Perfluoro compounds as blood substitutes.

Inconceivable as it is, it has been proved that animals can survive after having had their blood massively or even totally replaced by emulsions of perfluorinated compounds in salines. “Bloodles” rats charged with an emulsion of perfluorotri-n-butylamine survived a five hour period in an atmosphere containing 50% oxygen and 50% carbon monoxide, i.e. in conditions where the transport of oxygen by the red cells is entirely blocked. This review discusses: (1) the experiments which have demonstrated the capability of blood substitutes based on perfluorinated compounds to sustain life; (2) the characteristics and preparation of the relevant perfluoro compounds and the production and handling of their emulsions; (3) their “physiology”, i.e. toxicity, life-span in the blood-stream, effect on the organs and their functions, and excretion properties. Obstacles remaining to be overcome in order to provide a safe blood substitute for medical practice include the availability of numerous series of well-defined pure and inert perfluorinated chemicals, the production of stable emulsions, the optimization of fluid balance, and the attainment of reasonable excretion rates. The accent is placed upon the role of the chemist in the progress of this research.     

ZINDO calculations of the ground state and electronic transitions in the tetracyanonickelate Ion,Ni(CN)(4)(2-)

ZINDO semiempirical calculations on the Ni(CN)(4)(2-) ion were performed, and ground-state energies for all 41 valence-orbital-based MOs and orbital transition components of the two lowest energy fully allowed electronic transitions are reported. Gaussian 94 was used to calculate ground-state energies as a comparison. The ground-state energies using ZINDO compare much more favorably with those found through ab initio techniques than with those from a reported INDO calculation. The found electronic transitions agree substantially with earlier assignments with the exception that several orbital transitions are required to adequately model the lowest energy allowed x,y-polarized experimental transition. Calculation parameters were optimized to give excellent agreement with experiment and may serve well for more complex arrangements of this ion.     

Chemical reactivity of analogous technetium(V) and rhenium(V) dioxo complexes

All complexes of the series [MO₂L₂]⁺ (M=Tc, Re; L=ethylenediamine (en), 1,3-diaminopropane (1,3-dap)) have been synthesized and their chemical reactivities investigated. The following properties were studied: stability of the aqueous solutions at different pH values, substitution kinetics, lipophilicity and protein binding. The complexes show very similar reactivity in aqueous solution. From a radiopharmaceutical point of view, no significant difference in their in vivo behavior is expected.     

Thermal denaturation of some proteins and its effect on their electrospray mass spectrat

The effects of beat on the electrospray mass spectra of eight globular proteins in solution were studied. These ranged from hardly noticeable to a dramatic shift in the mass spectrometric profile and a concomitant increase in ion abundance. This change is believed to be the result of thermal denaturation of the protein species in solution resulting in a transition from a more compact to a less compact conformation. We accounted for this transition by means of a recently proposed model based on aqueous solution acid/base equilibria. For cytochrome c, profiles calculated by means of this model agree well with experimental data. The ΔH of the denaturation reaction of cytochrome c in aqueous solution containing 0.2% acetic acid was calculated from experimental data to be 103.8 ± 9.2 kJ mol^?1, in good agreement with previous measurements.     

Rearrangement of 4-(1-haloalkyl)- and 4-(2-haloalkyl)-2-azetidinones into methyl omega-alkylaminopentenoates via transient aziridines and azetidines

The synthesis of 4-(1-haloalkyl)-2-azetidinones and 4-(2-haloalkyl)-2-azetidinones was investigated with use of the Staudinger reaction between in situ generated ketenes and alpha-haloimines or beta-haloimines. This new class of functionalized 2-azetidinones was further evaluated for its potential use as intermediates in the synthesis of highly functionalized compounds. The reaction of 4-(1-haloalkyl)-2-azetidinones and 4-(2-haloalkyl)-2-azetidinones with sodium methoxide in methanol yielded ring-opened products, i.e., methyl 2-alkoxy-4-(alkylamino)pentenoate and methyl 5-(alkylamino)pentenoate, respectively. Further attention was paid in detail to the reaction mechanism involved in this peculiar transformation. It was proven that these reactions proceeded via intermediate aziridines or azetidines.     

7-(2-Methoxycarbonylvinyl)-3-hydroxychromones: new dyes with red shifted dual emission

7-(2-Methoxycarbonylvinyl)-3-hydroxychromones have been synthesized using Heck coupling reaction from the corresponding 7-bromo-3-hydroxychromones. Introduction of the electron acceptor (2-methoxycarbonylvinyl) group at 7-position of 3-hydroxychromone results in a 30-40 nm red shift in absorption and >50 nm red shifts of both bands in emission. This derivatization allowed us to develop dyes with absorption maxima reaching 480 nm and dual emission in the red region of the spectrum. In comparison to the parent dyes, 7-acryl-3-hydroxychromones demonstrate significantly stronger solvatochromism. This is due to the acceptor group at 7-position, which increases the transfer character of the excited state of the dyes. The new dyes are highly prospective for the development of new fluorescent probes in biological research.     

First C-C bond formation in the Pauson-Khand reaction: Influence of carbon-carbon triple bond polarization on regiochemistry: A density functional theory study

The influence of carbon-carbon triple bond polarization on the regiochemistry of the Pauson-Khand reaction has been studied with the B3LYP functional. The regiochemistry determining step of this reaction, i.e., olefin insertion leading to cobaltacycle formation, has been examined with ethylene as the olefin and propyne, methyl 2-butynoate, and methyl propiolate as the acetylenes. From this study, it has been concluded that, in absence of overwhelming steric effects of an acetylene substituent, the regiochemistry is influenced by the polarization of the acetylenic bond, which arises from the different substituents. The initial C-C bond is preferentially formed with the acetylenic carbon that has the greater electron density: with propyne, this leads to a cyclopentenone having the methyl group in the α-position; with methyl 2-butynoate, to a cyclopentenone with the CO₂Me in the β-position; with methyl propiolate, which is virtually unpolarized in the complex, to a cyclopentenone with the CO₂Me in the α-position (a result of steric effects). These theoretical results are concordant with those observed experimentally with norbornene. The question of axial versus equatorial reactive positions for the coordinated olefin is also addressed and a kinetic simulation is presented.     

Tetrathiafulvalene crowns: redox-switchable ligands

A series of redox-responsive ligands that associate the electroactive tetrathiafulvalene core with polyether subunits of various lengths has been synthesized. X-ray structures are provided for each of the free ligands. The requisite structural criteria for reaching switchable ligands are satisfied for the largest macrocycles, that is, planarity of the 1,1',3,3'-tetrathiafulvalene (TTF) pi system and correctly oriented coordinating atoms. The ability of these ligands to recognize various metal cations as a function of the cavity size has been investigated by various techniques (LSIMS, 1H NMR, and UV/Vis spectroscopy, cyclic voltammetry). These systems exhibit an unprecedented high coordination ability among TTF crown ethers. Their switchable ligating properties have been confirmed by cyclic voltammetry, and metal-cation complexation has been illustrated by X-ray structures of three of the corresponding metal complexes (Pb2+, Sr2+, and Ba2+). Solid-state structures of these complexes display original packing modes with channel-like arrangements.     

Quantifying uncertainty with ensembles of surrogates for blackbox optimization

Blackbox optimization tackles problems where the functions are expensive to evaluate and where no analytical information is available. In this context, a tried and tested technique is to build surrogates of the objective and the constraints in order to conduct the optimization at a cheaper computational cost. This work introduces an extension to a specific type of surrogates: ensembles of surrogates, enabling them to quantify the uncertainty on the predictions they produce. The resulting extended ensembles of surrogates behave as stochastic models and allow the use of efficient Bayesian optimization tools. The method is incorporated in the search step of the mesh adaptive direct search (MADS) algorithm to improve the exploration of the search space. Computational experiments are conducted on seven analytical problems, two multi-disciplinary optimization problems and two simulation problems. The results show that the proposed approach solves expensive simulation-based problems at a greater precision and with a lower computational effort than stochastic models.