Photochemical Reactions in the Synthesis of Protein–Drug Conjugates

The ability to modify biologically active molecules such as antibodies with drug molecules, fluorophores or radionuclides is crucial in drug discovery and target identification. Classic chemistry used for protein functionalisation relies almost exclusively on thermochemically mediated reactions. Our recent experiments have begun to explore the use of photochemistry to effect rapid and efficient protein functionalisation. This article introduces some of the principles and objectives of using photochemically activated reagents for protein ligation. The concept of simultaneous photoradiosynthesis of radiolabelled antibodies for use in molecular imaging is introduced as a working example. Notably, the goal of producing functionalised proteins in the absence of pre-association (non-covalent ligand-protein binding) introduces requirements that are distinct from the more regular use of photoactive groups in photoaffinity labelling. With this in mind, the chemistry of thirteen different classes of photoactivatable reagents that react through the formation of intermediate carbenes, electrophiles, dienes, or radicals, is assessed.     

Graph Theory Applied to Plasma Chemical Reaction Engineering

Plasma Chemistry and Plasma Processing - This work explores the following applications of graph theory to plasma chemical reaction engineering: assembly of a weighted directional graph with the key...     

A Districtwide Study of Automaticity When Included in Concept‐Based Elementary School Mathematics Instruction

While conceptual understanding of properties, operations, and the base‐ten number system is certainly associated with the ability to access math facts fluently, the role of math fact memorization to promote conceptual understanding remains contested. In order to gain insight into this question, this study looks at the results when one of three elementary schools in a school district implements mandatory automaticity drills for 10 minutes each day while the remaining two elementary schools, with the same curriculum and very similar demographics, do not. This study looks at (a) the impact that schoolwide implementation of automaticity drills has on schoolwide computational math skills as measured by the ITBS and (b) the relationship between automaticity and conceptual understanding as measured by statewide standardized testing. The results suggest that while there may be an association between automaticity and higher performance on standardized tests, caution should be taken before assuming there are benefits to promoting automaticity drills. These results are consistent with those that support a process‐driven approach to automaticity based on familiarity with properties and strategies associated with the base‐ten number system; they are not consistent with those that support an answer‐driven approach to automaticity based on memorization of answers.     

The die swell phenomenon

Summary A polymer melt or solution undergoes an increase in its cross-section when it is forced out of an orifice into air. The normal stress effects and elastic effects shown by these materials are frequently invoked to explain this die swell phenomenon. These explanations are here discussed and criticised. The analogous situation for a Newtonian jet is also discussed and the solution to a related problem of two-dimensional lowReynolds number flow is given.

---

Zusammenfassung Kunststoffschmelzen oder -lösungen zeigen nach dem Austritt aus einer Mündung in Luft eine Aufweitung des Querschnitts. Häufig wird dieses Schwell-Phänomen als Folge von Normalspannungen und Elastizität erklärt. Erklärungen dieser Art werden hier kritisch untersucht.Ebenso wird der entsprechende Fall einer Newtonschen Düsenströmung diskutiert. Für das verwandte Problem einer zweidimensionalen Strömung bei niedrigerReynolds-Zahl wird die Lösung gegeben.

     

Injection moulding of thermoplastics: Freezing of variable-viscosity fluids.

The injection moulding of thermoplastics involves, during mould filling, flows of hot polymer melts into mould networks, the walls of which are so cold that frozen layers form on them. An analytical study of such flows is presented here for the case when the Graetz and Nahme numbers are large and the Pearson number is small. Thus the flows are developing and temperature differences due to heat generation by viscous dissipation are sufficiently large to cause significant variations in viscosity (but the difference between the entry temperature of the polymer to a specific part of the mould network and the melting temperature of the polymer is not). Br Brinkman number - Gz Graetz number - h half-height of channel or disc - h ^* half-height of polymer melt region in channel or disc - L length of channel or pipe - m viscosity shear-rate exponent - Na Nahme number - p pressure - P pressure drop - Pe Péclet number - Pn Pearson number - Q volumetric flowrate - r radial coordinate in pipe or disc - R radius of pipe - Re Reynolds number - R _i inner radius of disc - R _o outer radius of disc - R ^* radius of polymer melt region in pipe - T temperature - T _ad adiabatic temperature rise - T _e entry polymer melt temperature - T _m melting temperature of polymer - T _max maximum temperature - T ₀ reference temperature - T _w wall temperature - flow-average temperature rise - u _r radial velocity in pipe or disc - u _x axial velocity in channel - u _y transverse velocity in channel or disc - u _z axial velocity in pipe - w width of channel - x axial coordinate in channel or modified radial coordinate in disc - y transverse coordinate in channel or disc - z axial coordinate in pipe - thermal conductivity of molten polymer - thermal conductivity of frozen polymer - scaled dimensionless axial coordinate in channel or pipe or radial coordinate in disc - ₀ undetermined integration constant - heat capacity of molten polymer - viscosity temperature exponent - dimensionless transverse coordinate in channel or disc - ^* dimensionless half-height of polymer melt region in channel or disc - H ^* scaled dimensionless half-height of polymer melt region in channel or disc or radius of polymer melt region in pipe - dimensionless temperature - ^* dimensionless wall temperature - scaled dimensionless temperature - numerical constant - µ viscosity of molten polymer - µ ₀ consistency of molten polymer - dimensionless pressure gradient - scaled dimensionless pressure gradient - density of molten polymer - dimensionless radial coordinate in pipe or disc - _i dimensionless inner radius of disc - ^* dimensionless radius of polymer melt region in pipe - dimensionless streamfunction - scaled dimensionless streamfunction - dummy variable - streamfunction - similarity variable - similarity variable     

Injection moulding of thermoplastics: Freezing of variable-viscosity fluids.

The injection moulding of thermoplastics involves, during mould filling, flows of hot polymer melts into mould networks, the walls of which are so cold that frozen layers form on them. An analytical study of such flows is presented here for the case when the Graetz number is small and the Nahme number is non-zero and can be large. Thus the flows are fully-developed and temperature differences due to heat generation by viscous dissipation are sufficiently large to cause significant variations in viscosity. Gz Graetz number - h half-height of channel or disc - h ^* half-height of polymer melt region in channel or disc - L length of channel or pipe - m viscosity shear-rate exponent - Na _Q Nahme number based on flowrate - Na _P Nahme number based on pressure drop - Na _PL lower critical value of Nahme number based on pressure drop - Na _PU upper critical value of Nahme number based on pressure drop - Na _P Nahme number based on pressure gradient - p pressure - P pressure drop - Q volumetric flowrate - r radial coordinate in pipe or disc - R radius of pipe - Re Reynolds number - R _i inner radius of disc - R ₀ outer radius of disc - R ^* radius of polymer melt region in pipe - T temperature - T _m melting temperature of polymer - T ₀ reference temperature - T _w wall temperature - u axial velocity in pipe or channel or radial velocity in disc - w width of channel - x axial coordinate in channel - y transverse coordinate in channel or disc - z axial coordinate in pipe - thermal conductivity of molten polymer - thermal conductivity of frozen polymer - heat capacity of molten polymer - viscosity temperature exponent - dimensionless transverse coordinate in channel or disc - ^* dimensionless half-height of polymer melt region in channel or disc - dimensionless temperature - ^* dimensionless wall temperature - µ viscosity of molten polymer - µ ₀ consistency of molten polymer - dimensionless pressure drop - dimensionless pressure gradient - density of molten polymer - dimensionless radial coordinate in pipe or disc - _i dimensionless inner radius of disc - ^* dimensionless radius of polymer melt region in pipe - dimensionless velocity     

Tuning Tetrazole Photochemistry for Protein Ligation and Molecular Imaging

Photochemistry provides a wide range of alternative reagents that hold potential for use in bimolecular functionalisation of proteins. Here, we report the synthesis and characterisation of metal ion binding chelates derivatised with disubstituted tetrazoles for the photoradiochemical labelling of monoclonal antibodies (mAbs). The photophysical properties of tetrazoles featuring extended aromatic systems and auxochromic substituents to tune excitation toward longer wavelengths (365 and 395 nm) were studied. Two photoactivatable chelates based on desferrioxamine B (DFO) and the aza-macrocycle NODAGA were functionalised with a tetrazole and developed for protein labelling with ⁸⁹Zr, ⁶⁴Cu and ⁶⁸Ga radionuclides. DFO-tetrazole ( 1 ) was assessed by direct conjugation to formulated trastuzumab and subsequent radiolabelling with ⁸⁹Zr. Radiochemical studies and cellular-based binding assays demonstrated that the radiotracer remained stable in vitro retained high immunoreactivity. Positron emission tomography (PET) imaging and biodistribution studies were used to measure the tumour specific uptake and pharmacokinetic profile in mice bearing SK-OV-3 xenografts. Experiments demonstrate that tetrazole-based photochemistry is a viable approach for the light-induced synthesis of PET radiotracers.