Conformational analysis of novel monoaryl substituted protoporphyrins by 1D NOE, 2D NOESY and molecular modeling studies

Porphyrins 1–4 are monoaryl protoporphyrins substituted on C-5 or C-15 by a phenyl group. One- and two-dimensional nOe experiments and molecular modeling studies allowed us to find the most favorable conformations for these compounds. In the four porphyrins, the exocyclic phenyl group adopts a non-coplanar disposition relative to the plane of the macrocycle and this is reflected in the ID nOe difference and 2D NOESY results. In porphyrins 1 and 3 the macrocycle is nearly planar while nonplanar saddle conformations were obtained for porphyrins 2 and 4.     

Structure of diaqua(itaconato) cadmium(II), [Cd(C5H4O4)(OH2)2]

[Cd(C₅H₄O₄)(OH₂)₂] (1), crystallizes in the monoclinic system, space groupP2₁/n, with lattice parametersa=7.323(2),b=16.028(6),c=7.202(2) Å, β=113.11(1)°, andZ=4. The Cd atom coordinates to seven oxygens in a monocapped trigonal antiprism fashion. The antiprisms share one vertex to form chains which run approximately parallel to thec axis. The itaconate ligands link the chains to form layers which stack along theb axis.     

Evaporation studies on sodium dehydrocholate aqueous solutions

The evaporation through the air/solution interface of sodium dehydrocholate (NaDHC) aqueous solutions was studied by surface tension and microbalance measurements. The evaporation rate was related to the aggregation processes in the bulk, but not with the adsorption monolayer compactness. Except for very dilute solutions the air/solution interface was saturated by NaDHC molecules, giving rise to a strongly nonideal monolayer. At very low concentration, the adsorbed monolayer behaved as an ideal two-dimensional gas. The results were in agreement with previous research results.     

Barrier to enantiomerization of unstabilized, chelated, and dipole-stabilized 2-lithiopyrrolidines

Kinetics experiments have been used to establish the free energy, enthalpy, and entropy of activation for the enantiomerization of three structural classes of 2-lithiopyrrolidines. We find that alpha-aminoorganolithiums chelated by a N-methoxyethyl or N-Boc group have a barrier to enantiomerization (DeltaG++) 2-3 kcal/mol lower than that of unstabilized alpha-aminoorganolithiums at 273 K. Density functional calculations were performed to clarify possible ground state and transition structures and to identify possible pathways for inversion of these chiral organolithium species.     

Selective synthesis of monoaryl substituted porphyrins

A synthetic route to meso-monoarylporphyrins using a MacDonald-type 2 + 2 condensation is described. In this method a bisformyl substituted dipyrrylmethane is treated with a biscarboxydipyrrylmethane. The 5-aryldipyrrylmethanes 15, 25 and 27 were obtained by condensation of the corresponding pyrroles 18, 28 and 29 respectively with benzaldehyde in presence of p-toluenesulfonic acid.     

Cyclopentene carbocyclic nucleosides related to the antitumor nucleoside clitocine and their conversion to 8-Aza-neplanocin analogues. Synthesis and antiviral activity

Synthesis of the cyclopentene carbocyclic analogue of the naturally occurring nucleoside clitocine ( 1 ) is reported. Starting with racemic cyclopentenylamine ( 10 ), the heterocyclic moieties of the clitocine analogue 4 and related 1,6-dihydro-6-oxo, 5 , and 2-amino-1,6-dihydro-6-oxo, 6 , analogues were constructed. These compounds were respectively converted to 8-aza-neplanocin A (7) , 8-aza-neplanocin D ( 8 , the inosine analogue), and the corresponding 8-aza-guanosine analogue 9 after reduction of the nitro group followed by nitrous acid cyclization. Extensive antiviral evaluation revealed that only 8-aza-neplanocin A ( 7 ) had enough antiviral activity to warrant further studies. This compound showed weak antiviral activity against HSV-1, HSV-20 and the thymidine kinase deficient (TK-) HSV-1. However, it displayed good antiviral activity against human cytomegalovirus (HCMV) at a concentration of 0.40–2.50 μg/ml, well below the cytotoxicity threshold. This activity profile is consistent with a mechanism of action involving the inhibition of the enzyme adenosylhomo-cysteine hydrolase.     

Advances and Perspectives in the Management of Varicella-Zoster Virus Infections

Varicella-zoster virus (VZV), a common and ubiquitous human-restricted pathogen, causes a primary infection (varicella or chickenpox) followed by establishment of latency in sensory ganglia. The virus can reactivate, causing herpes zoster (HZ, shingles) and leading to significant morbidity but rarely mortality, although in immunocompromised hosts, VZV can cause severe disseminated and occasionally fatal disease. We discuss VZV diseases and the decrease in their incidence due to the introduction of live-attenuated vaccines to prevent varicella or HZ. We also focus on acyclovir, valacyclovir, and famciclovir (FDA approved drugs to treat VZV infections), brivudine (used in some European countries) and amenamevir (a helicase-primase inhibitor, approved in Japan) that augur the beginning of a new era of anti-VZV therapy. Valnivudine hydrochloride (FV-100) and valomaciclovir stearate (in advanced stage of development) and several new molecules potentially good as anti-VZV candidates described during the last year are examined. We reflect on the role of antiviral agents in the treatment of VZV-associated diseases, as a large percentage of the at-risk population is not immunized, and on the limitations of currently FDA-approved anti-VZV drugs. Their low efficacy in controlling HZ pain and post-herpetic neuralgia development, and the need of multiple dosing regimens requiring daily dose adaptation for patients with renal failure urges the development of novel anti-VZV drugs.     

Synthesis, FTIR, solid-state NMR and SEM studies of novel polyampholytes or polyelectrolytes obtained from EGDE, MAA and imidazoles

Novel materials with either polyampholyte or polyelectrolyte character and coordination properties were obtained by reaction of methacrylic acid (MAA), imidazole (IM) or 2-methylimidazole (2MI) and ethylene glycol diglycidyl ether (EGDE) in the presence of benzoyl peroxide.This new synthetic strategy gave rise to non-soluble, compact plastics that can be milled into non-porous particles.The polymers were studied by solid-state ¹³C NMR spectroscopy, FT IR and scanning electron microscopy (SEM).The experimental values of the isoelectric point (pI) were 6.04 ± 0.02 for poly(EGDE-MAA-IM) and 6.4 ± 0.2 for poly(EGDE-MAA-2MI). The water content was low due to the high cross-linking degree.These materials behaved as ionic exchangers. Copper (Cu²⁺) was chosen as a model, the equilibrium binding was analyzed, and the coordination properties were studied by FTIR and scanning electron microscopy/energy dispersive X-ray analysis (SEM/EDS).The maximum binding capacity for copper ion was 67 mg g⁻¹ for poly(EGDE-MAA-IM), 57 mg g⁻¹ for poly(EGDE-MAA-2MI) and 0.9 mg g⁻¹ for poly(EGDE-MAA).     

New Mixed Ligand Organotellurium(IV) Compounds Containing Dithiocarbamates and the More Flexible Imidotetraphenyldithiodiphosphinates. The Crystal Structures of C8H8Te(S2CNEt2)[(SPPh2)2N] · H2O,C8H8Te(S2CNC5H10)[(SPPh2)2N], and C8H8Te(S2CNC4H8S)[(SPPh2)2N]

The synthesis of the following mixed ligand organotellurium(IV) compounds C₈H₈Te(S₂CNEt₂)[(SPPh₂)₂N] · H₂O ( 1 ), C₈H₈Te(S₂CNC₅H₁₀)[(SPPh₂)₂N] ( 2 ), C₈H₈Te(S₂CNC₄H₈O)[(SPPh₂)₂N] ( 3 ) and C₈H₈Te(S₂CNC₄H₈S)[(SPPh₂)₂N] ( 4 ) was achieved. They were characterized by IR, ¹H, ¹³C, ³¹P and ¹²⁵Te NMR, mass spectroscopy, and elemental analyses. The X‐ray crystal structures of 1 , 2 and 4 were determined. The both types of ligands display an asymmetrical chelating coordination mode on interaction with the tellurium atom. When these aniso‐bonded donor atoms are included in the coordination sphere, the tellurium atom exhibit an effective co‐ordination number of seven. The arrangement may be described as 1 : 2 : 2 : 2 coordination with a presumably stereoactive lone‐pair of electrons.     

Disposable Gold Electrode Array for Simultaneous Electrochemical Studies

An efficient and inexpensive eight gold electrode array has been manufactured by a combination of screen printing and gold electrodeposition techniques. Gold electrodeposition was performed in potentiostatic and galvanostatic conditions. Different treatments, involving temperature and polishing control, led to electrodes with different roughness. The electrochemical behavior of the generated gold surface was studied by cyclic voltammetry showing the characteristic response of polycrystalline gold, in contrast with disposable gold electrodes fabricated by screen printing from gold inks. The electrodes were chemically modified through the adsorption of alkanethiols self‐assembled monolayers and the coupling of a model protein. Both reactions were followed by cyclic voltammetry and Electrochemical Impedance Spectroscopy (EIS). The electrodes have shown high reproducibility in their electrochemical behavior as well as in their modifications.