Several complexes of “PtL 2 ” composition containing two cyanoxime anions – 2-oximino-2-cyano- N -piperidineacetamide (PiPCO − ) and 2-oximino-2-cyano- N -morpholylacetamide (MCO − ) – have been obtained and characterized both in solution and in the solid state. Complexes exist as two distinct polymorphs: monomeric yellow complexes and dark-green [PtL 2 ] n 1D polymers, while for the MCO − anion a red, solvent containing dimeric [Pt(MCO) 2 ·DMSO] 2 complex has also been isolated. The interconversion of polymorphs was investigated. The monomeric PtL 2 units are arranged into anisotropic extended solid [PtL 2 ] n polymers with the help of Pt⋯Pt metallophilic interactions. Crystal structures of monomeric PtL 2 (L = PiPCO − , MCO − ) and red dimeric [Pt(MCO) 2 ·DMSO] 2 complexes were determined and revealed the cis -arrangement of cyanoxime anions. The Pt–Pt distance in the “head-to-tail” red dimer was found to be 3.133 Å. The structure of the polymeric [Pt(PiPCO) 2 ] n compound was elucidated using the EXAFS method and evidenced the formation of Pt-wires with ∼3.15 Å intermetallic separation. The EPR spectra of both 1D polymers at variable temperatures indicate the absence of Pt( iii ) species. Both pure dark-green [PtL 2 ] n polymers showed a considerable room temperature electrical conductivity of 20–30 S cm −1 , which evidences the formation of a mixed valence Pt( ii )/Pt( iv ) system. We discovered that these 1D polymeric [PtL 2 ] n complexes show an intense NIR fluorescence beyond 1000 nm, while yellow monomeric PtL 2 complexes are not emissive at all. The room temperature excitation spectra of 1D polymeric [PtL 2 ] n complexes demonstrated their strong emission beyond 1000 nm regardless of the used excitation wavelength between 350 and 800 nm, which is typical of systems with delocalized charge carriers. For the first time the formation of mixed valence “metal wires” held together by metallophilic interactions is directly linked both with an intense fluorescence in the NIR region of the spectrum and with the electrical conductivity. The effect of the concentration of [PtL 2 ] n complexes dispersed in the dielectric salt matrix on the photoluminescence wavelength and intensity was investigated. Both polymers show a quantum yield that is remarkably high for this region of the spectrum, reaching ∼2%. Variable temperature emission of polymeric [PtL 2 ] n in the −190–+60 °C range was studied as well.
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Stability of Protein Structure during Nanocarrier Encapsulation: Insights on Solvent Effects from Simulations and Spectroscopic Analysis
ABSTRACT: The dosing of peptide and protein therapeutics is complicated by rapid
clearance from the blood pool and poor cellular membrane permeability. Encapsulation
into nanocarriers such as liposomes or polymersomes has long been explored to
overcome these limitations, but manufacturing challenges have limited clinical translation
by these approaches. Recently, inverse Flash NanoPrecipitation (iFNP) has been
developed to produce highly loaded polymeric nanocarriers with the peptide or protein
contained within a hydrophilic core, stabilized by a hydrophobic polymer shell.
Encapsulation of proteins with higher-order structure requires understanding how processing may affect their conformational
state. We demonstrate a combined experimental/simulation approach to characterize protein behavior during iFNP processing
steps using the Trp-cage protein TC5b as a model. Explicit-solvent fully atomistic molecular dynamics simulations with
enhanced sampling techniques are coupled with two-dimensional heteronuclear multiple-quantum coherence nuclear
magnetic resonance spectroscopy (2D-HMQC NMR) and circular dichroism to determine the structure of TC5b during
mixed-solvent exposure encountered in iFNP processing. The simulations involve atomistic models of mixed solvents and
protein to capture the complexity of the hydrogen bonding and hydrophobic interactions between water, dimethylsulfoxide
(DMSO), and the protein. The combined analyses reveal structural unfolding of the protein in 11 M DMSO but confirm
complete refolding after release from the polymeric nanocarrier back into an aqueous phase.
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- Award ID(s):
- 1947720
- NSF-PAR ID:
- 10205659
- Date Published:
- Journal Name:
- ACS Nano
- ISSN:
- 1936-0851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acsnano.0c06056
