Rémi Maurice

Scrutinizing “Invisible” astatine: A challenge for modern density functionals

The main‐group 6p elements did not receive much attention in the development of recent density functionals. In many cases it is still difficult to choose among the modern ones a relevant functional for various applications. Here, we illustrate the case of astatine species (At, Zu2009=u200985) and we report the first, and quite complete, benchmark study on several properties concerning such species. Insights on geometries, transition energies and thermodynamic properties of a set of 19 astatine species, for which reference experimental or theoretical data has been reported, are obtained with relativistic (two‐component) density functional theory calculations. An extensive set of widely used functionals is employed. The hybrid meta‐generalized gradient approximation (meta‐GGA) PW6B95 functional is overall the best choice. It is worth noting that the range‐separated HSE06 functional as well as the old and very popular B3LYP and PBE0 hybrid‐GGAs appear to perform quite well too. Moreover, we found that astatine chemistry in solution can accurately be predicted using implicit solvent models, provided that specific parameters are used to build At cavities.

Advances on the Determination of the Astatine Pourbaix Diagram: Predomination of AtO(OH)2− over At− in Basic Conditions

It is generally assumed that astatide (At(-) ) is the predominant astatine species in basic aqueous media. This assumption is questioned in non-complexing and non-reductive aqueous solutions by means of high-pressure anion-exchange chromatography. Contrary to what is usually believed, astatide is found to be a minor species at pH=11. A different species, which also bears a single negative charge, becomes predominant when the pH is increased beyond 7. Using competition experiments, an equilibrium constant value of 10(-6.9) has been determined for the formation of this species from AtO(OH) with the exchange of one proton. The identification of this species, AtO(OH)2 (-) , is achieved through relativistic quantum mechanical calculations, which rule out the significant formation of the AtO2 (-) species, while leading to a hydrolysis constant of AtO(OH) in excellent agreement with experiment when the AtO(OH)2 (-) species is considered. Beyond the completion of the Pourbaix diagram of astatine, this new information is of interest for the development of (211) At radiolabeling protocols.

Effective bond orders from two-step spin–orbit coupling approaches: The I2, At2, IO+, and AtO+ case studies

The nature of chemical bonds in heavy main-group diatomics is discussed from the viewpoint of effective bond orders, which are computed from spin-orbit wave functions resulting from spin-orbit configuration interaction calculations. The reliability of the relativistic correlated wave functions obtained in such two-step spin-orbit coupling frameworks is assessed by benchmark studies of the spectroscopic constants with respect to either experimental data, or state-of-the-art fully relativistic correlated calculations. The I2, At2, IO(+), and AtO(+) species are considered, and differences and similarities between the astatine and iodine elements are highlighted. In particular, we demonstrate that spin-orbit coupling weakens the covalent character of the bond in At2 even more than electron correlation, making the consideration of spin-orbit coupling compulsory for discussing chemical bonding in heavy (6p) main group element systems.

211 At-labeled agents for alpha-immunotherapy: On the in vivo stability of astatine-agent bonds

The application of (211)At to targeted cancer therapy is currently hindered by the rapid deastatination that occurs inxa0vivo. As the deastatination mechanism is unknown, we tackled this issue from the viewpoint of the intrinsic properties of At-involving chemical bonds. An apparent correlation has been evidenced between inxa0vivo stability of (211)At-labeled compounds and the At-R (Rxa0=xa0C, B) bond enthalpies obtained from relativistic quantum mechanical calculations. Furthermore, we highlight important differences in the nature of the At-C and At-B bonds of interest, e.g. the opposite signs of the effective astatine charges, which implies different stabilities with respect to the biological medium. Beyond their practical use for rationalizing the labeling protocols used for (211)At, the proposed computational approach can readily be used to investigate bioactive molecules labeled with other heavy radionuclides.

Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates

Abstract211At is a most promising radionuclide for targeted alpha therapy. However, its limited availability and poorly known basic chemistry hamper its use. Based on the analogy with iodine, labelling is performed via astatobenzoate conjugates, but in vivo deastatination occurs, particularly when the conjugates are internalized in cells. Actually, the chemical or biological mechanism responsible for deastatination is unknown. In this work, we show that the C−At “organometalloid” bond can be cleaved by oxidative dehalogenation induced by oxidants such as permanganates, peroxides or hydroxyl radicals. Quantum mechanical calculations demonstrate that astatobenzoates are more sensitive to oxidation than iodobenzoates, and the oxidative deastatination rate is estimated to be about 6u2009×u2009106 faster at 37u2009°C than the oxidative deiodination one. Therefore, we attribute the “internal” deastatination mechanism to oxidative dehalogenation in biological compartments, in particular lysosomes.

The Heaviest Possible Ternary Trihalogen Species, IAtBr−, Evidenced in Aqueous Solution: An Experimental Performance Driven by Computations

Evidencing new chemical species in solution is particularly challenging when one works at ultra-trace concentrations, as is likely to happen with radioelements such as astatine (Z=85). Herein, quantum mechanical calculations were used to predict the narrow experimental domain in which it is possible to detect the presence of an exotic ternary trihalogen anion, IAtBr- , and thus to guide a series of experiments. By analyzing the outcomes of competition experiments, we show that IAtBr- exists and can even predominate in aqueous solution. The equilibrium constant associated with the reaction At+ +I- +Br- ⇌IAtBr- was determined to be 107.5±0.2 , which is in fair agreement with that predicted by density functional theory (106.9 ). This system not only constitutes the very first example of a ternary trihalogen species that involves the element astatine but is also the first trihalogen species reported to predominate in solution. Moreover, we show that the oxidation number of At is zero in this species, as in the other molecules and anions that At+ can form with Cl- , Br- , and I- ligands.

Experimental and computational evidence of halogen bonds involving astatine

The importance of halogen bonds—highly directional interactions between an electron-deficient σ-hole moiety in a halogenated compound and an acceptor such as a Lewis base—is being increasingly recognized in a wide variety of fields from biomedicinal chemistry to materials science. The heaviest halogens are known to form stronger halogen bonds, implying that if this trend continues down the periodic table, astatine should exhibit the highest halogen-bond donating ability. This may be mitigated, however, by the relativistic effects undergone by heavy elements, as illustrated by the metallic character of astatine. Here, the occurrence of halogen-bonding interactions involving astatine is experimentally evidenced. The complexation constants of astatine monoiodide with a series of organic ligands in cyclohexane solution were derived from distribution coefficient measurements and supported by relativistic quantum mechanical calculations. Taken together, the results show that astatine indeed behaves as a halogen-bond donor—a stronger one than iodine—owing to its much more electrophilic σ-hole.Halogen bonding is known to get stronger with increasing halogen polarizability, but some trends of the periodic table break down for heavy elements owing to relativistic effects. Now, through distribution coefficient measurements and relativistic quantum mechanical calculations, AtI has been shown to form stronger halogen bonds than I2—meaning that astatine conforms to the trend.

The bonding picture in hypervalent XF3 (X = Cl, Br, I, At) fluorides revisited with quantum chemical topology

Hypervalent XF3 (Xu2009=u2009Cl, Br, I, At) fluorides exhibit T‐shaped C2V equilibrium structures with the heavier of them, AtF3, also revealing an almost isoenergetic planar D3h structure. Factors explaining this behavior based on simple “chemical intuition” are currently missing. In this work, we combine non‐relativistic (ClF3), scalar‐relativistic and two‐component (Xu2009=u2009Bru2009−u2009At) density functional theory calculations, and bonding analyses based on the electron localization function and the quantum theory of atoms in molecules. Typical signatures of charge‐shift bonding have been identified at the bent T‐shaped structures of ClF3 and BrF3, while the bonds of the other structures exhibit a dominant ionic character. With the aim of explaining the D3h structure of AtF3, we extend the multipole expansion analysis to the framework of two‐component single‐reference calculations. This methodological advance enables us to rationalize the relative stability of the T‐shaped C2v and the planar D3h structures: the Coulomb repulsions between the two lone‐pairs of the central atom and between each lone‐pair and each fluorine ligand are found significantly larger at the D3h structures than at the C2v ones for Xu2009=u2009Clu2009−u2009I, but not with Xu2009=u2009At. This comes with the increasing stabilization, along the XF3 series, of the planar D3h structure with respect to the global T‐shaped C2v minima. Hence, we show that the careful use of principles that are at the heart of the valence shell electron pair repulsion model provides reasonable justifications for stable planar D3h structures in AX3E2 systems.

Unraveling the hydration-induced ground-state change of AtO+ by relativistic and multiconfigurational wave-function-based methods

The AtO+ cation is one of the main chemical forms that appear in the astatine Pourbaix diagram. This form can react with closed-shell species in solution, while in the gas phase, it has a spin-triplet ground spin-orbit-free (SOF) state. Spin-orbit coupling (SOC) mixes its MS = 0 component with the 1Σ+ singlet-spin component, while keeping an essentially-spin-triplet SOC ground-state. Therefore, it was suggested that AtO+ undergoes a hydration-induced ground-state change to explain its reactivity in solution with closed-shell species [J. Phys. Chem. B, 2013, 117, 5206-5211]. In this work, we track the nature of the low-lying SOF and SOC states when the hydration sphere of AtO+ is stepwise increased, using relativistic and multiconfigurational wave-function-based methods. This work clarifies previous studies by (i) giving additional arguments justifying a solvation-induced ground-state change in this system and (ii) clearly identifying for the first time the nature of the involved SOF and SOC many-electron states. Indeed, we find at the SOF level that AtO+ undergoes a ground-state reversal between 3Σ- and the closed-shell component of 1Δ, which leads to an essentially-spin-singlet and closed-shell SOC ground-state. This explains the observed reactivity of AtO+ with closed-shell species in solution.