Stable 5,5′-Substituted 2,2′-Bipyrroles: Building Blocks for Macrocyclic and Materials Chemistry

The preparation and characterization of a family of stable 2,2′-bipyrroles substituted at positions 5 and 5′ with thienyl, phenyl, TMS-ethynyl, and vinyl groups is reported herein. The synthesis of these new bipyrroles comprises three steps: formation of the corresponding 5,5′-unsubstituted bipyrrole, bromination, and Stille or Suzuki coupling. The best results in the coupling are obtained using the Stille reaction under microwave irradiation. The new compounds have been fully characterized by UV–vis absorption, fluorescence, and IR spectroscopies and cyclic voltammetry. X-ray single-crystal analysis of four of the synthesized bipyrroles indicates a trans coplanar geometry of the pyrrole rings. Furthermore, the substituents at positions 5,5′ remain coplanar to the central rings. This particular geometry extends the π-conjugation of the systems, which is in agreement with a red-shifting observed for the λ_max of the substituted molecules compared to the unsubstituted bipyrrole. All of these new compounds display a moderate fluorescence. In contrast with unsubstituted bipyrroles, these bipyrroles are endowed with a high chemical and thermal stability and solubility in organic solvents

Quaterpyrroles as Building Blocks for the Synthesis of Expanded Porphyrins

A new family of quaterpyrroles and their application as building blocks for the synthesis of macrocycles is reported. The preparation of these quaterpyrroles consisted of two synthetic steps: bromination of 2,2′-bipyrroles bearing two electron-withdrawing groups followed by Suzuki coupling with 1-(<i>tert</i>-butoxy­carbonyl)­pyrrole-2-boronic acid. The resulting quaterpyrroles have been used to prepare an octaphyrin and a substituted cyclo[8]­pyrrole. Additionally, the synthesis of a new macrocycle containing the quaterpyrrole and 2,5-di­(1<i>H</i>-pyrrol-2-yl)­thio­phene moieties is presented

Quaterpyrroles as Building Blocks for the Synthesis of Expanded Porphyrins

A new family of quaterpyrroles and their application as building blocks for the synthesis of macrocycles is reported. The preparation of these quaterpyrroles consisted of two synthetic steps: bromination of 2,2′-bipyrroles bearing two electron-withdrawing groups followed by Suzuki coupling with 1-(<i>tert</i>-butoxy­carbonyl)­pyrrole-2-boronic acid. The resulting quaterpyrroles have been used to prepare an octaphyrin and a substituted cyclo[8]­pyrrole. Additionally, the synthesis of a new macrocycle containing the quaterpyrrole and 2,5-di­(1<i>H</i>-pyrrol-2-yl)­thio­phene moieties is presented

Synthesis, Characterization, and Photoinduced Antibacterial Activity of Porphyrin-Type Photosensitizers Conjugated to the Antimicrobial Peptide Apidaecin 1b

Antimicrobial photodynamic therapy (aPDT) is an emerging treatment for bacterial infections that is becoming increasingly more attractive because of its effectiveness against multi-antibiotic-resistant strains and unlikelihood of inducing bacterial resistance. Among the strategies to enhance the efficacy of PDT against Gram-negative bacteria, the binding to a cationic antimicrobial peptide offers the attractive prospect for improving both the water solubilty and the localization of the photoactive drug in bacteria. In this work we have compared a number of free and apidaecin-conjugated photosensitizers (PSs) differing in structure and charge. Our results indicate that the conjugation of per se ineffective highly hydrophobic PSs to a cationic peptide produces a photosensitizing agent effective against Gram-negative bacteria. Apidaecin cannot improve the phototoxic activity of cationic PSs, which mainly depends on a very high yield of singlet oxygen production in the surroundings of the bacterial outer membrane. Apidaecin–PS conjugates appear most promising for treatment protocols requiring repeated washing after sensitizer delivery

Modifications of Microvascular EC Surface Modulate Phototoxicity of a Porphycene anti-ICAM‑1 Immunoconjugate; Therapeutic Implications

Inflammation and shear stress can upregulate expression of cellular adhesion molecules in endothelial cells (EC). The modified EC surface becomes a mediating interface between the circulating blood elements and the endothelium, and grants opportunity for immunotherapy. In photodynamic therapy (PDT), immunotargeting might overcome the lack of selectivity of currently used sensitizers. In this study, we hypothesized that differential ICAM-1 expression modulates the effects of a drug targeted to surface ICAM-1. A novel porphycene–anti-ICAM-1 conjugate was synthesized and applied to treat endothelial cells from macro and microvasculature. Results show that the conjugate induces phototoxicity in inflamed, but not in healthy, microvascular EC. Conversely, macrovascular EC exhibited phototoxicity regardless of their state. These findings have two major implications; the relevance of ICAM-1 as a modulator of drug effects in microvasculature, and the potential of the porphycene bioconjugate as a promising novel PDT agent