6 research outputs found
Building Multivalent Iminosugar-Based Ligands on Calixarene Cores via Nitrone Cycloadditions
A novel and challenging approach for the construction
of multivalent
iminosugar architectures directly on calixarene scaffolds is presented,
which exploits multiple cycloaddition reactions of a carbohydrate-derived
nitrone on diversely functionalized calix[4]arenes. Regardless of
the 4-fold reiteration on a single calixarene, the reactions take
place with high regio- and stereoselectivity, demonstrating this method
as an appealing one for the synthesis of calixarene-based neoglycoconjugates
Ribonuclease Activity of an Artificial Catalyst That Combines a Ligated Cu<sup>II</sup> Ion and a Guanidinium Group at the Upper Rim of a <i>cone</i>-Calix[4]arene Platform
A <i>cone</i>-calix[4]arene derivative, featuring a guanidinium
group and a Cu<sup>II</sup> ion ligated to a 1,4,7-triazacyclononane
(TACN) ligand at the 1,3-distal positions of the upper rim, effectively
catalyzes the cleavage of 2-hydroxypropyl <i>p</i>-nitrophenyl
phosphate (HPNP) and a number of diribonucleoside 3′,5′-monophosphates
(<i>N</i>p<i>N</i>′). Kinetic and potentiometric
measurements support the operation of a general-base/general-acid
mechanism and demonstrate that the hydroxo form of the ligated Cu<sup>II</sup> ion is the sole catalytically active species. Rate enhancements
relative to the background hydrolysis reaction at 1 mM catalyst concentration
are 6 × 10<sup>5</sup>-fold for HPNP and cluster around 10<sup>7</sup>-fold with the most favorable catalyst–<i>N</i>p<i>N</i>′ combinations
Molecular Architecture and Symmetry Properties of 1,3-Alternate Calix[4]arenes with Orientable Groups at the Para Position of the Phenolic Rings
Two glycoclusters
constituted by four fully acetylated β-acetylmannosamine
residues linked through trimethylenethioureido spacers to a calix[4]arene
core and differing for the presence of methoxy or propoxy groups at
the lower rim were synthesized. One of the two compounds is fixed
in the 1,3-alternate geometry by the presence of the propoxy groups,
while the other is potentially free to assume one of the different
geometries allowed in calix[4]arene. Their similar NMR spectra in
chloroform clearly suggest the same 1,3-alternate geometry. Both compounds
were submitted to a conformational investigation with the DFT approach
at the standard B3LYP/6-31G(d) level. The two glycocalixarenes showed
a large conformational preference for the same geometry that put the
mannosamine moiety of one substituent close to the thioureido group
of the opposite substituent. This allows the formation of intramolecular
hydrogen bonds and originates a series of through-space close contacts.
A comparison with the NOESY maps evidence an excellent correspondence
between experimental and theoretical data, thus giving an experimental
validation of the highly symmetrical conformation that the two glycocalixarenes
assume in apolar solvents
Phosphonated Calixarene as a “Molecular Glue” for Protein Crystallization
Protein crystallization remains a
serious bottleneck to structure
determination by X-ray diffraction methods. Compounds acting as “molecular
glue” provide a promising strategy to overcome this bottleneck.
Such molecules interact via noncovalent bonds with two or more protein
surfaces to promote lattice formation. Here, we report a 1.5 Å
resolution crystal structure of lysine-rich cytochrome <i>c</i> complexed with <i>p</i>-phosphonatomethyl-calix[4]arene
(<b>pmclx</b><sub><b>4</b></sub>). Evidence for complex
formation in solution was provided by NMR studies. Similar to <i>p</i>-sulfonato-calix[4]arene (<b>sclx</b><sub><b>4</b></sub>), the cavity of <b>pmclx</b><sub><b>4</b></sub> entrapped a single lysine side chain. Interesting features of protein
recognition by the phosphonate substituents were identified in the
crystal structure. A new calixarene binding site was identified at
Lys54. The electron density at this site indicated two distinct calixarene
conformers, suggesting a degree of ligand mobility. The role of <b>pmclx</b><sub><b>4</b></sub> in protein crystal packing
(molecular glue and patchy particle model) as well as differences
in protein-binding with respect to <b>sclx</b><sub><b>4</b></sub> are discussed
Lower Rim Guanidinocalix[4]arenes: Macrocyclic Nonviral Vectors for Cell Transfection
Guanidinium groups were introduced through a spacer at
the lower
rim of calix[4]arenes in the cone conformation to give new potential
nonviral vectors for gene delivery. Several structural modifications
were explored, such as the presence or absence of a macrocyclic scaffold,
lipophilicity of the backbone, length of the spacer, and nature of
the charged groups, in order to better understand the factors which
affect the DNA condensation ability and transfection efficiency of
these derivatives. The most interesting compound was a calix[4]arene
unsubstituted at the upper rim and having four guanidinium groups
linked at the lower rim through a three carbon atom spacer. This compound,
when formulated with DOPE, showed low toxicity and transfection efficiency
higher than the commercially available lipofectamine LTX in the treatment
of human Rhabdomiosarcoma and Vero cells. Most of the investigated
compounds showed a tendency to self-aggregate in pure water or in
the presence of salts, as evidenced by NMR and AFM studies, and it
was found that the ability to condense DNA plasmids in nanometric
globules is a necessary but not sufficient condition for transfection.
The superiority of macrocyclic vectors over linear Gemini-type analogues
and of guanidinium compared to other ammonium head groups in determining
the biological activity of the vectors was also ascertained
Actinide–lanthanide co-extraction by rigidified diglycolamides
<p>Within the actinide and lanthanide co-extraction strategy, three rigidified diglycolamides, namely 2,6-bis (<i>N</i>-dodecyl-carboxamide)-4-oxo-4<i>H</i>-pyran (<b>1</b>), 2,6-bis-[<i>N</i>-(4-<i>tert</i>-butylphenyl)carboxamide]-4-oxo-4<i>H</i>-pyran (<b>2</b>), 2,6-bis[(<i>N</i>-docecyl-<i>N</i>-methyl)carboxamide]-4-methoxy-tetrahydro-pyran (<b>3</b>), were synthesized. Moreover, the effect of structural rigidification on Am(III) and Eu(III) extraction under different conditions was investigated. The carboxamide extractant <b>3</b> resembles the extracting behavior of <i>N,N,N</i>′,<i>N</i>′‐tetraoctyl diglycolamide (TODGA) in terms of efficiency and affinity within the lanthanide family, together with fast kinetics and satisfactory cation back-extraction. The presence of 1-octanol in the diluent mixture strongly affects the ligand stability. Moreover, despite the low extraction efficiency showed by <b>1</b> and <b>2</b>, all the three ligands exhibit a higher affinity for Am with respect to TODGA, resulting in a lower lanthanide/Americium separation factor, of around 4 for ligand <b>3</b> and close to 1 for ligands <b>1</b> and <b>2</b>.</p