Targeting EGFR Overexpression at the Surface of Colorectal Cancer Cells by Exploiting Amidated BODIPY-Peptide Conjugates

Three BODIPY-peptide conjugates designed to target the epidermal growth factor receptor (EGFR) at the extracellular domain were synthesized, and their specificity for binding to EGFR was investigated. Peptide sequences containing seven amino acids, GLARLLT ( 2) and KLARLLT ( 4 ), and 13 amino acids, GYHWYGYTPQNVI ( 3 ), were conjugated to carboxyl BODIPY dye ( 1 ) by amide bond formation in up to 73% yields. The BODIPY-peptide conjugates and their “parent” peptides were determined to bind to EGFR experimentally using SPR analysis and were further investigated using computational methods (AutoDock). Results of SPR, competitive binding and docking studies propose that conjugate 6 including the GYHWYGYTPQNVI sequence binds to EGFR more effectively than conjugates 5 and 7 , bearing the smaller peptide sequences. Findings in human carcinoma HEp2 cells overexpressing EGFR showed nontoxic behavior in the presence of activated light (1.5 J cm⁻²) and in the absence of light for all BODIPYs. Furthermore, conjugate 6 showed about five-fold higher accumulation within HEp2 cells compared with conjugates 5 and 7 , localizing preferentially in the cell ER and lysosomes. Our findings suggest that BODIPY-peptide conjugate 6 is a promising contrast agent for detection of colorectal cancer and potentially other EGFR-overexpressing cancers.     

From Open‐Shell Singlet Diradicaloid to Closed‐Shell Global Antiaromatic Macrocycles

A dithieno[a,h]‐s‐indacene‐ (DTI‐) based diradicaloid DTI‐2Br was synthesized and its open‐shell singlet diradical character was validated by magnetic measurements. On the other hand, its macrocyclic trimer DTI‐MC3 and tetramer DTI‐MC4 turned out to be closed‐shell compounds with global antiaromaticity, which was supported by X‐ray crystallographic analysis and NMR spectroscopy, assisted by ACID and 2D‐ICSS calculations. Such change can be explained by a subtle balance between two types of antiferromagnetic spin–spin coupling along the π‐conjugated macrocycles. The dications of DTI‐MC3 and DTI‐MC4 turned out to be open‐shell singlet diradical dications, with a singlet–triplet energy gap of ?2.90 and ?2.60 kcal mol^?1, respectively. At the same time, they are both global aromatic. Our studies show that intramolecular spin–spin interactions play important roles on electronic properties of π‐conjugated macrocycles.     

A modified set of Feynman postulates in quantum mechanics

Certain modifications, by way of improvement, are proposed for the Feynman postulates in quantum mechanics. These modifications incorporate a criterion for the applicability of the principle of superposition. It is shown that the modified postulates, together with certain assumptions regarding the trajectory of a particle, lead to an expression for the position-momentum uncertainty relationship which is broadly in agreement with the conventional expression. The time-energy uncertainty relationship is, however, found to have a likely place only in the relativistic theory. A criterion, in the form of a ratio involving the linear dimensions of the particle, is obtained for the validity of the classical mechanics approximation. The modified postulates are suggested to favor the statistical interpretation of quantum mechanics over the Copenhagen interpretation.     

Effect of Lithium Doping in the Bi-2212 Superconducting System

Samples with the nominal composition Bi₂Sr₂Ca_1–xLi_xCu₂O_y (x = 0.2,0.4, and 0.6) and Bi₂Sr₂CaCu_2−x L1_xO_z (x = 0.4, 0.6, and 1.0) were prepared by the solid state reaction method. The role of L1 at both Ca and Cu sites in the Bi-2212 composition were studied. From the X-ray diffraction data it was found that the L1-doped at the Ca site increases the c-axis and that doped at the Cu site decreases the c-axis. From the D.C. four-probe resistivity data it was found that Li-doped at the Ca site reduces the T_c and the L1-doped at the Cu site gives T_c(0) above the liquid nitrogen temperature. It was observed that the L1 doping reduces the melting point of Bi-2212 composition. The presence of Lithium was confirmed by inductive the coupled plasma method.     

Cyclobis(7,8‐(para‐quinodimethane)‐4,4′‐triphenylamine) and Its Cationic Species Showing Annulene‐Like Global (Anti)Aromaticity

π‐Conjugated macrocycles containing all‐benzenoid rings usually show local aromaticity, but reported herein is the macrocycle CBQT , containing alternating para‐quinodimethane and triphenylamine units displaying annulene‐like anti‐aromaticity at low temperatures as a result of structural rigidity and participation of the bridging nitrogen atoms in π‐conjugation. It was easily synthesized by intermolecular Friedel–Crafts alkylation followed by oxidative dehydrogenation. X‐ray crystallographic structures of CBQT , as well as those of its dication, trication, and tetracation were obtained. The dication and tetracation exhibited global aromaticity and antiaromaticity, respectively, as confirmed by NMR measurements and theoretical calculations. Both the dication and tetracation possess open‐shell singlet ground states, with a small singlet–triplet gap.     

Porphyrin/Quinoidal‐Bithiophene‐Based Macrocycles and Their Dications: Template‐Free Synthesis and Global Aromaticity

We report the template‐free synthesis and characterization of a new type of porphyrin/quinoidal‐bithiophene‐based conjugated macrocycle. X‐ray crystallographic analysis of the dimer ( 2MC ) revealed a cyclophane‐like geometry with large dihedral angles between the porphyrin and the neighboring thiophene rings, and NMR measurements and theoretical calculations confirmed a localized aromatic character of the porphyrin/thiophene rings and quinoidal character of the bithiophene linkers. Restricted rotation of the thiophene rings linked to the porphyrin unit was observed by variable‐temperature NMR measurements. The dication ( 2MC²⁺ ) adopts a chair‐shaped conformation to facilitate π‐electron delocalization around the whole macrocycle. As a result, the molecule is globally aromatic, with a dominant 54 π conjugation pathway. The trimer ( 3MC ) also shows localized aromatic character of porphyrin rings and conformational flexibility, but its dication ( 3MC²⁺ ) is rigid and globally aromatic with a dominant 82 π conjugation pathway.