Relevance of Fluorinated Ligands to the Design of Metallodrugs for Their Potential Use in Cancer Treatment.

Fluorination of pharmaceutical agents has afforded crucial modifications to their pharmacological profiles, leading to important advances in medicinal chemistry. On the other hand, metallodrugs are considered to be valuable candidates in the treatment of several diseases, albeit with the caveat that they may exhibit pharmacological disadvantages, such as poor water solubility, low bioavailability and short circulating time. To surmount these limitations, two approaches have been developed: one based on the design of novel metallodrug-delivering carriers and the other based on optimizing the structure of the ligands bound to the metal center. In this context, fluorination of the ligands may bring beneficial changes (physicochemical and biological) that can help to elude the aforementioned drawbacks. Thus, in this review, we discuss the use of fluorinated ligands in the design of metallodrugs that may exhibit potential anticancer activity.

Bimetallic complexes that merge metallocene and pincer-metal building blocks: synthesis, stereochemistry and catalytic reactivity.

This perspective is to illustrate the synthesis and applications of bimetallic complexes by merging a metallocene and a (cyclopentadienyl/aryl) pincer metal complex. Four possible ways to merge metallocene and pincer-metal motifs are reported and representative examples are discussed in more detail. These bimetallic complexes have been employed in some important catalytic reactions such as cross-coupling, transfer hydrogenation or synthesis of ammonia. The metallocene fragment may tune the electronic properties of the pincer ligand, due to its redox reversible properties. Also, the presence of two metals in a single complex allows their electronic communication, which proved beneficial for, e.g., the catalytic activity of some species. The presence of the metallocene fragment provides an excellent opportunity to develop chiral catalysts, because the metallocene merger generally renders the two faces of the pincer-metal catalytic site diastereotopic. Besides, an extra chiral functionality may be added to the bimetallic species by using pincer motifs that are planar chiral, e.g. by using the different substituents of pincer ligand "arms" or non-symmetrical arene groupings. Post-functionalization of pre-formed pincer-metal complexes, via η6-coordination with an areneophile such as [CpRu]+ and [Cp*Ru]+ presents a striking strategy to obtain diastereomeric metallocene-pincer type derivatives, that actually involve half-sandwich metallocenes. This approach offers the possibility to create diastereomerically pure derivatives by using the chiral TRISPHAT anion. The authors hope that this report of the synthetic, physico-chemical properties and remarkable catalytic activities of metallocene-based pincer-metal complexes will inspire other researchers to continue exploring this realm.

Mechanochemistry: A Green Approach in the Preparation of Pharmaceutical Cocrystals.

Mechanochemistry is considered an alternative attractive greener approach to prepare diverse molecular compounds and has become an important synthetic tool in different fields (e.g., physics, chemistry, and material science) since is considered an ecofriendly procedure that can be carried out under solvent free conditions or in the presence of minimal quantities of solvent (catalytic amounts). Being able to substitute, in many cases, classical solution reactions often requiring significant amounts of solvents. These sustainable methods have had an enormous impact on a great variety of chemistry fields, including catalysis, organic synthesis, metal complexes formation, preparation of multicomponent pharmaceutical solid forms, etc. In this sense, we are interested in highlighting the advantages of mechanochemical methods on the obtaining of pharmaceutical cocrystals. Hence, in this review, we describe and discuss the relevance of mechanochemical procedures in the formation of multicomponent solid forms focusing on pharmaceutical cocrystals. Additionally, at the end of this paper, we collect a chronological survey of the most representative scientific papers reporting the mechanochemical synthesis of cocrystals.

A sensitive photoluminescent chemosensor for cyanide in water based on a zinc coordination polymer bearing ditert-butyl-bipyridine.

Sensitive and direct sensing of cyanide in buffered aqueous solutions at pH = 7.0 by three new blue photoluminescent zinc-1,4-cyclohexanedicarboxylato coordination polymers bearing di-alkyl-2,2'-bipyridines has been achieved. Specifically, a Zn-polymer with the general formula: {[Zn2(H2O)2(e,a-cis-1,4-chdc)2(4,4'-dtbb)2]·7H2O}n, (1,4-chdc = 1,4-cyclohexanedicarboxylato and 4,4'-dtbb = 4,4'-ditert-butyl-2,2'-bipyridine) has been synthesized in high yield and studied as a luminescent chemosensor for halides, pseudohalides and a series of oxyanions in neutral water. CN- ions can be quantitatively detected by this polymer based on complete quenching (λem = 434 nm) in the sub-micromolar concentration range with a pronounced selectivity over common anions such as acetate, bromide and iodide. The quenching response (KSV = 9.7(±0.2) × 104 M-1) by the addition of CN- was also observed in the presence of typical interfering anions with a very low detection limit of 0.9 µmol L-1 in buffered water at pH = 7.0. On the basis of the crystal structure and solid state CPMAS 13C-NMR correlation and 1H NMR, IR-ATR, MS-ESI(+) and SEM-EDS experiments, the optical change is attributed to the efficient release of its corresponding ditert-butyl-bipyridine, with the simultaneous formation of a zinc cyanide complex. The CPMAS 13C-NMR spectrum of the coordination polymer is consistent with the symmetry of the crystal structure. The use of flexible coordination polymers as fluorescent sensors for fast and selective detection of cyanide ions in pure aqueous solutions has been unexplored until now.

1,3-Bis[(naphthalen-2-ylsulfan-yl)meth-yl]benzene.

Mol-ecules of the title compound, C(28)H(22)S(2), are located on a crystallographic mirror plane with one half-mol-ecule in the asymmetric unit. The dihedral angle between the phenyl ring and the naphthyl unit is 83.14 (7)°. In the crystal, mol-ecules are inter-connected by C-H⋯S and C-H⋯π inter-actions.

(E)-2-{[2-(2-Hy-droxy-ethyl-amino)-ethyl-imino]-meth-yl}phenol.

The asymmetric unit of the title compound, C(11)H(16)N(2)O(2), contains two independent conformational isomers which show intra-molecular aromatic-imine O-H⋯N hydrogen bonds. In the crystal, neighboring mol-ecules are linked through inter-molecular aliphatic-aliphatic O-H⋯N, aliphatic-aromatic N-H⋯O and C-H⋯O inter-actions into hydrogen-bonded layers parallel to the ab plane.