👤 Santoro AE

Early in the evolution of life, a proto-metabolic network was encapsulated within a membrane compartment. The permeability characteristics of the membrane determined several key functions of this network by determining which compounds could enter the compartment and which compounds could not. One key feature of known life is the utilization of right-handed d-ribose and d-deoxyribose sugars and left-handed l-amino acid stereochemical isomers (enantiomers); however, it is not clear why life adopted this specific chirality. Generally, archaea have l-phospholipid membrane chemistries and bacteria and eukaryotes have d-phospholipid membrane chemistries. We previously demonstrated that an l-archaeal and a d-intermediate membrane mimic, bearing a mixture of bacterial and archaeal lipid characteristics (a 'hybrid' membrane), displayed increased permeability for several key compounds compared to bacterial-like membranes. Here, we investigate if these membranes can drive stereochemical selection on pentose sugars, hexose sugars, and amino acids. Using permeability assays of homogenous unilamellar vesicles, we demonstrate that both membranes select for d-ribose and d-deoxyribose sugars while the hybrid membrane uniquely selects for a reduced alphabet of l-amino acids. This repertoire includes alanine, the plausible first l-amino acid utilized. We conclude such compartments could provide stereochemical compound selection matching those used by the core metabolism of life. Show less

Modern quantitative image analysis techniques have enabled high-throughput, high-content imaging experiments. Image-based profiling leverages the rich information in images to identify similarities or differences among biological samples, rather than measuring a few features, as in high-content screening. Here, we review a decade of advancements and applications of Cell Painting, a microscopy-based cell-labeling assay aiming to capture a cell's state, introduced in 2013 to optimize and standardize image-based profiling. Cell Painting's ability to capture cellular responses to various perturbations has expanded owing to improvements in the protocol, adaptations for different perturbations, and enhanced methodologies for feature extraction, quality control, and batch-effect correction. Cell Painting is a versatile tool that has been used in various applications, alone or with other -omics data, to decipher the mechanism of action of a compound, its toxicity profile, and other biological effects. Future advances will likely involve computational and experimental techniques, new publicly available datasets, and integration with other high-content data types. Show less

One of the deepest branches in the tree of life separates the Archaea from the Bacteria. These prokaryotic groups have distinct cellular systems including fundamentally different phospholipid membrane bilayers. This dichotomy has been termed the lipid divide and possibly bestows different biophysical and biochemical characteristics on each cell type. Classic experiments suggest that bacterial membranes (formed from lipids extracted from Escherichia coli, for example) show permeability to key metabolites comparable to archaeal membranes (formed from lipids extracted from Halobacterium salinarum), yet systematic analyses based on direct measurements of membrane permeability are absent. Here, we develop a new approach for assessing the membrane permeability of approximately 10 μm unilamellar vesicles, consisting of an aqueous medium enclosed by a single lipid bilayer. Comparing the permeability of 18 metabolites demonstrates that diether glycerol-1-phosphate lipids with methyl branches, often the most abundant membrane lipids of sampled archaea, are permeable to a wide range of compounds useful for core metabolic networks, including amino acids, sugars, and nucleobases. Permeability is significantly lower in diester glycerol-3-phosphate lipids without methyl branches, the common building block of bacterial membranes. To identify the membrane characteristics that determine permeability, we use this experimental platform to test a variety of lipid forms bearing a diversity of intermediate characteristics. We found that increased membrane permeability is dependent on both the methyl branches on the lipid tails and the ether bond between the tails and the head group, both of which are present on the archaeal phospholipids. These permeability differences must have had profound effects on the cell physiology and proteome evolution of early prokaryotic forms. To explore this further, we compare the abundance and distribution of transmembrane transporter-encoding protein families present on genomes sampled from across the prokaryotic tree of life. These data demonstrate that archaea tend to have a reduced repertoire of transporter gene families, consistent with increased membrane permeation. These results demonstrate that the lipid divide demarcates a clear difference in permeability function with implications for understanding some of the earliest transitions in cell origins and evolution. Show less

Title: New ruthenium(II) complexes with cyclic thio- and semicarbazone: evaluation of cytotoxicity and effects on cell migration and apoptosis of lung cancer cells. Abstract: We describe the synthesis, physicochemical characterization, and in vitro antitumor assays of four novel analogous ruthenium(II) complexes with general formula cis-[RuII(N-L)(P-P)2]PF6, where P-P = bis(diphenylphosphine)methane (dppm, in complexes 1 and 2) or bis(diphenylphosphine)ethane (dppe, in complexes 3 and 4) and N-L = 5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione (Btsc, in complexes 1 and 3) or 5,6-diphenyltriazine-3-one (Bsc, in complexes 2 and 4). The data were consistent with cis arrangement of the biphosphine ligands. For the Btsc and Bsc ligands, the data pointed to monoanionic bidentate coordination to ruthenium(II) through N,S and N,O, respectively. Single-crystal X-ray diffraction showed that complex 1 crystallized in the monoclinic system, space group P21/c. Determination of the cytotoxicity profiles of complexes 1-4 gave SI values ranging from 1.19 to 3.50 against the human lung adenocarcinoma cell line A549 and the non-tumor lung cell line MRC-5. Although the molecular docking studies suggested that the interaction between DNA and complex 4 was energetically favorable, the experimental results showed that they interacted weakly. Overall, our results demonstrated that these novel ruthenium(II) complexes have interesting in vitro antitumor potential and this study may contribute to further studies in medicinal inorganic chemistry. Show less

In this work we present the synthesis and characterization of six new ruthenium compounds with general formulae [Ru(L)(dppb)(bipy)]PF₆ and [Ru(L)(dppe)₂]PF₆ where L = salicylic acid (Sal), 4-aminosalicylic acid (AmSal) or 2,4-dihydroxybenzoic acid (DiSal), dppb = 1,4-bis(diphenylphosphino)butane, dppe = 1,2-bis(diphenylphosphino)ethane and bipy = 2,2'-bipyridine. The complexes were characterized by elemental analysis, molar conductivity, cyclic voltammetry, NMR, UV-vis and IR spectroscopies, and two by X-ray crystallography. The ³¹P{¹H} NMR spectra of the complexes with the general formula [Ru(L)(dppe)₂]PF₆ showed that the phosphorus signals are solvent-dependent. Aprotic solvents, which form strong hydrogen bonds with the complexes, inhibit the free rotation of the salicylic acid-based, modifying the diphosphine cone angles, leading to distortion of the phosphorus signals in the NMR spectra. The cytotoxicity of the complexes was evaluated in MCF-7, MDA-MB-231, SKBR3 human breast tumor cells, and MCF-10 non-tumor cell lines. The complexes with the structural formula [Ru(L)(dppe)₂]PF₆ were the most cytotoxic, and the complex [Ru(AmSal)(dppe)₂]PF₆ with L = 4-aminosalicylic acid ligand was the most selective for the MDA-MB-231 cell line. This complex interacts with the transferrin and induces apoptosis through the intrinsic pathway, as demonstrated by increased levels of proteins involved in apoptotic cell death. Show less

Title: Cytotoxicity evaluation and DNA interaction of Ru Abstract: Although there are various treatment options for cancer, this disease still has caused an increasing number of deaths, demanding more efficient, selective and less harmful drugs. Several classes of ruthenium compounds have been investigated as metallodrugs for cancer, mainly after the entry of imidazolH [trans-RuCl4-(DMSO-S)(imidazole)] (NAMI-A) and indazolH [trans-RuCl4-(Indazol)2] (KP1019) in clinical trials. In this sense, RuII complexes with general formula [Ru(L1-3)(bipy)2]PF6 (1-3) (L1 = ethyl 3-(6-methyl-2-oxo-2H-chromen-3-yl)-3-oxopropanoate, L2 = ethyl 3-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-3-oxopropanoate, L3 = ethyl 3-(8-methoxy-2-oxo-2H-chromen-3-yl)-3-oxopropanoate and bipy = bipyridine) have been synthesized. The crystal structure of 2 revealed that the RuII atom lies on a distorted octahedral geometry with the deprotonated ligand (L2-) coordinated through β-ketoester group oxygen atoms. In vitro cytotoxic activity of the compounds was evaluated against 4T1 (murine mammary carcinoma) and B16-F10 (murine metastatic melanoma) tumor cells, and the non-tumor cell line BHK-21 (baby hamster kidney). Coordination with RuII resulted in expressive enhancement of cytotoxic activity. The precursors were inactive below 100 μM and the final RuII complexes (1-3) showed IC50 ranging from 2.0 to 12.8 μM; 2 being the most potent compound. DNA interaction studies revealed a greater capacity of the complexes to interact with DNA than the ligands, where, 2 exhibited the highest Kb constant of 2.2 × 104 M-1. Fluorescence investigation demonstrated that 1-3 are capable of quenching the fluorescence emission of the EtdBr-DNA complex up to 40%. Molecular docking showed that the interaction of 1-3 between the DNA base pairs from the coumarin portion was with scores of 67.28, 68.62 and 64.88, respectively, and 75.45 for ellipticine, suggesting an intercalative mode of binding. Our findings show that the RuII complexes are eligible for continuing to be investigated as potential antitumor compounds. Show less

This work describes the synthesis of three new ruthenium(ii) complexes with gallic acid and derivatives of the general formula [Ru(L)(dppb)(bipy)]PF₆, where L = gallate (GAC), benzoate (BAC), and esterified-gallate (EGA), bipy = 2,2'-bipyridine and dppb = 1,4-bis(diphenylphosphino)butane. The complexes were characterized by elemental analysis, molar conductivity, NMR, cyclic voltammetry, UV-vis and IR spectroscopy, and two of them by X-ray crystallography. Cell viability assays show promising results, indicating higher cytotoxicity of the complexes in MDA-MB-231 cells, a triple-negative breast cancer (TNBC) cell line, compared with the hormone-dependent MCF-7 cell line. Studies in vitro with the MDA-MB-231 cell line showed that only Ru(BAC) and Ru(GAC) interacted with BSA. Besides that, the Ru(GAC) complex, which has a polyphenolic acid, interacted in an apo-Tf structure and function dependent manner and it was able to inhibit the formation of reactive oxygen species. Ru(GAC) was able to cause damage to the cellular cytoskeleton leading to inhibition of some cellular processes of TNBC cells, such as invasion, migration, and adhesion. Show less

In this work, we present the synthesis and characterization of five new ruthenium compounds with general formula [Ru(L)(dppb)(bipy)]PF₆, where L = cinnamic acid derivatives, dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine. The cytotoxicity of the complexes was evaluated against human breast tumor cells from the lines MCF-7, MDA-MB-231 and in human (MCF-10A) or mouse (L929) non-tumor cells. Complexes Ru(L₄)(dppb)(bipy)]PF₆ (4) (L₄ = 4-hydroxycinnamic acid) and [Ru(L₅)(dppb)(bipy)]PF₆ (5) (L₅ = 3,4-dihydroxycinnamic acid) were the most selective, presenting the highest values of selectivity indexes besides inhibited some processes related to tumor progression in vitro, such as invasion, migration, and adhesion in the MDA-MB-231 cell line. In addition, the complexes 4 and 5 were able to interact with Bovine Serum Albumin (BSA) and complex 5 showed antioxidant activity. Show less

The triple-negative breast cancer subtype (TNBC) is highly aggressive and metastatic and corresponds to 15-20% of diagnosed cases. TNBC treatment is hampered, because these cells usually do not respond to hormonal therapy, and they develop resistance to chemotherapeutic drugs. On the other hand, the severe side effects of cisplatin represent an obstacle for its clinical use. Ruthenium (Ru)-based complexes have emerged as promising antitumor and antimetastatic substitutes for cisplatin. In this study, we demonstrated the effects of a Ru/biphosphine complex, containing gallic acid (GA) as a ligand, [Ru(GA)(dppe)₂]PF₆, hereafter called Ru(GA), on a TNBC cell line, and compared them to the effects in a nontumor breast cell line. Ru(GA) complex presented selective cytotoxicity against TNBC over nontumor cells, inhibited its migration and invasion, and induced apoptosis. These effects were associated with the increased amount of transferrin receptors (TfR) on tumor cells, compared to nontumor ones. Silencing of TfR decreased Ru(GA) effects on TNBC cells, demonstrating that these receptors were at least partially responsible for Ru(GA) delivery into tumor cells. The Ru(GA) compound must be further studied in different in vivo assays in order to investigate its antitumor properties and its toxicity in complex biological systems. Show less

Metallo prodrugs that take advantage of the inherent acidity surrounding cancer cells have yet to be developed. We report a new class of pH-activated metallo prodrugs (pHAMPs) that are activated by light- and pH-triggered ligand dissociation. These ruthenium complexes take advantage of a key characteristic of cancer cells and hypoxic solid tumors (acidity) that can be exploited to lessen the side effects of chemotherapy. Five ruthenium complexes of the type [(N,N)₂Ru(PL)]²⁺ were synthesized, fully characterized, and tested for cytotoxicity in cell culture (1_A: N,N = 2,2'-bipyridine (bipy) and PL, the photolabile ligand, = 6,6'-dihydroxybipyridine (6,6'-dhbp); 2_A: N,N = 1,10-phenanthroline (phen) and PL = 6,6'-dhbp; 3_A: N,N = 2,3-dihydro-[1,4]dioxino[2,3-f][1,10]phenanthroline (dop) and PL = 6,6'-dhbp; 4_A: N,N = bipy and PL = 4,4'-dimethyl-6,6'-dihydroxybipyridine (dmdhbp); 5_A: N,N = 1,10-phenanthroline (phen) and PL = 4,4'-dihydroxybipyridine (4,4'-dhbp). The thermodynamic acidity of these complexes was measured in terms of two pK_a values for conversion from the acidic form (X_A) to the basic form (X_B) by removal of two protons. Single-crystal X-ray diffraction data is discussed for 2_A, 2_B, 3_A, 4_B, and 5_A. All complexes except 5_A showed measurable photodissociation with blue light (λ = 450 nm). For complexes 1_A-4_A and their deprotonated analogues (1_B-4_B), the protonated form (at pH 5) consistently gave faster rates of photodissociation and larger quantum yields for the photoproduct, [(N,N)₂Ru(H₂O)₂]²⁺. This shows that low pH can lead to greater rates of photodissociation. Cytotoxicity studies with 1_A-5_A showed that complex 3_A is the most cytotoxic complex of this series with IC₅₀ values as low as 4 μM (with blue light) versus two breast cancer cell lines. Complex 3_A is also selectively cytotoxic, with sevenfold higher toxicity toward cancerous versus normal breast cells. Phototoxicity indices with 3_A were as high as 120, which shows that dark toxicity is avoided. The key difference between complex 3_A and the other complexes tested appears to be higher uptake of the complex as measured by inductively coupled plasma mass spectrometry, and a more hydrophobic complex as compared to 1_A, which may enhance uptake. These complexes demonstrate proof of concept for dual activation by both low pH and blue light, thus establishing that a pHAMP approach can be used for selective targeting of cancer cells. Show less

The complexes cis-[Ru(quin)(dppm)₂]PF₆ and cis-[Ru(kynu)(dppm)₂]PF₆ (quin = quinaldate; kynu = kynurenate; dppm = bis(diphenylphosphino)methane) were prepared and characterized by elemental analysis, electronic, FTIR, ¹H, and ³¹P{¹H} NMR spectroscopies. Characterization data were consistent with a cis arrangement for the dppm ligands and a bidentate coordination through carboxylate oxygens of the quin and kynu anions. These complexes were not able to intercalate CT-DNA as shown by circular dichroism spectroscopy. On the other hand, bovine serum albumin (BSA) binding constants and thermodynamic parameters suggest spontaneous interactions with this protein by hydrogen bonds and van der Waals forces. Cytotoxicity assays were carried out on a panel of human cancer cell lines including HepG2, MCF-7, and MO59J and one normal cell line GM07492A. In general, the new ruthenium(II) complexes displayed a moderate to high cytotoxicity in all the assayed cell lines with IC₅₀ ranging from 10.1 to 36 µM and were more cytotoxic than the precursor cis-[RuCl₂(dppm)₂]. The cis-[Ru(quin)(dppm)₂]PF₆ were two to three times more active than the reference metallodrug cisplatin in the MCF-7 and MO59J cell lines. Show less

Thirteen new ruthenium amino acid complexes were synthesized and characterized. They were obtained by the reaction of α-amino acids (AA) with [RuCl₂(P-P)(N-N)], where P-P=1,4-bis(diphenylphosphino)butane (dppb) or 1,3-bis(diphenylphosphino)propane (dppp) and N-N=4,4'-dimethyl-2,2'-bipyridine (4'-Mebipy), 5,5'-dimethyl-2,2'-bipyridine (5'-Mebipy) or 4,4'-Methoxy-2-2'-bipyridine (4'-MeObipy). This afforded a family of complexes formulated as [Ru(AA-H)(P-P)(N-N)]PF₆, where AA=glycine (Gly), L-alanine (Ala), L-valine (Val), L-tyrosine (Tyr), L-tryptophan (Trp), L-histidine (His) and L-methionine (Met). All compounds were characterized by elemental analysis, spectroscopic and electrochemical techniques. The [Ru(AA-H)(P-P)(N-N)]PF₆ complexes are octahedral (the AA-H ligand binding involves N-amine and O-carboxylate), diamagnetic (low-spin d⁶, S=0) and present bands due to electronic transitions in the visible region. ¹H, ¹³C{¹H} and ³¹P{¹H} NMR spectra of the complexes indicate the presence of C₂ symmetry, and the identification of diastereoisomers. In vitro cytotoxicity assays of the compounds and cisplatin were carried out using MDA-MB-231 (human breast) tumor cell line and a non-tumor breast cell line (MCF-10A). Most complexes present promising results with IC₅₀ values comparable with the reference drug cisplatin and high selectivity indexes were found for the complexes containing L-Trp. The binding of two Ru-precursors of the type [RuCl₂(dppb)(NN)] (N-N=4'-MeObipy or 4'-Mebipy) to the blood transporter protein human serum albumin (HSA) was evaluated by fluorescence and circular dichroism spectroscopy. Both complexes bind HSA, probably in the hydrophobic pocket near Trp214, and the Ru-complex containing 4'-MeObipy shows higher affinity for HSA than the 4'-Mebipy one. Show less

Three new mixed and mononuclear Ru(II) complexes containing 1,3-thiazolidine-2-thione (tzdtH) were synthesized and characterized by spectroscopic analysis, molar conductivity, cyclic voltammetry, high-resolution electrospray ionization mass spectra and X-ray diffraction. The complexes presented unique stereochemistry and the proposed formulae are: [Ru(tzdt)(bipy)(dppb)]PF6 (1), cis-[Ru(tzdt)2(PPh3)2] (2) and trans-[Ru(tzdt)(PPh3)2(bipy)]PF6 (3), where dppb=1,4-bis(diphenylphosphino)butane and bipy=2,2'-bipyridine. These complexes demonstrated strong cytotoxicity against cancer cell lines when compared to cisplatin. Specifically, complex 2 was the most potent cytotoxic agent against MCF-7 breast cells, while complexes 1 and 3 were more active in DU-145 prostate cells. Binding of complexes to ctDNA was determined by UV-vis titration and viscosity measurements and revealed binding constant (Kb) values in range of 1.0-4.9×10(3)M(-1), which are characteristic of compounds possessing weak affinity to ctDNA. In addition, these complexes presented antiparasitic activity against Trypanosoma cruzi. Specifically, complex 3 demonstrated strong potency, moderate selectivity index and acted in synergism with the approved antiparasitic drug, benznidazole. Additionally, complex 3 caused parasite cell death through a necrotic process. In conclusion, we demonstrated that Ru(II) complexes have powerful pharmacological activity, while the metal-free tzdtH does not provoke the same outcome. Show less

The synthesis and spectroscopic characterization of nine π-arene piano-stool ruthenium (II) complexes with aromatic dinitrogen chelating ligands or containing chloroquine (CQ), are described in this study: [Ru(η(6)-C10H14)(phen)Cl]PF6 (1), [Ru(η(6)-C10H14)(dphphen)Cl]PF6 (2), [Ru(η(6)-C10H14)(bipy)Cl]PF6 (3), [Ru(η(6)-C10H14)(dmebipy)Cl]PF6 (4) and [Ru(η(6)-C10H14)(bdutbipy)Cl]PF6 (5), [Ru(η(6)-C10H14)(phen)CQ](PF6)2 (6), [Ru(η(6)-C10H14)(dphphen)CQ](PF6)2 (7), [Ru(η(6)-C10H14)(bipy)CQ](PF6)2 (8), [Ru(η(6)-C10H14)(dmebipy)CQ](PF6)2 (9): [1,10-phenanthroline (phen), 4,7-diphenyl-1,10-phenanthroline (dphphen), 2,2'-bipyridine (bipy), 5,5'-dimethyl-2,2'-bipyridine (dmebipy), and 4,4'-di-t-butyl-2,2'-bipyridine (dbutbipy)]. The solid state structures of five ruthenium complexes (1-5) were determined by X-ray crystallography. Electrochemical experiments were performed by cyclic voltammetry to estimate the redox potential of the Ru(II)/Ru(III) couple in each case. Their interactions with DNA and BSA, and activity against four cell lines (L929, A549, MDA-MB-231 and MCF-7) were evaluated. Compounds 2, 6 through 9, interact with DNA which was comparable to the one observed for free chloroquine. The results of fluorescence titration revealed that these complexes strongly quenched the intrinsic fluorescence of BSA following a static quenching procedure. Binding constants (Kb) and the number of binding sites (n~1) were calculated using modified Stern-Volmer equations. The thermodynamic parameters ΔG at different temperatures were calculated and subsequently the values of ΔH and ΔS were also calculated, which revealed that hydrophobic and electrostatic interactions play a major role in the BSA-complex association. The MTT assay results indicated that complexes 2, 5 and 7 showed cytostatic effects at appreciably lower concentrations than those needed for cisplatin, chloroquine and doxorubicin. Show less

Six novel ruthenium(II)- and osmium(II)-arene complexes with three modified indolo[3,2-c]quinolines have been synthesized in situ starting from 2-aminoindoloquinolines and 2-pyridinecarboxaldehyde in the presence of [M(p-cymene)Cl(2)](2) (M = Ru, Os) in ethanol. All complexes have been characterized by elemental analysis, spectroscopic techniques ((1)H, (13)C NMR, IR, UV-vis), and ESI mass spectrometry, while four complexes were investigated by X-ray diffraction. The complexes have been tested for antiproliferative activity in vitro in A549 (non-small cell lung), SW480 (colon), and CH1 (ovarian) human cancer cell lines and showed IC(50) values between 1.3 and >80 μM. The effects of Ru vs Os and modifications of the lactam unit on intermolecular interactions, antiproliferative activity, and cell cycle are reported. One ruthenium complex and its osmium analogue have been studied for anticancer activity in vivo applied both intraperitoneally and orally against the murine colon carcinoma model CT-26. Interestingly, the osmium(II) complex displayed significant growth-inhibitory activity in contrast to its ruthenium counterpart, providing stimuli for further investigation of this class of compounds as potential antitumor drugs. Show less

The intrinsic factor (IF) vitamin B(12) ileum anchored receptor, cubilin, mediates endocytotic uptake of the IF complex of vitamin B(12) to the blood serum. This receptor was targeted for the selective delivery and accumulation of a new bioprobe, a B(12) conjugate of rhenium 2, in the cubilin expressing placental choriocarcinoma BeWo cell line. Competitive uptake and cytotoxicity assays of 2 were investigated and interactions with nuclear DNA explored. In addition, the mechanism of internalization of 2 was confirmed to proceed in an IF-cubilin mediated fashion via siRNA transfection experiments. These studies show the great potential of cubilin as a new target for the delivery of B(12) based conjugates for cancer diagnostics and/or treatment. Show less

The synthesis, characterization, in vitro imaging, and cytotoxic properties of a new folate conjugate of rhenium(I) are reported. The conjugate [FA-PEG-BQAV-Re(CO)3]+ (gamma-4) was screened against an adriamycin- and cisplatin-resistant human ovarian cancer cell line (A2780/AD) that overexpresses the folate receptor (FR). Compound gamma-4 was internalized by a folate-receptor-mediated endocytotic pathway, which results in internal accumulation of gamma-4. This was contrasted with a FR-negative Chinese hamster ovary cell line in which no internalization of gamma-4 was observed. gamma-4 was found to be cytotoxic with IC(50) values of 189 and 78 microM at 6 and 24 h, respectively, toward the FR-positive cell line. This is in contrast to the IC(50) value of 502 microM at 6 h and 84 microM at 24 h for cisplatin in the same cell line, with a significantly greater toxicity at the earlier time point. The cytotoxicity of gamma-4 as explained by interactions that occur between the rhenium(I) complex moiety and DNA is described. Show less