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A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus afford kinetic control over the drug de-threading and release.

The interaction of salphen-type NiII, CuII and ZnII complexes with native DNA was investigated by exploiting linear dichroism experiments. The NiII complex behaves as a typical intercalator, binding strongly and stiffening and unwinding the DNA. The strength of the DNA interaction is slightly weaker for the copper complex and much weaker for the zinc complex. Plasmid-DNA gel electrophoresis experiments indicated that while CuII and ZnII complexes do not induce the unwinding of supercoiled DNA, the NiII complex has a nuclease activity without the addition of external agents. On the other hand, as shown in the PCR assays, we demonstrate that, at the used concentrations, only the CuII complex is able to inhibit the DNA amplification mediated by Taq DNA polymerase. In this paper we have also reported a detailed characterization of the three compounds including 2D-NMR and ESI-mass experiments and X-ray single crystal structure of the copper and nickel compounds.

The conjugation of arginine residues at the ends of a metallo-supramolecular triple-helical cylinder enables absolute control over the helicity of the cylinder core, and boosts the DNA junction recognition by the complexes and their activity against a cancer cell line., (This journal is © The Royal Society of Chemistry 2011)

Previously a range of androgen conjugates with non-conventional platinum(II) complexes have been synthesised with the aim of enhancing cellular delivery, and which have shown increased cytotoxic activity compared with non-steroidal compounds (M. J. Hannon et al., Dalton Trans., 2010, DOI: 10.1039/c0dt00838a). To further study this, the complexes have been assessed for their ability to bind to and alter the structure of DNA. All platinum(II) complexes studied herein bind to model nucleo-bases and DNA, but to our surprise, testosterone-based complexes caused the DNA helix to undergo significant unwinding and bending, whereas non-steroidal control complexes caused minimal structural alterations. These effects are similar to those cisplatin induces on DNA structure despite the fact that these compounds produce a monofunctional lesion. This ability attributed to interactions between the DNA helix and bulky steroidal skeleton of testosterone, coupled with the enhanced cellular delivery induced by the steroid make the steroid approach an exciting way to explore non-conventional platinum drug delivery.

Investigating the methods commonly used to evaluate in vitro cytotoxicity of novel compounds, specifically non-covalent DNA binders, identifies that these methods may not be appropriate. The level of anticancer activity depends not only on the incubation time but also on the absolute amount (number of moles) of drug compound applied, rather than the concentration.

Triple helical di-iron complexes, readily prepared through interaction of iron(II) ions with imine-based ligands, are cylinder-shaped tetracations comparable in size and shape to common protein DNA recognition units. They have a strong tendency to coil DNA, and have recently been found to induce formation of three-way junctions in palindromic oligonucleotides. To introduce potential H bond acceptor units onto the surface of triple-helicates, new iron(II) complexes have been synthesized in which the central linking unit in the bridging ligand is S or O, instead of CH(2). The DNA binding properties of these new metallo-helicates were studied using UV-vis spectroscopy and circular and linear dichroism. Results show that the three iron triple helicates bind the DNA in a similar way but that the stability of the triple helicate unit is decreased with the O linked bridging ligand.

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L(1)L(2)]((2-n)+), and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}(2){mu-H(2)N(CH(2))(6)NH(2)}](4+). The ligand tpy is 2,2':6',2''-terpyridine and the ligand L(1) is a bidentate ligand, namely, apy (2,2'-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L(2) is a labile monodentate ligand, being Cl(-), H(2)O, or CH(3)CN. All six species containing a labile L(2) were found to be able to coordinate to the DNA model base 9-ethylguanine by (1)H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure-activity relationships that might be used to guide optimization of the activity of agents of this class of compounds.

The supramolecular iron cylinder, [Fe(2)L(3)]Cl(4) (L = C(25)H(20)N(4)), shows unprecedented DNA binding in vitro, inducing intramolecular DNA coiling and also targeting Y-shaped DNA junctions. We investigated its effects on proliferation and survival in both tumor and normal cell lines. Iron cylinder reduced mitochondrial activity of cultures with potency similar to cisplatin, inhibited the cell cycle, and increased cell death by apoptosis. Associated with this, we observed a lowering of the association of propidium iodide with cellular DNA consistent with an observed competitive displacement of PI from naked DNA by cylinders. Importantly, and in contrast to existing anticancer drugs such as cisplatin, the iron cylinder [Fe(2)L(3)](4+) was not genotoxic. In summary, the design of metal complexes such as [Fe(2)L(3)](4+) with potential anticancer properties in the absence of genotoxicity may represent a significant step toward therapeutic advancement.

The interaction of enantiomerically pure dinuclear complexes of the form [Ru2(L-L)4L1]4+ (where L-L = 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen) and L1 = bis(pyridylimine) ligand ((C5H4N)CN(C6H4))2CH2)) with ct-DNA have been investigated by absorbance, circular dichroism, fluorescence displacement assays, thermal analysis, linear dichroism and gel electrophoresis. The complexes all bind more strongly to DNA than ethidium bromide, stabilise DNA and have a significant bending effect on DNA. The data for Delta,Delta-[Ru2(bpy)4L1]4+ are consistent with it binding to DNA outside the grooves wrapping the DNA about it. By way of contrast the other complexes are groove-binders. The phen complexes provide a chemically and enantiomerically stable alternative to the DNA-coiling di-iron triple-helical cylinder previously studied. In contrast to the di-iron helicates, the phen complexes show DNA sequence effects with Delta,Delta-[Ru2(phen)4L1]4+ binding preferentially to GC and Lambda,Lambda-[Ru2(phen)4L1]4+ to AT.

Two novel copper(ii) terpyridine complexes, [Cu(atpy)(NO(3))(H(2)O)](NO(3)).3H(2)O () and [Cu(ttpy)(NO(3))(2)] () (atpy = 4'-p-N9-adeninylmethylphenyl-2,2':6,2''-terpyridine; ttpy = 4'-p-tolyl-2,2':6,2''-terpyridine) have been prepared and structurally characterized by X-ray crystallography. Both complexes show a CuN(3)O(2) coordination in a square pyramidal (4 + 1) geometry with terpyridine acting as an equatorial ligand. For complex , intermolecular AA base pairing interaction is observed between N(6) and N(1) of adjacent adenines with N(6)N(1) of 3.027(7) A. A molecular dynamics simulation of the DNA binding of two complexes showed that the adenine moiety plays an important role in the intercalation of into DNA. This is verified by UV, fluorescence, circular dichroism and flow linear dichroism studies. The promotional effect from the adenine moiety to the intracellular DNA binding of complex is also confirmed by the inductively coupled plasma mass (ICP-MS) spectrometry data which showed a significant higher copper content in DNA isolated from complex treated MCF-7 and HeLa cells.

[Fe(2)L(3)](4+) (L = C(25)H(20)N(4)) is a synthetic tetracationic supramolecular cylinder (with a triple helical architecture) that targets the major groove of DNA and can bind to DNA Y-shaped junctions. To explore the DNA-binding mode of [Fe(2)L(3)](4+), we examine herein the interactions of pure enantiomers of this cylinder with DNA by biochemical and molecular biology methods. The results have revealed that, in addition to the previously reported bending of DNA, the enantiomers extensively unwind DNA, with the M enantiomer being the more efficient at unwinding, and exhibit preferential binding to regular alternating purine-pyrimidine sequences, with the M enantiomer showing a greater preference. Also, interestingly, the DNA binding of bulky cylinders [Fe(2)(L-CF(3))(3)](4+) and [Fe(2)(L-Ph)(3)](4+) results in no DNA unwinding and also no sequence preference of their DNA binding was observed. The observation of sequence-preference in the binding of these supramolecular cylinders suggests that a concept based on the use of metallosupramolecular cylinders might result in molecular designs that recognize the genetic code in a sequence-dependent manner with a potential ability to affect the processing of the genetic code.

Metallosupramolecular chemistry was used to design a new class of synthetic agents, namely, tetracationic supramolecular cylinders, that bind strongly and noncovalently in the major groove of DNA. To gain additional information on interactions of the cylinders with DNA we explored DNA unwinding and sequence-specific binding properties, as well as DNA photonuclease activity of ruthenium(II) metallosupramolecular cylinder [Ru(2)L(3)](4+), where L is a bis-pyridylimine ligand. We found that [Ru(2)L(3)](4+) unwinds negatively supercoiled plasmid DNA and exhibits binding preference to regular alternating purine-pyrimidine sequences in a similar way to the [Fe(2)L(3)](4+) analogue. Photocleavage studies showed that, unlike [Fe(2)L(3)](4+), [Ru(2)L(3)](4+) induces single-strand breaks on irradiation by visible and UVA light and cleaves DNA mainly at guanine residues contained preferentially in regularly alternating purine-pyrimidine nucleotides. As [Ru(2)L(3)](4+) binds and cleaves DNA in a sequence-dependent manner, it may provide a useful tool for basic and applied biology, such as for controlled manipulation of the genome.

In order to probe the DNA-helicate interactions responsible for the DNA binding and remarkable changes of the DNA secondary structure induced by a tetracationic bi-metallo helicate [Fe(2)(L(1))(3)](4+) (L(1)=C(25)H(20)N(4)), we have designed and synthesised derivatives with hydrophobic methyl groups at different positions on the ligand backbone. Two dimetallo helicates [Fe(2)(L(i))(3)](4+) were prepared using ligands L(3) and L(5) with the methyl substituent on, respectively, the 3 and 5 positions of the pyridyl ring thus producing a wider or slightly longer tetracationic DNA binder. UV/visible absorbance, circular and linear dichroism spectroscopies have been used to characterize the interactions of the cylinders with DNA with the aim of investigating any sequence preference or selectivity upon binding. Competitive binding studies using fluorescent dyes Hoechst 33258 (a minor groove binder), ethidium bromide (an intercalator) and a major groove binding cation (cobalt (III) hexammine) which induces the B-->Z transition have been employed to determine the binding geometries of the enantiomers of two methylated helicates (L(3) and L(5)) to DNA and compare with the data obtained previously for the unmethylated analogue (L(1)). The results demonstrate that the racemic mixtures and the resolved enantiomers of all helicates bind to DNA inducing structural changes. The overall conclusion from the effect of adding these groups to the surface of the parent helicate is that increasing the width (L(3)) reduces the DNA binding strength, the bending and coiling effect and the groove selectivity of the enantiomers compared with the parent compound. There is limited evidence to suggest a slight GC sequence preference. Lengthening the helicate (L(5)) results in DNA interactions similar to those of the parent compounds, with an increased preference of the P enantiomer for the minor groove indicating an enhancement of mode selectivity.

A tetracationic supramolecular helicate, [Fe2L3]4+ (L = C25H20N4), with a triple-helical architecture is found to induce the formation of a three-way junction (3WJ) of deoxyribonucleotides with the helicate located in the center of the junction. NMR spectroscopic studies of the interaction between the M enantiomer of the helicate and two different oligonucleotides, [5'-d(TATGGTACCATA)]2 and [5'-d(CGTACG)]2, show that, in each case, the 2-fold symmetry of the helicate is lifted, while the 3-fold symmetry around the helicate axis is retained. The 1:3 helicate/DNA stoichiometry estimated from 1D NMR spectra supports a molecular model of a three-way junction composed of three strands. Three separate double-helical arms of the three-way junction are chemically identical giving rise to one set of proton resonances. The NOE contacts between the helicate and DNA unambiguously show that the helicate is fitted into the center of the three-way junction experiencing a hydrophobic 3-fold symmetric environment. Close stacking interactions between the ligand phenyl groups and the nucleotide bases are demonstrated through unusually large downfield shifts (1-2 ppm) of the phenyl protons. The unprecedented 3WJ arrangement observed in solution has also been found to exist in the crystal structure of the helicate adduct of [d(CGTACG)2] (Angew. Chem., Int. Ed. 2006, 45, 1227).

In this work we present the results of a molecular simulation study of two different tetracationic bis iron(II) supramolecular cylinders interacting with DNA. One cylinder has been shown to bind in the major groove of DNA and to induce dramatic coiling of the DNA; the second is a derivative of the first, with additional methyl groups attached so as to give a larger cylinder-radius. The simulations show that both cylinders bind strongly to the major groove of the DNA, and induce complex structural changes in A-T rich regions. Whereas the parent cylinder tends to bind along the major groove, the derivatised cylinder tends to twist so that only one end remains within the major groove. Both G-C rich and A-T rich binding sites for the derivatised cylinder are discussed.

Non-covalent DNA-recognition by synthetic agents is surveyed in this tutorial review, and contrasted with biomolecular DNA-recognition. The principles and forces involved in DNA recognition are similar to those seen elsewhere in the wider field of supramolecular chemistry, although the size, surface dimensions and nature of DNA introduce new possibilities and challenges. Recent discoveries of new binding motifs, and new biological structural and genomic information from bioscience, are affording new opportunities for supramolecular chemistry, where shape, fit and orientation play such an important role.

The interaction of metallosupramolecular cylinders with DNA three-way junctions has been studied by gel electrophoresis. A recent X-ray crystal structure of a palindromic oligonucleotide forming part of a complex with such a cylinder revealed binding at the heart of a three-way junction structure. The studies reported herein confirm that this is not solely an artefact of crystallisation and reveal that this is a potentially very powerful new mode of DNA recognition with wide scope. The cylinders are much more effective at stabilizing three-way junctions than simple magnesium di-cations or organic or metallo-organic tetra-cations, with the M cylinder enantiomer being more effective than P. The recognition is not restricted to three-way junctions formed from palindromic DNA with a central AT step at the junction; non-palindromic three-way junctions and those with GC steps are also stabilised. The cylinder is also revealed to stabilise other Y-shaped junctions, such as that formed at a fraying point in duplex DNA (for example, a replication fork), and other DNA three-way junction structures, such as those containing unpaired nucleotides, perhaps by opening up this structure to access the central cavity.

A set of cyclic tetranuclear complexes of the metallacalix[4]arene type with formula [{Pt(en)(L)}(4)](4+) (en=ethylenediamine; 2: LH=5-chloro-2-hydroxypyrimidine (5-Cl-Hpymo); 3: LH=5-bromo-2-hydroxypyrimidine (5-Br-Hpymo); 4: LH=5-iodo-2-hydroxypyrimidine (5-I-Hpymo)) have been obtained from the reaction between cis-protected square-planar [Pt(en)(H(2)O)(2)](2+) metal entities and LH in aqueous media. Additionally, the binding properties of 2, 3, 4 and their congener [{Pt(en)(L)}(4)](4+) (1: LH=2-hydroxypyrimidine (Hpymo)) with calf thymus-DNA (ct-DNA) have been studied by using different techniques including circular and linear dichroism (CD and LD, respectively) and UV-visible absorbance spectroscopies, gel electrophoresis, fluorescence competitive-binding studies and atomic force microscopy (AFM). The results are consistent with significant non-covalent interactions taking place between the polynuclear cyclic species and ct-DNA. Moreover, gel electrophoresis, linear dichroism titrations and AFM images of ct-DNA with metallacalixarenes show ct-DNA coiling at low metallacalixarene concentrations and upon subsequent increments in metallacalixarene concentration ct-DNA can be seen to uncoil with concomitant formation of long and inflexible ct-DNA structures.

A platinum metal complex in which terpyridine joins estradiol (via an ethynyl link) to a platinum with a labile ligand (chloride) has been designed, synthesised and its X-ray crystal structure determined. The aim of this work was to link a targeting motif (in this case estrogen) to a metal-based biomolecule recognition unit (the platinum moiety). The target molecule: 17alpha-[4'-ethynyl-2,2':6',2'-terpyridine]-17beta-estradiol platinum(II) chloride (PtEEtpy) has been shown to bind to both human and bovine serum albumin (SA) and to DNA. FTICR mass spectrometry shows that the bimolecular units are in each case linked through coordination to the platinum with displacement of the chloride ligand. Circular dichroism indicates that a termolecular entity involving PtEEtpy, SA and DNA is formed. A range of electrospray mass spectrometry experiments showed that the PtEEtpy complex breaks and forms coordination bonds relatively easily. A whole cell estrogen receptor assay in an estrogen receptor positive cell (MCF-7) confirms binding of both EEtpy and PtEEtpy to the estrogen receptor in cells. The work demonstrates the concept of linking a targeting moiety (in this case estrogen) to a DNA binding agent.

The DNA binding of a dicationic pyridylimine-based dicopper(I) metallosupramolecular cylinder is reported together with its ability to act as an artificial nuclease. The cylinder binds strongly to DNA; more strongly than the spherical dication [Ru(phen)(3)](2+) (phen=1,10-phenanthroline), but more weakly than the corresponding tetracationic cylinders. DNA coiling effects are not observed with this dication, in contrast to the situation with the previously reported tetracationic cylinder involving a similar ligand. Linear dichroism (LD) data suggests that the dicopper cylinder binds in a different orientation from that of the tetracationic iron cylinder. Furthermore, the dicopper cylinder shows DNA-cleavage activity in the presence of peroxide. Of particular note is that the cylinder displays a marked and unusual ability to cleave both DNA strands at the same site, probably reflecting its dinuclear nature and possibly its mode of binding to the DNA.

In this work we present the results of a molecular simulation study of the interaction between a tetracationic bis iron(II) supramolecular cylinder, [Fe2(C25H20N4)3]4+, and DNA. This supramolecular cylinder has been shown to bind in the major groove of DNA and to induce dramatic coiling of the DNA. The simulations have been designed to elucidate the interactions that lead the cylinder to target the major groove and that drive the subsequent DNA conformational changes. Three sets of multi-nanosecond simulations have been performed: one of the uncomplexed d(CCCCCTTTTTCC) d(GGAAAAAGGGGG) dodecamer; one of this DNA complexed with the cylinder molecule; and one of this DNA complexed with a neutralised version of the cylinder. Coiling of the DNA was observed in the DNA-cylinder simulations, giving insight into the molecular level nature of the supramolecular coiling observed experimentally. The cylinder charge was found not to be essential for the DNA coiling, which implies that the DNA response is moderated by the short range interactions that define the molecular shape. Cylinder charge did, however, affect the integrity of the DNA duplex, to the extent that, under some circumstances, the tetracationic cylinder induced defects in the DNA base pairing at locations adjacent to the cylinder binding site.

A new tetracationic triple-stranded supramolecular cylinder is prepared from a bis(pyridylimine) ligand containing a diphenylmethane and two ketimine groups in the spacer. The cylinder is longer and slightly wider than the corresponding cylinder containing just diphenylmethane spacers. Inter-strand CH...pi interactions are not observed and this affects the relay of the chiral information within the cylinder; a mixture of rac and meso isomers results, with the meso isomer being the dominant solution species and characterised in the solid state by crystallography. This new cylinder does bind to DNA as confirmed by induced circular dichroism signals in both the metal-to-ligand charge transfer (MLCT) and in-ligand bands of the cylinder. Flow linear dichroism demonstrates that the cylinder binds to DNA in a specific orientation(s) and is consistent with (major) groove-binding as seen for the shorter cylinder. Some DNA bending/coiling is observed but the effect is much less dramatic than observed for the cylinder with diphenylmethane spacers confirming that coiling is not solely a consequence of the tetracationic charge, but rather is related to the precise size and shape of the cylinder.

A tetracationic supramolecular cylinder, [Fe(2)L(3)](4+) (L=C(25)H(20)N(4)), with a triple-helical architecture, is just the right size to fit into the major groove of DNA but too big to fit into the minor groove. A detailed NMR spectroscopic analysis supported by molecular dynamics (MD) calculations shows unambiguously the close fit between the cylinder and a duplex oligonucleotide, [d(GACGGCCGTC)(2)]. Furthermore, only the left-handed enantiomer of the cylinder seems to fit the groove geometry. With both free and complexed species of [Fe(2)L(3)](4+) and DNA in solution, the NMR spectra are too complicated for a detailed structure determination. Based on differences in chemical shifts and extensive MD calculations, a realistic qualitative picture of the DNA-cylinder adduct is presented. Several sets of chemical shifts assigned to the protons of the three ligand strands in the cylinder indicate that the iron complex situated in the major groove exhibits restricted rotation on the NMR timescale around the cylindrical axis. The NMR NOE data support a model where the cylinder undergoes both a translational and rotational oscillation in the major groove. The results of an NOE restrained MD calculation indicates that the cylinder induces a 40 degrees bend of the double helix, in accordance with linear dichroism measurements. Other distinct features to be noticed are the very low value of the helical twist (16 degrees) induced at the G(4)C(5) step.

The non-covalent interaction of five novel ruthenium(II) bis-terpyridine complexes with calf thymus DNA and, where appropriate, with poly[d(G-C)](2) and poly[d(A-T)](2) is described. Each complex is functionalised with aryl tail groups in the 4' position of the terpyridine ligands ((i) 9-anthracenyl, (ii) 4,4'-biphenyl, (iii) beta-naphthyl, (iv) 9-phenanthrenyl, and (v) 1-pyrenyl). Circular dichroism and linear dichroism show that the binding of three of the complexes (phenanthrenyl, anthracenyl and pyrenyl) at low metal complex concentration is dominated by intercalation of the aryl tail groups between the DNA bases. The complex with the biphenyl tail predominantly exhibits groove binding with no significant tail intercalation. The naphthyl derivative binds both by intercalation and a non-intercalative mode even at low metal complex concentrations. At high metal complex concentrations, aggregation of the complexes on the DNA is observed. Resonance light scattering indicates that the aggregates are of low nuclearity along the groove.

We have designed a synthetic tetracationic metallo-supramolecular cylinder that targets the major groove of DNA with a binding constant in excess of 10(7) M(-1) and induces DNA bending and intramolecular coiling. The two enantiomers of the helical molecule bind differently to DNA and have different structural effects. We report the characterization of the interactions by a range of biophysical techniques. The M helical cylinder binds to the major groove and induces dramatic intramolecular coiling. The DNA bending is less dramatic for the P enantiomer.

The dinuclear iron(II) supramolecular helicates [Fe2L3]Cl4 (L=C25H20N4) bind to DNA through noncovalent (i.e., hydrogen-bonding, electrostatic) interactions and exhibit antimicrobial and anticancer effects. In this study, we show that the helicates condense plasmid DNA with a much higher potency than conventional DNA-condensing agents. Notably, molecules of DNA in the presence of the M enantiomer of [Fe2L3]Cl4 do not form intermolecular aggregates typically formed by other condensing agents, such as spermidine or spermine. The helicates inhibit the activity of several DNA-processing enzymes, such as RNA polymerase, DNA topoisomerase I, deoxyribonuclease I, and site-specific restriction endonucleases. However, the results also indicate that the DNA condensation induced by the helicates does not play a crucial role in these inhibition reactions. The mechanisms for the inhibitory effects of [Fe2L3]Cl4 helicates on DNA-related enzymatic activities have been proposed. [ABSTRACT FROM AUTHOR]

Abstract: The novel steroidal carrier ligand 17-α-[4′-ethynyl-dimethylbenzylamine]-17-β-testosterone (ET-dmba 1) and the steroid — C,N-chelate platinum(II) derivatives [Pt(ET-dmba)Cl(L)] (L = DMSO (2) and PTA (3; PTA =1,3,5-triaza-7-phosphaadamantane)) have been prepared. Values of IC50 were calculated for the new platinum complexes 2 and 3 against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D). At 48h incubation time complexes 2 and 3 show very low resistance factors (RF of <2) against an A2780 cell line which has acquired resistant to cisplatin and were more active than cisplatin (about 4-fold for 3) in T47D (AR+, AR=androgen receptor). Compound 1 retains a moderate degree of relative binding affinity (RBA=0.94%) for androgen receptors. The cytotoxicity of the non steroidal platinum analogues [Pt(dmba)Cl(L)] (dmba=dimethylbenzylamine; L=DMSO (4) and PTA (5)) has also been studied for comparison purposes. Theoretical calculations at the BP86/def2-TZVP level of theory on complex 3 have been undertaken. [Copyright &y& Elsevier]