia pretreated sorghum and 9 g ethanol /100 g dry biomass for untreated sorghum.