Structural studies of Perfluoroaryldiselenadiazolyl Radicals: Insights into Dithiadiazolyl Chemistry

Synopsis Diselenadiazolyls exhibit a stronger tendency to dimerize in the solid state than their corresponding dithiadiazolyl (DTDA) radicals, reflected in a range of dimerization modes for (p-XC6F4CNSeSeN)2, which contrast with those of the monomeric DTDA radicals, p-XC6F4CNSSN. The structure of (p-NCC6F4CNSeSeN)2 reflects a buildup of molecular strain in order to accommodate both dimerization and structure-directing CN···Se contacts, whereas the suppression of dimerization releases molecular strain yet retains structure-directing CN···S contacts for the corresponding DTDA radical

A [HN(BH═NH)2]2– Dianion, Isoelectronic with a β-Diketiminate

Producción CientíficaThe 1:2 reaction of the Al(III) β-diketiminate dihydride [{DMPnacnac}AlH2] (DMPnacnac = HC{C(Me)N(2,6-Me2-C6H3)}2) (1) with ammonia–borane (NH3BH3) gives the new complex [{DMPnacnac}Al{NHBH)2NH}] (3), whose [HN(BHNH)2]2– dianion is isoelectronic with β-diketiminate anions.2019-03-15Ministerio de Economía, Industria y Competitividad - Agencia Estatal de Investigación (AEI)European Research Council (ERC) and the European Social Fund (ESF)European Social Fund (ESF)Ramón y Cajal contract (RG-R, RYC-2015–19035

A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors

<p>Abstract</p> <p>Background</p> <p>Doxorubicin is a common anticancer agent used in the treatment of a number of neoplasms, with the lifetime dose limited due to the potential for cardiotoxocity. This has motivated efforts to develop optimal dosage regimes that maximize anti-tumor activity while minimizing cardiac toxicity, which is correlated with peak plasma concentration. Doxorubicin is characterized by poor penetration from tumoral vessels into the tumor mass, due to the highly irregular tumor vasculature. I model the delivery of a soluble drug from the vasculature to a solid tumor using a tumor cord model and examine the penetration of doxorubicin under different dosage regimes and tumor microenvironments.</p> <p>Methods</p> <p>A coupled ODE-PDE model is employed where drug is transported from the vasculature into a tumor cord domain according to the principle of solute transport. Within the tumor cord, extracellular drug diffuses and saturable pharmacokinetics govern uptake and efflux by cancer cells. Cancer cell death is also determined as a function of peak intracellular drug concentration.</p> <p>Results</p> <p>The model predicts that transport to the tumor cord from the vasculature is dominated by diffusive transport of free drug during the initial plasma drug distribution phase. I characterize the effect of all parameters describing the tumor microenvironment on drug delivery, and large intercapillary distance is predicted to be a major barrier to drug delivery. Comparing continuous drug infusion with bolus injection shows that the optimum infusion time depends upon the drug dose, with bolus injection best for low-dose therapy but short infusions better for high doses. Simulations of multiple treatments suggest that additional treatments have similar efficacy in terms of cell mortality, but drug penetration is limited. Moreover, fractionating a single large dose into several smaller doses slightly improves anti-tumor efficacy.</p> <p>Conclusion</p> <p>Drug infusion time has a significant effect on the spatial profile of cell mortality within tumor cord systems. Therefore, extending infusion times (up to 2 hours) and fractionating large doses are two strategies that may preserve or increase anti-tumor activity and reduce cardiotoxicity by decreasing peak plasma concentration. However, even under optimal conditions, doxorubicin may have limited delivery into advanced solid tumors.</p

Catalytic versus stoichiometric dehydrocoupling using main group metals

A primary factor influencing catalyticversus stoichiometric behaviour of molecular main group species in homogeneous dehydrocoupling reactions is the redox stability of the metal centre. Thus, only in the case of redox-stable metals has catalytic behaviour so far been observed, through genuinely hydrogenic coupling (E–H + E′–H → E–E′ + H2), whereas for redox-unstable metals oxidative dehydrocoupling is seen (E–H + E′–H → E–E′ + 2H+ + 2e). The mechanisms of catalytic P–H/P–H and B–H/N–H dehydrocoupling involving main group systems are closely related to d0 transition metal counterparts and produce a similar range of products, although the main group systems reported so far are not as active as the most active transition metal catalysts

An investigation of halogen bonding as a structure-directing interaction in dithiadiazolyl radicals

Published as part of a Crystal Growth and Design virtual special issue on Crystalline Molecular Materials: From Structure to Function.The preparation and characterization of the halo-functionalized dithiadiazolyl radicals p-XC6F4CNSSN (X = Br (1) or I (2)) are described. Compound 1 is trimorphic. The previously reported phase 1α (Z′ = 1) comprises monomeric radicals, whereas 1β comprises a mixture of one cis-oid π*−π* dimer and one monomer (Z′ = 3), and 1γ exhibits a single cis-oid dimer (Z′ = 2) in the asymmetric unit. We have only been able to isolate a single polymorph of 2, isomorphous with 1α. Both the bromo and iodo groups in 1 and 2 promote sigma-hole type interactions of the type C–X···N (X = Br, I), reflecting the increasing strength of this interaction for the heavier halo-derivatives. An analysis of the intermolecular forces is made using dispersion corrected density functional theory (DFT) (UM06-2X-D3/LACV3P*) and compared to a unified pair potential model (UNI) embodied in the crystallographic software Mercury. While there is a correlation between DFT and UNI force-field models, there are some discrepancies, although both reveal that a number of intermolecular contacts beyond the sum of the van der Waals radii are significant (>5 kJ mol–1). A natural bond order analysis of the intermolecular interactions reveals lone pair donation from the heterocyclic N atom to C–X or S–S σ* orbitals contributes to these intermolecular interactions with relative energies in the order C–I > SN-II > C–Br > SN-III. The magnetism of 2 reveals a broad maximum in χ around 20 K indicative of short-range antiferromagnetic interactions. These are supported by DFT calculations that reveal a set of three significant exchange interactions which propagate in two dimensions.We would like to acknowledge the NSERC DG program for financial support (J.M.R.) and C.F.I./O.R.F. for an infrastructure grant. M.A.N. would like to thank the NSERC for a CGS-M scholarship. J.C. acknowledges support from Grant PGC-2018−099024-B100. Additional support from Diputacion General de Aragon (DGA-M4) is also acknowledged. J.C and A.A. would like to acknowledge the use of Servicio General de Apoyo a la Investigacion-SAI, Universidad de Zaragoza.Peer reviewe