John M. Dyke

DFT studies of metal complexes relevant to ¹⁸ F PET tracers reveal that both the metal and precise chelator identities govern halide exchange, hydrolysis and stability, providing valuable insights for the design of new M– ¹⁸ F radiopharmaceuticals.

The thermodynamics and mechanisms of the atmospherically relevant reaction between dimethyl sulphide (DMS) and molecular chlorine (Cl₂) were investigated in the absence and presence of a single water molecule, using electronic structure methods.

Double ionization spectra of isothiocyanic acid (HNCS) have been measured using multi-electron and multi-ion coincidence techniques combined with high-level theoretical calculations. The adiabatic double ionization energy of HNCS is found at 27.1 ± 0.1 eV and is associated with the formation of the X 3A″ ground state of HNCS2+. The characteristics of different dissociation channels are examined and compared to the results of electronic structure calculations obtained by systematically elongating the three bonds H–NCS, HN–CS, and HNC–S. For instance, the adiabatic double ionization energy of the NCS fragment is deduced to be 30.95 ± 0.5 eV. In addition, the C+ and NS+ dissociation channels are of particular interest, possibly indicating the involvement of a structural rearrangement process upon doubly ionizing HNCS.

With the aim of obtaining improved molecular scaffolds for ¹⁸F binding to use in PET imaging, gallium(III) and iron(III) complexes with a macrocyclic bis-phosphinate chelator have been synthesized and their properties, including their fluoride binding ability, investigated. Reaction of Bn-tacn (1-benzyl-1,4,7-triazacyclononane) with paraformaldehyde and PhP(OR)₂ (R = Me or Et) in refluxing THF, followed by acid hydrolysis, yields the macrocyclic bis(phosphinic acid) derivative, H₂(Bn-NODP) (1-benzyl-4,7-phenylphosphinic acid-1,4,7-triazacyclononane), which is isolated as its protonated form, H₂(Bn-NODP)·2HCl·4H₂O, at low pH (HCl_aq), its disodium salt, Na₂(Bn-NODP)·5H₂O at pH 12 (NaOH_aq), or the neutral H₂(Bn-NODP) under mildly basic conditions (Et₃N). A crystal structure of H₂(Bn-NODP)·2HCl·H₂O confirmed the ligand's identity. The mononuclear [GaCl(Bn-NODP)] complex was prepared by treatment of either the HCl or sodium salt with Ga(NO₃)₃·9H₂O or GaCl₃, while treatment of H₂(Bn-NODP)·2HCl·4H₂O with FeCl₃ in aqueous HCl gives [FeCl(Bn-NODP)]. The addition of 1 mol. equiv of aqueous KF to these chloro complexes readily forms the [MF(Bn-NODP)] analogues. Spectroscopic analysis on these complexes confirms pentadentate coordination of the doubly deprotonated (bis-phosphinate) macrocycle via its N₃O₂ donor set, with the halide ligand completing a distorted octahedral geometry; this is further confirmed through a crystal structure analysis on [GaF(Bn-NODP)]·4H₂O. The complex adopts the geometric isomer in which the phosphinate arms are coordinated unsymmetrically (isomer 1) and with the stereochemistry of the three N atoms of the tacn ring in the RRS configuration, denoted (N)RRS, and the phosphinate groups in the RR stereochemistry, denoted (P)RR, (isomer 1/RR), together with its (N)SSR (P)SS enantiomer. The greater thermodynamic stability of isomer 1/RR over the other possible isomers is also indicated by density functional theory (DFT) calculations. Radiofluorination experiments on the [MCl(Bn-NODP)] complexes in partially aqueous MeCN/NaOAc_aq (Ga) or EtOH (Ga or Fe; i.e. without buffer) with ¹⁸F^- target water at 80 °C/10 min lead to high radiochemical incorporation (radiochemical yields 60-80% at 1 mg/mL, or ∼1.5 μM, concentration of the precursor). While the [Fe¹⁸F(n-NODP)] is unstable (loss of ¹⁸F^-) in both H₂O/EtOH and PBS/EtOH (PBS = phosphate buffered saline), the [Ga¹⁸F(Bn-NODP)] radioproduct shows excellent stability, RCP = 99% at t = 4 h (RCP = radiochemical purity) when formulated in 90%:10% H₂O/EtOH and ca. 95% RCP over 4 h when formulated in 90%:10% PBS/EtOH. This indicates that the new "Ga^III(Bn-NODP)" moiety is a considerably superior fluoride binding scaffold than the previously reported [Ga¹⁸F(Bn-NODA)] (Bn-NODA = 1-benzyl-4,7-dicarboxylate-1,4,7-triazacyclononane), which undergoes rapid and complete hydrolysis in PBS/EtOH (refer to Chem. Eur. J. 2015, 21, 4688-4694).

The figure shows the TS, formed from DMS·H₂O + Cl, that corresponds to the pathway with the largest rate coefficient in the presence of water.

The reaction of SiI₄ and PMe₃ in n-hexane produced the yellow salt, [SiI₃(PMe₃)₂]I, confirmed from its X-ray structure, containing a trigonal bipyramidal cation with trans-phosphines. This contrasts with the six-coordination found in (the known) trans-[SiX₄(PMe₃)₂] (X = Cl, Br) complexes. The diphosphines o-C₆H₄(PMe₂)₂ and Et₂P(CH₂)₂PEt₂ form six-coordinate cis-[SiI₄(diphosphine)], which were also characterized by X-ray crystallography, multinuclear NMR, and IR spectroscopy. Reaction of trans-[SiX₄(PMe₃)₂] (X = Cl, Br) with Na[BAr^F] (BAr^F = [B{3,5-(CF₃)₂C₆H₃}₄]) produced five-coordinate [SiX₃(PMe₃)₂][BAr^F], but while Me₃SiO₃SCF₃ also abstracted chloride from trans-[SiCl₄(PMe₃)₂], the reaction products were six-coordinate complexes [SiCl₃(PMe₃)₂(OTf)] and [SiCl₂(PMe₃)₂(OTf)₂] with the triflate coordinated. X-ray crystal structures were obtained for [SiCl₃(PMe₃)₂][BAr^F] and [SiCl₂(PMe₃)₂(OTf)₂]. The charge distribution across the silicon species was also examined by natural bond orbital (NBO) analyses of the computed density functional theory (DFT) wavefunctions. For the [SiX₄(PMe₃)₂] and [SiX₃(PMe₃)₂]⁺ complexes, the positive charge on Si decreases and the negative charge on X decreases going from X = F to X = I. Upon going from [SiX₄(PMe₃)₂] to [SiX₃(PMe₃)₂]⁺, i.e., removal of X^-, there is an increase in positive charge on Si and a decrease in negative charge on the X centers (except for the case X = F). The positive charge on P shows a slight decrease.

Single photon double and triple ionization of allene is investigated using multi-particle coincidence spectroscopies. Key findings comprise supporting evidence for a previously proposed roaming mechanism in H ₃ ⁺ formation by double ionization.

The results of the work of Tsona et al. are at variance with the earlier computational work performed by Chow et al. (PCCP 2016, 18, 30554–30569). Reasons for this are presented.