Unraveling the Degradation Mechanism of Purine Nucleotides Photosensitized by Pterins: The Role of Charge‐Transfer Steps

Photosensitized reactions contribute to the development of skin cancer and are used in many applications. Photosensitizers can act through different mechanisms. It is currently accepted that if the photosensitizer generates singlet molecular oxygen (¹O₂) upon irradiation, the target molecule can undergo oxidation by this reactive oxygen species and the reaction needs dissolved O₂ to proceed, therefore the reaction is classified as ¹O₂‐mediated oxidation (type II mechanism). However, this assumption is not always correct, and as an example, a study on the degradation of 2′‐deoxyguanosine 5′‐monophosphate photosensitized by pterin is presented. A general mechanism is proposed to explain how the degradation of biological targets, such as nucleotides, photosensitized by pterins, naturally occurring ¹O₂ photosensitizers, takes place through an electron‐transfer‐initiated process (type I mechanism), whereas the contribution of the ¹O₂‐mediated oxidation is almost negligible.     

A new application of imprinted polymers: Speciation of organotin compounds

Molecular imprinting technology has been employed for the first time to prepare a specifically affinity chromatographic stationary phase for speciation purposes. Tributyltin has been chosen as the template molecule and the non-covalent approach has been applied. Three different polymerization methods have been evaluated: (i) a composite material, (ii) a polymer prepared via-Iniferter grafting; (iii) an emulsion polymer. Columns packed with different polymers have been evaluated by liquid chromatography (LC) coupled to inductively coupled plasma mass spectrometry (ICP-MS). The chromatographic conditions as well as the analytical characteristics of the developed method are discussed in this paper. Our findings have shown formation of specific cavities in the grafted Iniferter as well as in the emulsion polymers with the latter achieving resolution of four organotin compounds. Detection limits are similar to those obtained with commercial, but not specific, stationary phases (6 pg for monobutyltin, MBT; 10 pg for both tributyltin, TBT, and triphenyltin, TPhT; and 20 pg for dibutyltin, DBT). The main advantage of this proposed stationary phase is that good recovery is obtained for all species, including MBT. Baseline resolution for TBT and TPhT has also been obtained. The high selectivity of this column prevents matrix interferences. The method has been validated by analyzing two biota reference materials (ERM-CE477 mussel tissue and T-38 oyster tissue).     

An SFG/DFG investigation of CN− adsorption at an Au electrode in 1-butyl-1-methyl-pyrrolidinium bis(trifluoromethylsulfonyl) amide ionic liquid

In this paper we report an SFG/DFG investigation of the adsorption of CN^? – used as a probe molecule to study the electrochemical double-layer structure – at a polycrystalline Au electrode in 1-butyl-1-methyl-pyrrolidinium bis(trifluoromethylsulfonyl) amide ([BMP][TFSA]) room-temperature ionic liquid (RTIL). The adsorption of CN^? yielded single SFG and DFG bands in the range from ca. 2125 to 2135 cm^?1, exhibiting a Stark tuning of ca. 3 cm^?1 V^?1. Vibrational resonances – corresponding to modes of the RTIL coadsorbed with CN^?, were found in the range from ca. 1200 to 1500 cm^?1. The study of the double-layer structure was complemented by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements, from which the differential double-layer capacity (C_DL) was estimated.     

Dipyridylketone as a versatile ligand precursor for new cationic heteroleptic cyclometalated iridium complexes

Three new bis-cyclometalated iridium(III) complexes, of general formula [Ir(2-phenylpyridine)(2)(L)](+), are reported. The compounds contain a dipyridine-type ligand (L) derived from di-2-pyridylketone (dipyridin-2-ylmethanol, 2,2'-(hydrazonomethylene)dipyridine and 3-hydroxy-3,3-di(pyridine-2-yl)propanenitrile) and were synthesized through two different reaction pathways. The alternative synthetic pathway herein proposed, namely the direct reactions on the complex [Ir(2-phenylpyridine)(2)(2,2'-dipyridylketone)](+), overcame the inconveniences encountered with the standard reaction between the dimeric precursor [Ir(2-phenylpyridine)(2)(μ-Cl)](2) and the ancillary ligands (L). The photophysical characterization of the iridium complexes reveals that modifications on the ancillary ligand introduce large changes in the photophysical behaviour of the complexes. High emission quantum yield is associated with the presence of a saturated carbon between the two pyridyl moieties: [Ir(2-phenylpyridine)(2)(2,2'-dipyridylketone)](+) and [Ir(2-phenylpyridine)(2)(2,2'-(hydrazonomethylene)dipyridine)](+) are extremely low emissive, while [Ir(2-phenylpyridine)(2)(dipyridin-2-ylmethanol)](+) and [Ir(2-phenylpyridine)(2)(3-hydroxy-3,3-di(pyridine-2-yl)propanenitrile)](+) are good photoemitters. DFT and TD-DFT calculations confirmed the mixed LC/MLCT character of the excited states involved in the absorption and emission processes and highlighted the role of the π-conjugation between the two subunits of the ancillary ligand in determining the nature of the LUMO.     

A catalytic asymmetric reaction involving enolizable anhydrides

In the presence of a highly efficient novel bifunctional organocatalyst at low loadings under mild conditions, enolizable homophthalic anhydrides can be added to a range of aromatic and aliphatic aldehydes to give dihydroisocoumarins, with excellent yields and diastereo- and enantiocontrol (up to 99% ee).     

Understanding the role of base stacking in nucleic acids. MD and QM analysis of tandem GA base pairs in RNA duplexes

Preceding NMR experiments show that the conformation of tandem GA base pairs, an important recurrent non-canonical building block in RNA duplexes, is context dependent. The GA base pairs adopt "sheared" N3(G)-N6(A), N2(G)-N7(A) geometry in the r(CGAG)(2) and r(iGGAiC)(2) contexts while switching to "imino" N1(G)-N1(A), O6(G)-N6(A) geometry in the r(GGAC)(2) and r(iCGAiG)(2) contexts (iC and iG stand for isocytosine and isoguanine, respectively). As base stacking is likely to be one of the key sources of the context dependence of the conformation of GA base pairs, we calculated base stacking energies in duplexes containing such base pairs, to see if this dependence can be predicted by stacking energy calculations. When investigating the context dependence of the GA geometry two different conformations of the same duplex were compared (imino vs. sheared). The geometries were generated via explicit solvent MD simulations of the respective RNA duplexes, while the subsequent QM energy calculations focused on base stacking interactions of the four internal base pairs. Geometrical relaxation of nucleobase atoms prior to the stacking energy computations has a non-negligible effect on the results. The stacking energies were derived at the DFT-D/6-311++G(3df,3pd) level. We show a rather good correspondence between the intrinsic gas-phase stacking energies and the NMR-determined GA geometries. The conformation with more favorable gas-phase stacking is in most cases the one observed in experiments. This correlation is not improved when including solvent effects via the COSMO method. On the other side, the stacking calculations do not predict the relative thermodynamic stability of duplex formation for different sequences.     

Synthesis, 5-hydroxytryptamine1A receptor affinity and docking studies of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives

A series of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives (12a-h) was synthesized and evaluated for binding affinity at the human 5-hydroxytryptamine(1A) receptor (5-HT(1A)R) compounds (12b) and (12h) showed the highest 5-HT(1A) receptor affinity (IC(50)=15 nM). Molecular docking studies with all the compounds in a homology model of 5-HT(1A) showed that the main interaction anchoring the ligand in the receptor was a charge-reinforced bond between the protonated nitrogen atom (N-4) of the piperazine ring and Aspartate(3.32).     

Novel peptide foldameric motifs: a step forward in our understanding of the fully-extended conformation/3(10)-helix coexistence

The fully-extended, multiple C(5), conformation or 2.0(5) helix is a very appealing peptide secondary structure, in particular for its potential use as a molecular spacer, as it is characterized by the longest elevation (as high as 3.62 ?) between the α-carbon atoms of two consecutive α-amino acids. Despite this intriguing property, however, it is only poorly investigated and understood. Here, using a complete series of C(α,α)-diethylglycine (Deg) homo-oligopeptide esters to the pentamer level, we exploited the properties of a fluorophore and a quencher, synthetically positioned at the N- and C-termini of the main chain, respectively, to check the applicability of the fully-extended conformation as a rigid molecular spacer. The fluorescence study was complemented by FT-IR absorption and NMR conformational investigations. The X-ray diffraction structures of selected compounds are also reported. Unfortunately, we find that, even in a solvent of low polarity, such as chloroform, in this peptide series an equilibrium does take place between the fragile fully-extended conformation and the 3(10)-helical structure, the latter becoming more and more stable as the main chain is elongated. Since the Deg homo-peptide esters lacking any terminal aromatic group, previously investigated, are known to adopt a stable fully-extended conformation in chloroform solution, we tend to attribute the 3D-structure instability observed in this work to the presence of multiple aromatic rings in their blocking groups.     

Elasticity of flexible and semiflexible polymers with extensible bonds in the Gibbs and Helmholtz ensembles

Stretching experiments on single molecules of arbitrary length opened the way for studying the statistical mechanics of small systems. In many cases in which the thermodynamic limit is not satisfied, different macroscopic boundary conditions, corresponding to different statistical mechanics ensembles, yield different force-displacement curves. We formulate analytical expressions and develop Monte Carlo simulations to quantitatively evaluate the difference between the Helmholtz and the Gibbs ensembles for a wide range of polymer models of biological relevance. We consider generalizations of the freely jointed chain and of the worm-like chain models with extensible bonds. In all cases we show that the convergence to the thermodynamic limit upon increasing contour length is described by a suitable power law and a specific scaling exponent, characteristic of each model.