ESI-MS and thermal melting studies of nanoscale platinum(ii) metallomacrocycles with DNA

The hydrophilic, long-chain diamine PEGda (O,O′-bis(2-aminoethyl)octadeca(ethylene glycol)), when complexed with cis-protected Pt(II) ions afforded water-soluble complexes of the type [Pt(N,N)(PEGda)](NO3)2 (N,N = N,N,N′,N′-tetramethyl-1,2-diaminoethane (tmeda), 1,2-diaminoethane (en), and 2,2′-bipyridine (2,2′-bipy)) featuring unusual 62-membered chelate rings. Equimolar mixtures containing either the 16-mer duplex DNA D2 or the single-stranded D2a and [Pt(N,N)(PEGda)]2+ were analyzed by negative-ion ESI-MS. Analysis of D2-Pt(II) mixtures showed the formation of 1:1 adducts of [Pt(en)(PEGda)]2+, [Pt(tmeda)(PEGda)]2+ and the previously-described metallomacrocycle [Pt2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+ with D2; the dinuclear species bound to D2 most strongly, consistent with its greater charge and aromatic surface area. D2 formed 1:2 complexes with the acyclic species [Pt(2,2′-bipy)(Mebipy)2]4+ and [Pt(2,2′-bipy)(NH3)2]2+. Analyses of D2a-Pt(II) mixtures gave results similar to those obtained with D2, although fragmentation was more pronounced, indicating that the nucleobases in D2a play more significant roles in mediating the decomposition of complexes than those in D2, in which they are paired in a complementary manner. Investigations were also conducted into the effects of selected platinum(II) complexes on the thermal denaturation of calf thymus DNA (CT-DNA) in buffered solution. Both [Pt2(2,2′-bipy)2{4,4′-bipy(CH2)64,4′-bipy}2]8+ and [Pt(2,2′-bipy)(Mebipy)2]4+ stabilized CT-DNA. In contrast, [Pt(tmeda)(PEGda)]2+ and [Pt(en)(PEGda)]2+ (as well as free PEGda) caused negligible changes in melting temperature (ΔTm), suggesting that these species interact weakly with CT-DNA

[1,2-Bis(diphenyl­phosphino)-1,2-dicarba-closo-dodeca­borane-κ2 P,P′][7,8-bis­(di­phenyl­phosphino)-7,8-dicarba-nido-undeca­borato-κ2 P,P′]gold(I)–dichloro­methane–water (2/1/1)

The title compound, [Au(C26H30B10P2)(C26H30B9P2)]·0.5CH2Cl2·0.5H2O, contains two independent complex mol­ecules in the asymmetric unit. The gold(I) centres display a distorted tetra­hedral geometry. The complex is stablized through weak intra­molecular π–π stacking (Cg⋯Cg = 4.17 Å) and edge-to-face inter­actions (H⋯Cg = 3.21 Å). Adjacent mol­ecules inter­act through C—H⋯π (H⋯Cg = 2.88 Å) and B—H⋯π (H⋯Cg = 3.15 Å) contacts, forming a three-dimensional network, with solvent mol­ecules occupying the cavities. One of the phenyl groups was disordered over two sites with occupancy factors of 0.65 and 0.35

Nonclassical Phenyl Bioisosteres as Effective Replacements in a Series of Novel Open-Source Antimalarials

The replacement of one chemical motif with another that is broadly similar is a common method in medicinal chemistry to modulate the physical and biological properties of a molecule (i.e., bioisosterism). In recent years, bioisosteres such as cubane and bicyclo[1.1.1]pentane (BCP) have been used as highly effective phenyl mimics. Herein, we show the successful incorporation of a range of phenyl bioisosteres during the open-source optimization of an antimalarial series. Cubane () and -carborane () analogues exhibited improved potency against compared to the parent phenyl compound; however, these changes resulted in a reduction in metabolic stability; unusually, enzyme-mediated oxidation was found to take place on the cubane core. A BCP analogue () was found to be equipotent to its parent phenyl compound and showed significantly improved metabolic properties. While these results demonstrate the utility of these atypical bioisosteres when used in a medicinal chemistry program, the search to find a suitable bioisostere may well require the preparation of many candidates, in our case, 32 compounds

Platinum(II) and palladium(II) metallomacrocycles derived from cationic 4,4 '-bipyridinium, 3-aminopyrazinium and 2-aminopyrimidinium ligands

A series of cationic, ditopic N-donor ligands based on 4,4-bipyridine (4,4-bipy), 3-aminopyrazine (apyz) and 2-aminopyrimidine (apym), each incorporating two positively-charged N-heterocycles linked by a conformationally-flexible spacer unit, have been synthesised and treated with palladium(II) or platinum(II) precursors [M(2,2-bipy)(NO3)2] (M = Pd(II) or Pt(II)) to form highly cationic metallocyclic species. Treatment of 1,6-bis(4,4-bipyridinium)hexane nitrate with [M(2,2-bipy)(NO3)2] in aqueous solution, followed by the addition of KPF6, resulted in the formation of the [2+2] species [M2(2,2-bipy)2{4,4-bipy(CH2)64,4-bipy}2](PF6)8. Treatment of [Pd(PhCN)2Cl2] with 1,3-bis(4,4-bipyridinium)propane hexafluorophosphate in MeCN afforded [Pd2Cl4{4,4-bipy(CH2)34,4-bipy}2](PF6)4. When the cationic apyz or apym ligands were used in aqueous solution, the analogous metallomacrocycles did not form. Instead, deprotonation of the exocyclic amino group occurred upon coordination of the ligand to afford a tetranuclear [4+2] species in the case of platinum(II), with Pt(II)Pt(II) bonding supported by strong UV-vis absorption at = 428 nm which was assigned to a metal-metal-to-ligand charge transfer (MMLCT) band. Thus, treatment of 1,6-bis(3-aminopyrazinium)hexane nitrate with [Pt(2,2-bipy)(NO3)2], followed by the addition of KPF6, led to the formation of the red species [Pt4(2,2-bipy)4{apyz(CH2)6apyz–2H}2](PF6)8. No related products could be identified with palladium(II), consistent with the low propensity for this metal ion to form strong Pd(II)Pd(II) bonding interaction

Dicarba-closo-dodecaborane(12) derivatives of phosphonium salts: easy formation of nido-carborane phosphonium zwitterions

The first examples of arylphosphonium salts containing a dicarba-closo-dodecaborane(12) (closo-carborane) are reported; in contrast to the 1,12-carborane derivative, the 1,2- and 1,7-isomers undergo a facile deboronation reaction in polar solvents to afford the corresponding nido-carborane phosphonium zwitterions

Element 5 – Boron

2019 is the International Year of the Periodic Table of Chemical Elements (IYPT 2019), as declared by the United Nations General Assembly. This invited paper on boron is one in a series of essays about the chemical elements

Molecular Recognition of an Adenine Derivative by Organoplatinum(II) Complexes with Hydrogen-Bonding Functionality

The first examples of adenine binding by isomeric organoplatinum(II) complexes bearing H-bonding nicotinic and isonicotinic acid ligands are reported. Notably, a subtle switching of the H-bonding functionality from the 3- to 4-position of the pyridyl ring leads to a significant change in both the strength of association and the site of adenine binding.Australian Research Council (ARC