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Aim: To study safety, efficacy and weight loss with ADO09, a co‐formulation of insulin A21G and pramlintide, in type 1 diabetes. Materials and Methods: A randomized, two‐arm ambulatory 16‐week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment. Results: A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed. Conclusions: These results extend previous observations on the efficacy and safety of this insulin/pramlintide co‐formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia. [ABSTRACT FROM AUTHOR]

The cover image is based on the Article ADO09, a co-formulation of pramlintide and insulin A21G, lowers body weight versus insulin lispro in type 1 diabetes by Grit Andersen MD et al., https://doi.org/10.1111/dom.15827. [ABSTRACT FROM AUTHOR]

DFT calculations are reported of the energetics of C-H oxidative addition of benzene and fluorinated benzenes, ArFH (ArF = C6FnH5-n, n = 0-5) at ZrCp2 (Cp = η5-C5H5), TaCp2H, TaCp2CI, WCp2, ReCp(CO)2, ReCp(CO)(PH3), ReCp(PH3)2, RhCp(PH3), RhCp(CO), lrCp(PH3), lrCp(CO), Ni(H2PCH2CH2- PH2), Pt(H2PCH2CH2PH2). The change in M-C bond energy of the products fits a linear function of the number of fluorine substituents, with different coefficients corresponding to ortho-, meta-, and para-fluorine. The values of the ortho-coefficient range from 20 to 32 kJ mo-1, greatly exceeding the values for the meta- and para-coefficients (2.0-4.5 kJ mor-1). Similarly, the H-C bond energies of ArFH yield ortho- and para-coefficients of 10.4 and 3.4 kJ mol-1, respectively, and a negligible meta-coefficient. These results indicate a large increase in the M-C bond energy with ortho-fluorine substitution on the aryl ring. Plots of D(M-C) vs D(H-C) yield slopes RM-C/H-C that vary from 1.93 to 3.05 with metal fragment, all in excess of values of 1.1-1.3 reported with other hydrocarbyl groups. Replacement of PH3 by CO decreases RM-C/H-C significantly. For a given ligand set and metals in the same group of the periodic table, the value of RM-C/H-C does not increase with the strength of the M-C bond. Calculations of the charge on the aryl ring show that variations in ionicity of the M-C bonds correlate with variations in M-C bond energy. This strengthening of metal-aryl bonds accounts for numerous experimental results that indicate a preference for ortho-fluorine substituents. [ABSTRACT FROM AUTHOR]

Density functional theory has been used to calculate HC and MC bond dissociation enthalpies in order to evaluate the feasibility of correlating relative MC bond enthalpies ΔH(MC)rel with HC bond enthalpies ΔH(HC) via computational methods. This approach has been tested against two experimental correlations: a study of (a) Rh(H)(R)(Tp′)(CNCH2CMe3) [R = hydrocarbyl, Tp′ = HB(3,5-dimethylpyrazolyl)3] (Wick, D. D.; Jones, W. D. Organometallics 1999, 18, 495) and (b) Ti(R)(silox)2(NHSit-Bu3) (silox = OSit-Bu3) (Bennett, J. L.; Wolczanski, P. T. J. Am. Chem. Soc. 1997, 119, 10696). We show that the observation that MC bond enthalpies increase more rapidly with different substituents than HC bond enthalpies is reproduced by theory. Quantitative slopes of the correlation lines are reproduced within 4% of the experimental values with a B3PW91 functional and with very similar correlation coefficients. Absolute bond enthalpies are reproduced within 6% for HC bonds, and relative bond enthalpies for MC bonds are reproduced within 30 kJ mol-1 for RhC bonds and within 19 kJ mol-1 for TiC bonds. Values are also calculated with the BP86 functional. [ABSTRACT FROM AUTHOR]

Cp*2ZrH2 (1*) (Cp* = pentamethylcyclopentadienyl) reacts with perfluoropropene (2) to give Cp*2- ZrHF (3*) and hydrodefluorinated products under very mild conditions. Initial C-F bond activation occurs selectively at the vinylic terminal position of the olefin to exchange fluorine for hydrogen. Subsequent hydrodefluorination leads to the formation of the n-propylhydride complex Cp*2ZrH(CH2CH2CH3, which can be cleaved with dihydrogen to give propane and 1*. A theoretical study of the reaction of Cp2ZrH2 (Cp = cyclopentadienyl) and CF2=CF(CF3) has been undertaken. Several mechanisms have been examined in detail using DFT(B3PW91) calculations and are discussed for this H/F exchange: (a) internal olefin insertion/β-fluoride elimination, (b) external olefin insertion/β-fluoride elimination, and (c) F/H metathesis from either an inside or outside approach. Of these, the first case is found to be energetically preferred. Selective defluorination at the terminal carbon has been shown to be favored over defluorination at the substituted and allylic carbons. [ABSTRACT FROM AUTHOR]

Cp*(2)ZrH(2) (1) (Cp* = pentamethylcyclopentadienyl) reacts with perfluoropropene (2) to give Cp*(2)ZrHF (3) and hydrodefluorinated products under very mild conditions. Initial C-F bond activation occurs selectively at the vinylic terminal position of the olefin to exchange fluorine for hydrogen. Subsequent hydrodefluorination leads to the formation of the n-propylhydride complex Cp*(2)ZrH(CH(2)CH(2)CH(3)), which can be cleaved with dihydrogen to give propane and 1. A theoretical study of the reaction of Cp*(2)ZrH(2) (Cp* = cyclopentadienyl) and CF(2)[double bond]CF(CF(3)) has been undertaken. Several mechanisms have been examined in detail using DFT(B3PW91) calculations and are discussed for this H/F exchange: (a) internal olefin insertion/beta-fluoride elimination, (b) external olefin insertion/beta-fluoride elimination, and (c) F/H metathesis from either an inside or outside approach. Of these, the first case is found to be energetically preferred. Selective defluorination at the terminal carbon has been shown to be favored over defluorination at the substituted and allylic carbons.

Given the nucleophilicity of the [Pt(2)S(2)] ring, the evolution of [Pt(2)(mu-S)(2)(P intersection P)(2)] (P intersection P=1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp)) metalloligands in the presence of the simplest electrophilic species, the proton, has been studied. Combined use of experimental and theoretical data has allowed the whole set of reactions ensuing the protonation of the [Pt(2)S(2)] core to be established. The titration of [Pt(2)(mu-S)(2)(P intersection P)(2)] with HCl or HClO(4) was monitored mainly by (31)P[(1)H] NMR and mass techniques. Characterization of all the species involved was completed with the determination of the crystal structure of [Pt(SH)(2)(P intersection P)], for dppe and dppp, and [Pt(3)(mu(3)-S)(2)(dppp)(3)](PF(6))(2). The first protonation step of the [Pt(2)S(2)] core leads to the stable [Pt(2)(mu-S)(mu-SH)(P intersection P)(2)](+) complex, but the second step implies disintegration of the ring, thus giving rise to various mononuclear species. The subsequent evolution of some of these species allows regeneration of [Pt(2)(mu-S)(mu-SH)(P intersection P)(2)](+), evidencing the cyclic nature of this process. Whereas the reaction pathway is essentially common for both phosphine ligands, dppe and dppp, the different coordinating ability of Cl(-) or ClO(4) (-) determines the nature of the final products, [PtCl(2)(P intersection P)], [Pt(3)(mu(3)-S)(2)(P intersection P)(3)]Cl(2) or [Pt(3)(mu(3)-S)(2)(P intersection P)(3)](ClO(4))(2). DFT calculations have corroborated the thermodynamic feasibility of the reactions proposed on the basis of experimental data.