Nanostructure Empowers Active Tumor Targeting in Ligand‐Based Molecular Delivery

Cell‐selective targeting is expected to enhance effectiveness and minimize side effects of cytotoxic agents. Functionalization of drugs or drug nanoconjugates with specific cell ligands allows receptor‐mediated selective cell delivery. However, it is unclear whether the incorporation of an efficient ligand into a drug vehicle is sufficient to ensure proper biodistribution upon systemic administration, and also at which extent biophysical properties of the vehicle may contribute to the accumulation in target tissues during active targeting. To approach this issue, structural robustness of self‐assembling, protein‐only nanoparticles targeted to the tumoral marker CXCR4 is compromised by reducing the number of histidine residues (from six to five) in a histidine‐based architectonic tag. Thus, the structure of the resulting nanoparticles, but not of building blocks, is weakened. Upon intravenous injection in animal models of human CXCR4⁺ colorectal cancer, the administered material loses the ability to accumulate in tumor tissue, where it is only transiently found. It instead deposits in kidney and liver. Therefore, precise cell‐targeted delivery requires not only the incorporation of a proper ligand that promotes receptor‐mediated internalization, but also, unexpectedly, its maintenance of a stable multimeric nanostructure that ensures high ligand exposure and long residence time in tumor tissue.     

Sulla regolarità e irregolarità della frontiera per il primo problema di valori al contorno relativo all'equazione del calore

Sunto Sia D un dominio tipico relativo al primo problema di valori al contorno per l'equazione del calore. Nel presente lavoro si stabiliscono delle condizioni sufficienti di regolarità e delle condizioni sufficienti di irregolarità per i punti di quella porzione dellaFD su cui si assegnano i dati. A Mauro Picone nel suo 70^mo compleanno.     

Reactions of anionic porphyrin with group 11 elements: a spectrophotometric and electrospray ionization mass spectrometry study

The reaction of 3,8,13,18-tetramethyl-21H,23H-porphine-2,7,12,17-tetrapropionic acid or coproporphyrin-I (CPI) with the elements of 11 group have been studied. CPI is an anionic porphyrin that slowly reacts with copper ion to form Cu^IICPI and with silver ions to form Ag^IICPI, Ag^IIICPI complexes and colloidal silver. Gold ions do not form complexes with CPI, but, in the main, colloidal gold and some CPI-N-oxide. The kinetics of the reactions with copper and silver were spectrophotometerically studied and the rate constants were calculated. The identification and characterization of this water-soluble anionic porphyrin and its metal complexes have been performed by electrospray mass spectrometry (ESI-MS) that proved to be an excellent method for these determinations. The multiple charged parent ions for metal free ligand and their metal complexes were identified.     

Lévy statistics of vibrational mode fluctuations of single molecules from surface-enhanced Raman scattering

Surface-enhanced Raman spectra of a single Fe-protoporphyrin IX molecule display drastic fluctuations in frequency and intensity. When analyzed in their temporal evolution, the vibrational modes of the molecule undergo an on-off switching behavior that is shown to follow a Lévy statistics. Such a time dependent process may encode both the dynamics of the molecule-environment interactions and the intrinsic gating or activation of the mode emission mechanism.     

Phenomenological Λ-nuclear interactions

Variational Monte-Carlo calculations have been performed for the ligh s-shell hypernuclei, namely, _Λ ⁴ H, _Λ ⁴ H^*, and _Λ ⁵ He. The main aim of the study has been to give more insight into the Λ-nuclear interactions. Our study shows that the three-body ANN force has a larger share in the splitting energy of _Λ ⁴ H (0⁺–1⁺) compared to the two-body AN force. The analyses on Λ-binding to nuclear matter based on our s-shell results demonstrate that the three-body ANN correlations need to be incorporated suitably to describe these systems.     

Solid-state conformational heterogeneity of the 2,2,5,5-tetramethyl-3,4-hexandione monohydrazone: X-ray diffraction and MAS NMR experiments

The X-ray diffraction study of the 2,2,5,5-tetramethyl-3,4-hexandione mono-hydrazone 1 shows a solid solution of two screwed conformers in the crystal. In each of these conformers, the conjugated C=O and C=N double bonds have an approximately perpendicular orientation with = 101.1°(2) and –93.4°(2), respectively. AM1 theoretical calculations give the same result for the isolated molecule. The calculated rotational barrier around the central single bond of the conjugated moiety is about 45.98 kJ mol^–1 which is higher than the classical values observed for 1,3 conjugated systems (28.42 kJ mol^–1 in the 1,3-butadiene). Variable temperature ¹³C CPMAS NMR experiments show hindered rotation around the COC(CH₃)₃ tert-butyl group in the solid state. 1 crystallizes in the triclinic space group P ₁ with a = 10.106(1)Å, b = 11.698(1)Å, c = 12.313(1)Å, = 62.108(1)° = 70.517(1)° = 66.052(1), V = 1157.0(3)ų, D _calc = 1.06 with Z = 4.     

Effect of aqueous solvation on the structures of pyruvic acid isomers and their reactions in solution: a computational study

The pyruvic acid molecule and its various isomers have been studied in aqueous solution in order to understand the mechanism of decarboxylation. The tautomeric equilibrium remains in favor of the keto form in aqueous solution, but the energy difference between the two tautomers decreases. The anion also exists in the keto form in aqueous solution. Good agreement between the calculated and observed gas phase protonation and basicity values is obtained, and the calculated pK_a value is also in reasonable agreement with the literature value. The importance of the catalytic mechanism may be gauged from the fact that, in the absence of an enzymatic pathway, the reaction has high activation barrier and may not occur at all. Copyright © 2007 John Wiley & Sons, Ltd.