4 research outputs found
Role of Steric Hindrance in the Newman-Kwart Rearrangement and in the Synthesis and Photophysical Properties of Arylsulfanyl Tetrapyrazinoporphyrazines
Conditions for the Newman-Kwart rearrangement
of phenols into thiophenols
were investigated in relation to the bulkiness of substituents at
the 2 and 6 positions of the starting phenol derivative with an emphasis
on eliminating side reactions. Thiophenols with different 2,6-disubstitution
patterns (including hydrogen, methyl, isopropyl or <i>tert</i>-butyl groups) were used for the synthesis of 5,6-bis(arylsulfanyl)pyrazine-2,3-dicarbonitriles
that underwent cyclotetramerization leading to the corresponding zinc
tetrapyrazinoporphyrazines (TPyzPz), aza-analogues of phthalocyanines.
Several methods for the cyclotetramerization were attempted to eliminate
problematic side reactions. Magnesium butoxide was found as the most
suitable cyclotetramerization agent and afforded TPyzPzs in reasonable
yields of approximately 30% under mild conditions. The varying arrangements
of the peripheral substitutions resulting from the different bulkiness
of the substituents were demonstrated by the X-ray structures of the
pyrazine-2,3-dicarbonitriles. The prepared zinc arylsulfanyl TPyzPzs
showed an absorption maximum at a Q-band over 650 nm, fluorescence
quantum yields between 0.078 and 0.20, and singlet oxygen quantum
yields ranging 0.58–0.69. TPyzPzs with isopropyl groups were
found to be the best derivatives in this series as they combined facile
cyclotetramerization, no aggregation, and good photophysical properties,
which makes them potentially suitable for photodynamic therapy
Role of Steric Hindrance in the Newman-Kwart Rearrangement and in the Synthesis and Photophysical Properties of Arylsulfanyl Tetrapyrazinoporphyrazines
Conditions for the Newman-Kwart rearrangement
of phenols into thiophenols
were investigated in relation to the bulkiness of substituents at
the 2 and 6 positions of the starting phenol derivative with an emphasis
on eliminating side reactions. Thiophenols with different 2,6-disubstitution
patterns (including hydrogen, methyl, isopropyl or <i>tert</i>-butyl groups) were used for the synthesis of 5,6-bis(arylsulfanyl)pyrazine-2,3-dicarbonitriles
that underwent cyclotetramerization leading to the corresponding zinc
tetrapyrazinoporphyrazines (TPyzPz), aza-analogues of phthalocyanines.
Several methods for the cyclotetramerization were attempted to eliminate
problematic side reactions. Magnesium butoxide was found as the most
suitable cyclotetramerization agent and afforded TPyzPzs in reasonable
yields of approximately 30% under mild conditions. The varying arrangements
of the peripheral substitutions resulting from the different bulkiness
of the substituents were demonstrated by the X-ray structures of the
pyrazine-2,3-dicarbonitriles. The prepared zinc arylsulfanyl TPyzPzs
showed an absorption maximum at a Q-band over 650 nm, fluorescence
quantum yields between 0.078 and 0.20, and singlet oxygen quantum
yields ranging 0.58–0.69. TPyzPzs with isopropyl groups were
found to be the best derivatives in this series as they combined facile
cyclotetramerization, no aggregation, and good photophysical properties,
which makes them potentially suitable for photodynamic therapy
Scalable Synthesis of Human Ultralong Chain Ceramides
Ceramides
with ultralong chains (≥30 carbons), also known
as acylceramides, play a critical role in the survival of mammals
on dry land. An efficient and scalable synthesis of four major classes
of ultralong human skin ceramides is reported. The key approach involves
the use of a succinimidyl ester that acts as a protective group, helps
overcome the extremely low solubility, and simultaneously activates
the fatty acid for its clean and high-yielding attachment to a sphingoid
base
Conventional-Flow Liquid Chromatography–Mass Spectrometry for Exploratory Bottom-Up Proteomic Analyses
Due
to its sensitivity and productivity, bottom-up proteomics based
on liquid chromatography–mass spectrometry (LC–MS) has
become the core approach in the field. The <i>de facto</i> standard LC–MS platform for proteomics operates at sub-μL/min
flow rates, and nanospray is required for efficiently introducing
peptides into a mass spectrometer. Although this is almost a “dogma”,
this view is being reconsidered in light of developments in highly
efficient chromatographic columns, and especially with the introduction
of exceptionally sensitive MS instruments. Although conventional-flow
LC–MS platforms have recently penetrated targeted proteomics
successfully, their possibilities in discovery-oriented proteomics
have not yet been thoroughly explored. Our objective was to determine
what are the extra costs and what optimization and adjustments to
a conventional-flow LC–MS system must be undertaken to identify
a comparable number of proteins as can be identified on a nanoLC–MS
system. We demonstrate that the amount of a complex tryptic digest
needed for comparable proteome coverage can be roughly 5-fold greater,
providing the column dimensions are properly chosen, extra-column
peak dispersion is minimized, column temperature and flow rate are
set to levels appropriate for peptide separation, and the composition
of mobile phases is fine-tuned. Indeed, we identified 2 835
proteins from 2 μg of HeLa cells tryptic digest separated during
a 60 min gradient at 68 μL/min on a 1.0 mm × 250 mm column
held at 55 °C and using an aqua–acetonitrile mobile phases
containing 0.1% formic acid, 0.4% acetic acid, and 3% dimethyl sulfoxide.
Our results document that conventional-flow LC–MS is an attractive
alternative for bottom-up exploratory proteomics