Massimiliano Cordaro

Diastereoselective multicomponent synthesis and anti-HSV-1 evaluation of dihydrofuran-fused derivatives

Enolizable 6-membered cyclic 1,3-dicarbonyls undergo an efficient and diastereoselective domino condensation/addition/heterocyclization reaction with arylaldehydes and phenacyl chloride, producing highly substituted dihydrofuran-fused derivatives. Ring size of the cyclic 1,3-dicarbonyls and the presence of at least one keto group are crucial to the reaction’s success. The new compounds were evaluated in vitro for antiviral activity against herpes simplex virus type-1 (HSV-1). Interestingly, some of them appeared able to interfere with HSV-1 replication, without detection of cytotoxic effects.

Synthesis and anti HSV-1 evaluation of novel indole-3,4-diones

A novel class of water soluble indole-3,4-diones has been synthesized and evaluated in vitro for antiviral activity against HSV-1. The results showed lack of cytotoxicity and significant antiviral activity. The cellular internalization efficiency and the antiherpetic effect were successfully increased by incorporation into nanoaggregates of an amphiphilic β-cyclodextrin.

Direct synthesis of C3-mono-functionalized oxindoles from N-unprotected 2-oxindole and their antileishmanial activity.

A novel approach for the synthesis of unprecedented C3-mono-functionalized indolin-2-ones is reported, starting from 2-oxindole and chalcones. The reactions proceed regioselectively under mild conditions, without di- and tri-alkylated side products. The new compounds have been evaluated in vitro for their antiproliferative effects against the protozoan Leishmania infantum. Interestingly, they appear able to kill L. infantum promastigotes and amastigotes, without significant cytotoxic effects.

Self-Catalyzed Mannich-Type Reaction of Enolizable Cyclic 1,3-Dicarbonyls to Acyclic Nitrones: An Entry to Functionalized β-Enamino Diones

A new method for the preparation of highly functionalized β-enamino diones has been developed. The protocol involves an initial self-catalyzed Mannich-type reaction of enolizable cyclic 1,3-dicarbonyls to nitrones, followed by a spontaneous intramolecular reorganization of the resulting nonisolated hydroxylamine to enamino derivatives. These compounds retain the features of unnatural α-amino acids. The ease of preparation makes them attractive intermediates for the synthesis of peptidomimetics, polyheterocycles, and other multifunctional compounds. All experimental results have been efficiently rationalized by in silico studies at the M06-2X level of theory, and a valid mechanistic pathway has been proposed.

Aldol-type compounds from water-soluble indole-3,4-diones: synthesis, kinetics, and antiviral properties

A straightforward transformation of indole-3,4-diones is reported. The reaction feasibility is evidenced by kinetic studies on a model substrate, revealing a double phase process with a first faster pseudo-first-order step (i.e., deprotonation of the dione and self-nucleophilic attack of the anion) and a subsequent slower dehydration of the intermediate. The overall process is faster at pH higher than the pK value of the investigated substrate. The biological relevance of new compounds has been assessed in vitro against herpes simplex virus type-1 (HSV-1), showing a more promising biological profile with respect to their precursors.

Structural Studies of a N‐[(N‐Unsubstituted Pyrrole‐3‐carbonyl)oxy]benzamide and its Precursor Spiro[isoxazole‐4,3′‐pyrrole]

The structures of 6-methyl-4,8,9-triphenyl-2-oxa-3,7-diazaspiro[4.4]nona-3,6-dien-1-one (3) and N-[(2-Methyl-4,5-diphenyl-1H-pyrrole-3-carbonyl)oxy]benzamide (4) were established by X-ray crystal-structure analysis. A significant improvement in the procedure currently available for the synthesis of these compounds is described. Ab initio and DFT calculations were carried out on the compound 4 and its precursor 3, and compared with X-ray results. In particular, to relate structural features to biological properties, the conformational characteristics and rotational barrier of compound 4 were studied.

High resolution electrospray and electrospray tandem mass spectra of rotenone and its isoxazoline cycloadducts.

An evaluation of the gas-phase ion chemistry of rotenone (1) by electrospray ionisation (ESI) mass spectrometry (MS) and tandem mass spectrometry (MS2) is presented, aiming at providing tools for its determination in natural and biological matrices. The behaviour of its cycloadducts with benzonitrile-N-oxide (2) and 2,4,6-trimethylbenzonitrile-N-oxide (3) was also evaluated and the MS data thus obtained have provided evidence into the mechanism of formation of the key product ion at m/z 192 which can be considered a marker in the MS and MS2 spectra of rotenone and its derivatives.

On the complexation of metal cations with “pure” diethylenetriamine-N,N,N′,N′′,N′′-pentakis(methylenephosphonic) acid

The complex formation between a series of biologically, environmentally, and technologically relevant cations (namely Sn2+, Zn2+, Cu2+, Fe2+, Fe3+ and Al3+) and diethylenetriamine-N,N,N′,N′′,N′′-pentakis(methylenephosphonic) acid (DTPMPA) has been investigated in NaCl aqueous solutions at I = 0.1 and 0.3 mol dm−3 and T = 298.15 K. The ligand used has been obtained in sufficient purity by a new efficient synthetic procedure for the determination of accurate and reliable data on its acid–base properties and metal complex formation. The stability constants determined in this work under different experimental conditions have been then used to assess the speciation of many systems containing the above-cited cations, and to quantify the sequestering ability of DTPMPA toward them, by means of the calculation of several pL0.5 values under various conditions simulating those of many real systems where this chelant is employed as a cationic sequestrant. Finally, some 1H- and 31P-NMR studies have also been performed to gain a further insight into the binding mode of DTPMPA toward metal cations.

Two-Dimensional Electronic Spectroscopy Reveals Dynamics and Mechanisms of Solvent-Driven Inertial Relaxation in Polar BODIPY Dyes

In this work, we demonstrate the use of two-dimensional electronic spectroscopy (2DES) to study the mechanism and time scale of the femtosecond Stokes shift dynamics in molecules characterized by intramolecular charge transfer, such as distyryl-functionalized boron dipyrromethene (BODIPY) molecules. The obtained results demonstrate that 2DES allows clear and direct visualization of the phenomenon. The analysis of the 2D data in terms of 2D frequency–frequency decay associated maps provides indeed not only the time scale of the relaxation process but also the starting and the final point of the energy flow and the associated reorganization energy, identified by looking at the coordinates of a negative signature below the diagonal. The sensitivity of the 2DES technique to vibrational coherence dynamics also allowed the identification of a possible relaxation mechanism involving specific interaction between a vibrational mode of the dye and the solvent.

Facile synthesis of boronic acids on a BODIPY core with promising sensitivity towards polyols

An efficient strategy for the synthesis of o-((ethyl)aminomethyl) phenyl boronic acid anchored on a BODIPY core is reported. Kinetic studies highlight the association with diols and fructose; BODIPY fluorescence is quenched upon substrate binding, showing an unusual turn-off response.