3 research outputs found
Postsynthetic Modification of Metal–Organic Frameworks through Nitrile Oxide–Alkyne Cycloaddition
Postsynthetic modification
of metal–organic frameworks is an important method to tailor
their properties. We report on the nitrile oxide–alkyne cycloaddition
(NOAC) as a modification tool, a reaction requiring neither strained
alkynes nor a catalyst. This is demonstrated with the reaction of
nitrile oxides with PEPEP-PIZOF-15 and -19 at room temperature. PIZOF-15
and -19 are porous Zr-based MOFs (BET surface areas 1740 and 960 m<sup>2</sup> g<sup>–1</sup>, respectively) consisting of two mutually
interpenetrating UiO-type frameworks with linkers of the type <sup>–</sup>O<sub>2</sub>CÂ[PE-PÂ(R<sup>1</sup>,R<sup>2</sup>)-EP]ÂCO<sub>2</sub><sup>–</sup> (P, phenylene; E, ethynylene; R<sup>1</sup> and R<sup>2</sup>, side chains at the central benzene ring with
R<sup>1</sup> = R<sup>2</sup> = OCH<sub>2</sub>Cî—¼CH or R<sup>1</sup> = OCH<sub>2</sub>Cî—¼CH and R<sup>2</sup> = OÂ(CH<sub>2</sub>CH<sub>2</sub>O)<sub>3</sub>Me). Their syntheses, using benzoic
acid as a modulator, and their characterization are reported herein.
The propargyloxy (OCH<sub>2</sub>Cî—¼CH) side chains contain
the ethyne moieties needed for NOAC. Formation of nitrile oxides through
oxidation of oximes in aqueous ethanolic solution in the presence
of PEPEP-PIZOF-15 and -19 resulted in the reaction of 96–100%
of the ethyne moieties to give isoxazoles. Thereby the framework was
preserved. The type of nitrile oxide RCNO was greatly varied with
R being isopentyl, tolyl, 2-pyridyl, and pentafluorophenyl. A detailed
NMR spectroscopic investigation showed the formation of the 3,5-disubstituted
isoxazole to be clearly favored (≥96%) over that of the constitutional
isomeric 3,4-disubstituted isoxazole, except for one example
Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis
Tumor
targeting anticancer drug conjugates that contain a tumor
recognition motif (homing device) are of high current relevance. Cryptophycins,
naturally occurring cytotoxic <i>cyclo</i>-depsipeptides,
have been modified by total synthesis to provide analogues suitable
for conjugation to peptide-based homing devices. An array of functionalized
β<sup>2</sup>-amino acids was synthesized and incorporated into
cryptophycins. All analogues proved to be highly active in the cytotoxicity
assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant
subclone KB-V1. Conformational analysis of cryptophycin-52 and two
synthetic analogues was performed by NMR and MD methods to obtain
information on the influence of the unit C configuration on the overall
conformation. An azide-functionalized cryptophycin was connected by
CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide
as the homing device for internalization studies. Confocal fluorescence
microscopy proved integrin-mediated internalization by endocytosis
and final lysosomal localization of the cryptophycin prodrug
Expanding the Group of Porous Interpenetrated Zr-Organic Frameworks (PIZOFs) with Linkers of Different Lengths
A Zr-based MOF of
the PIZOF type, which consists of two independent
and mutually interpenetrating UiO-type frameworks with [Zr<sub>6</sub>O<sub>4</sub>(OH)<sub>4</sub>(O<sub>2</sub>C)<sub>12</sub>] nodes,
does not only form with a PEPEP dicarboxylic acid (P = phenylene,
E = ethynylene). Also dicarboxylic acids with the shorter PPPP and
PEPP spacers were found to give PIZOFs, denoted PPPP-PIZOF and PEPP-PIZOF,
respectively. Reducing the spacer length even further to a PEEP segment
caused a switchover to the formation of a UiO framework. The hysteresis
in the Ar sorption curve of PEPP-PIZOF-1 and the slightly too large
amount of combustion residue from PPPP-PIZOF-1 suggest structural
defects. These hint at a mismatch between the requirement of the optimal
linker length for PIZOF formation and the lengths of the PEPP and
PPPP dicarboxylates. Nevertheless, these dicarboxylates prefer the
formation of a PIZOF over the formation of a UiO structure. PEPEP-PIZOF-2,
PPPP-PIZOF-1, and PEPP-PIZOF-1 are stable in air up to 325, 350, and
300 °C, respectively, and have BET surface areas of 2350, 2020,
and 1650 m<sup>2</sup> g<sup>–1</sup>, respectively. PEPEP-PIZOFs,
even those with very hydrophilic oligoÂ(ethylene glycol) side chains
on the linkers, are very stable in water and also during drying from
a water-wetted state. On the contrary, PEPP-PIZOF-1 and PPPP-PIZOF-1
that had been exposed to water required exchange of water for ethanol
before drying to mostly preserve the framework. The results emphasize
the importance of differentiating between framework damage caused
through hydrolysis in water and through drying from a water-wetted
state. The sensitivity of PEPP-PIZOF-1 and PPPP-PIZOF-1 against drying
from a water-wetted state may be the consequence of defects. The drying
stability of water-wetted PEPEP-PIZOFs lets us suggest that reversible
bending of the linkers contributes to the stability of the PEPEP-PIZOFs