The role of intermolecular interactions in [Fe(X-salEen)2]ClO4 spin crossover complexes.

Two new spin crossover (SCO) Fe(III) compounds were prepared, their structures were analysed and their magnetic properties were investigated. An exhaustive analysis of the effects of halogen substitution and aromatic ring functionalisation on the magnetic properties of non-solvated Fe(III) perchlorate complexes has been performed. Through comparative analysis, different magnetic profiles were found for the compounds studied, namely F (1), Cl (2), H (3), Br (4a, 4b), and I (5). Using tools like Hirshfeld analysis, the study revealed patterns in octahedral distortions and deviations from the ideal octahedral geometry. The SCO phenomenon as the conducting wire in this study, emphasises the influence of intermolecular interactions on the low spin (LS) to high spin (HS) transitions in these halogen-substituted complexes. The prevalence of H⋯H contributions has been demonstrated, albeit being the weakest and an inverse strength relationship in H⋯X interactions ranging from F to I. The findings not only interpret the intricate balance between halogen substitution, functionalisation, and intermolecular interactions in modulating magnetic properties but also direct future works in designing similar molecular systems.

Unravelling the binding affinity and selectivity of molybdenum(II) phenanthroline complexes with DNA G-quadruplexes by using linear-scaling DFT studies. The important role of ancillary ligands.

We have used near linear-scaling density functional theory (LS-DFT) methods including dispersion, for the first time, to study the interaction of two isomers, equatorial (Eq) and axial (Ax), of the [Mo(η3-C3H5)Br(CO)2(phen)] metal complex with the DNA G-quadruplexes (GQ) to gain insight into its cytotoxicity. The LMKLL/DZDP level of calculation, which includes van der Waals contributions, with the SIESTA software was used to treat by means of first-principles computations the whole biological studied model system with ∼1000 atoms. Computed formation energies point to systems containing the Ax isomer as the most stable although the nearest system in energy containing the Eq isomer is only 7.5 kcal mol-1 above. On the other hand, the energy decomposition analysis (EDA) favours interaction energies for the systems containing the Eq isomer. However, when solvent effects are taken into account the systems containing the Ax isomer are again the most stable. This Ax isomer was found interacting by means of end-stacking with the GQ and surprisingly totally inside the non-canonical secondary structure, where all the ligands of the metal complex produce several weak interactions with the DNA structure. On the other hand, the Eq isomer prefers to interact from outside by means of intercalation in which the ancillary ligands also have some role in the interaction. Such features and comparison with the results regarding the interaction of the [Mo(η3-C3H5)Br(CO)2(phen)] metal complex with duplex DNA suggest that the [Mo(η3-C3H5)Br(CO)2(phen)] would have a higher affinity and eventual selectivity for non-canonical DNA GQ structures.

Relationship between structure and cytotoxicity of vanadium and molybdenum complexes with pyridoxal derived ligands.

In this work four vanadium complexes (compounds 1, 2, 3 and 4) and one molybdenum complex (compound 5) with hydrazone ligands derived from pyridoxal were synthesized and characterized. All compounds are mononuclear species, two of them (compounds 3 and 5) are dioxide complexes and the other three (compounds 1, 2 and 4) monoxide complexes. The vanadium atom of the compound 3 is five-coordinated and all the other compounds have a six coordinated environment polyhedron. The poses for the potential intercalation of the compounds 2 and 3 with DNA were obtained by using AutoDock software. Optimizations were also performed at PM6-D3H4 semi-empirical level whereas the study of the nature of the interaction was carried out by means of the Energy Decomposition Analysis and the Non-Covalent Interaction index by using in both cases Density Functional Theory computations. The cytotoxicity in lung cancer cells (A549 cell line) of all the compounds was also evaluated. After 24 h of treatment, vanadium complexes showed high values of IC50, between 419.93 ± 22.58 and 685.88 ± 46.55 µM. After 48 h, the results showed that the compound 3 had the lowest IC50 value, 65.32 ± 9.95 µM, and the compound 2 the highest value, 375.28 ± 32.09 µM. The molybdenum complex showed the lowest IC50 value at 48 h (11.22 ± 1.34 µM). The toxicity of the compounds 3, 4 and 5 was tested in vivo, using zebrafish model, and the molybdenum complex showed higher toxic effects than the studied vanadium complexes.

Computational Modelling of the Interactions Between Polyoxometalates and Biological Systems.

Polyoxometalates (POMs) structures have raised considerable interest for the last years in their application to biological processes and medicine. Within this area, our mini-review shows that computational modelling is an emerging tool, which can play an important role in understanding the interaction of POMs with biological systems and the mechanisms responsible of their activity, otherwise difficult to achieve experimentally. During recent years, computational studies have mainly focused on the analysis of POM binding to proteins and other systems such as lipid bilayers and nucleic acids, and on the characterization of reaction mechanisms of POMs acting as artificial metalloproteases and phosphoesterases. From early docking studies locating binding sites, molecular dynamics (MD) simulations have allowed to characterize the nature of POM···protein interactions, and to evaluate the effect of the charge, size, and shape of the POM on protein affinity, including also, the atomistic description of chaotropic character of POM anions. Although these studies rely on the interaction with proteins and nucleic acid models, the results could be extrapolated to other biomolecules such as carbohydrates, triglycerides, steroids, terpenes, etc. Combining MD simulations with quantum mechanics/molecular mechanics (QM/MM) methods and DFT calculations on cluster models, computational studies are starting to shed light on the factors governing the activity and selectivity for the hydrolysis of peptide and phosphoester bonds catalysed by POMs.

Semi-empirical and linear-scaling DFT methods to characterize duplex DNA and G-quadruplexes in the presence of interacting small molecules.

The computational study of DNA and its interaction with ligands is a highly relevant area of research, with significant consequences for developing new therapeutic strategies. However, the computational description of such large and complex systems requires considering interactions of different types simultaneously in a balanced way, such as non-covalent weak interactions (namely hydrogen bonds and stacking), metal-ligand interactions, polarisation and charge transfer effects. All these considerations imply a real challenge for computational chemistry. The possibility of studying large biological systems using quantum methods for the entire system requires significant computational resources, with improvements in parallelisation and optimisation of theoretical strategies. Computational methods, such as Linear-Scaling Density Functional Theory (LS-DFT) and DLPNO-CCSD(T), may allow performing ab initio quantum mechanics calculations, including the electronic structure for large biological systems, in a reasonable computing time. In this work, we study the interaction of small molecules and cations with DNA (both duplex DNA and G-quadruplexes), comparing different computational methods: a LS-DFT method at the LMKLL/DZDP level of theory, semi-empirical methods (PM6-DH2 and PM7), mixed QM/MM, and DLPNO-CCSD(T). Our goal is to demonstrate the adequacy of LS-DFT to treat the different types of interactions present in DNA-dependent systems. We show that LMKLL/DZDP using SIESTA can yield very accurate geometries and energetics in all the different systems considered in this work: duplex DNA (dDNA), phenanthroline intercalating dDNA, G-quadruplexes, and metal-G-tetrads considering alkaline metals of different sizes. As far as we know, this is the first time that full G-quadruplex geometry optimisations have been carried out using a DFT method thanks to its linear-scaling capabilities. Moreover, we show that LS-DFT provides high-quality structures, and some semi-empirical Hamiltonians can also yield suitable geometries. However, DLPNO-CCSD(T) and LS-DFT are the only methods that accurately describe interaction energies for all the systems considered in our study.

Greener Strategy for Lupanine Purification from Lupin Bean Wastewaters Using a Molecularly Imprinted Polymer.

Lupanine is an alkaloid used in the pharma industry as a building block or precursor in the synthesis of sparteine and also explored for drug synthesis in the pharma industry as a chiral selector. This alkaloid is found in lupin bean processing wastewaters originated from the debittering process to make these beans edible. In this work, a computational chemistry approach was taken to design molecularly imprinted polymers (MIPs) selecting itaconic acid, a biobased building block, as a functional monomer that can provide higher affinities for lupanine. MIP-1 was prepared using lupanine as the template, itaconic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linker by bulk polymerization. Lupanine was concentrated from lupin bean wastewater by nanofiltration, extracted with ethyl acetate, and purified using the synthesized MIP. MIP-1 was able to selectively recognize lupanine and improve the purity of lupanine from 78 to 88%, with 82% recovery of the alkaloid. These results show the potential application of this strategy to render the industrial process more sustainable.

Influence of conventional hydrogen bonds in the intercalation of phenanthroline derivatives with DNA: The important role of the sugar and phosphate backbone.

The influence of hydrogen bonds in model intercalated systems between guanine-cytosine and adenine-thymine DNA base pairs (bps) was analyzed with the popular intercalator 1,10-phenanthroline (phen) and derivatives obtained by substitution with OH and NH2 groups in positions 4 and 7. Semiempirical and Density Functional Theory (DFT) methods were used both including dispersion effects: PM6-DH2, M06-2X and B3LYP-D3 along with the recently developed near linear-scaling coupled cluster method DLPNO-CCSD(T) for benchmark calculations. Our results given by QTAIM and non-covalent interaction analysis confirmed the existence of hydrogen bonds created by OH and NH2 . The trends in the energy decomposition analysis for the interaction energy, ΔEint , showed that the ΔEelstat contributions are equal or even a little bit higher than the values for ΔEdisp . Such important ΔEelstat attractive contribution comes mainly from the conventional hydrogen bonds formed by OH and NH2 functional groups with DNA not only with bps but specially with the sugar and phosphate backbone. This behavior is very different from that of phen and other classical intercalators that cannot form conventional hydrogen bonds, where the ΔEdisp is the most important attractive contribution to the ΔEint . The inclusion of explicit water molecules in molecular dynamics simulations showed, as a general trend, that the hydrogen bonds with the bps disappear during the simulations but those with the sugar and phosphate backbone remain in time, which highlights the important role of the sugar and phosphate backbone in the stabilization of these systems.

Growth and analysis of the tetragonal (ST12) germanium nanowires.

New semiconducting materials, such as state-of-the-art alloys, engineered composites and allotropes of well-established materials can demonstrate unique physical properties and generate wide possibilities for a vast range of applications. Here we demonstrate, for the first time, the fabrication of a metastable allotrope of Ge, tetragonal germanium (ST12-Ge), in nanowire form. Nanowires were grown in a solvothermal-like single-pot method using supercritical toluene as a solvent, at moderate temperatures (290-330 °C) and a pressure of ∼48 bar. One-dimensional (1D) nanostructures of ST12-Ge were achieved via a self-seeded vapour-liquid-solid (VLS)-like paradigm, with the aid of an in situ formed amorphous carbonaceous layer. The ST12 phase of Ge nanowires is governed by the formation of this carbonaceous structure on the surface of the nanowires and the creation of Ge-C bonds. The crystalline phase and structure of the ST12-Ge nanowires were confirmed by X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM) and Raman spectroscopy. The nanowires produced displayed a high aspect ratio, with a very narrow mean diameter of 9.0 ± 1.4 nm, and lengths beyond 4 µm. The ST12-Ge nanowire allotrope was found to have a profound effect on the intensity of the light emission and the directness of the bandgap, as confirmed by a temperature-dependent photoluminescence study.

From groove binding to intercalation: unravelling the weak interactions and other factors modulating the modes of interaction between methylated phenanthroline-based drugs and duplex DNA.

Several antitumor drugs base their cytotoxicity on their capacity to intercalate between base pairs of DNA. Nevertheless, it has been established that the mechanism of intercalation of drugs in DNA starts with the prior groove binding mode of interaction of the drug with DNA. Sometimes, for some kind of flat small molecules, groove binding does not produce any cytotoxic effect and the fast transition of such flat small molecules to the cytotoxic intercalation mode is desirable. This is the case of methylated phenanthroline (phen) derivatives, where, changes in the substitution in the position and number of methyl groups determine their capability as cytotoxic compounds and, therefore, it is a way for the modulation of cytotoxic effects. In this work, we studied this modulation by means of the interaction of the [Pt(en)(phen)]2+ complex and several derivatives by methylation of phen in different number and position and the d(GTCGAC)2 DNA hexamer via groove binding using PM6-DH2 and DFT-D methods. The analysis of the geometries, electronic structure and energetics of the studied systems was compared to experimental works to gain insight into the relation structure-interaction for the studied systems with cytotoxicity. The trends are explained by means of the Non-Covalent Interaction (NCI) index, the Energy Decomposition Analysis (EDA) and solvation contributions. Our results are in agreement with the experiments, in which the methylation of position 4 of phen seems to favour the interaction via groove binding thus making the transition to the intercalation cytotoxic mode difficult. Looking at the NCI results, these interactions come not only from the CH/π and CH/n interactions of the methyl group in position 4 but also from the ethylenediamine (en) ligand, whose orientation in the Pt complex was found in such a way that it produces a high number of weak interactions with DNA, especially with the sugar and phosphate backbone.

New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes.

This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns about bacterial antibiotic resistance, this medical strategy is also being explored in this field. Up to three strategies for the use of DNA as target have been studied in our research lines during the last few years: (1) the intercalation of phenanthroline derivatives with duplex DNA; (2) the interaction of metal complexes containing phenanthroline with G-quadruplexes; and (3) the activity of Mo polyoxometalates and other Mo-oxo species as artificial phosphoesterases to catalyze the hydrolysis of phosphoester bonds in DNA. We demonstrate some promising computational results concerning the favorable interaction of these small molecules with DNA that could correspond to cytotoxic effects against tumoral cells and microorganisms. Therefore, our results open the door for the pharmaceutical and medical applications of the compounds we propose.

A Review of Self-Seeded Germanium Nanowires: Synthesis, Growth Mechanisms and Potential Applications.

Ge nanowires are playing a big role in the development of new functional microelectronic modules, such as gate-all-around field-effect transistor devices, on-chip lasers and photodetectors. The widely used three-phase bottom-up growth method utilising a foreign catalyst metal or metalloid is by far the most popular for Ge nanowire growth. However, to fully utilise the potential of Ge nanowires, it is important to explore and understand alternative and functional growth paradigms such as self-seeded nanowire growth, where nanowire growth is usually directed by the in situ-formed catalysts of the growth material, i.e., Ge in this case. Additionally, it is important to understand how the self-seeded nanowires can benefit the device application of nanomaterials as the additional metal seeding can influence electron and phonon transport, and the electronic band structure in the nanomaterials. Here, we review recent advances in the growth and application of self-seeded Ge and Ge-based binary alloy (GeSn) nanowires. Different fabrication methods for growing self-seeded Ge nanowires are delineated and correlated with metal seeded growth. This review also highlights the requirement and advantage of self-seeded growth approach for Ge nanomaterials in the potential applications in energy storage and nanoelectronic devices.

Mechanistic Insights into Promoted Hydrolysis of Phosphoester Bonds by MoO2Cl2(DMF)2.

A phosphoester bond is a crucial structural block in biological systems, whose occurrence is regulated by phosphatases. Molybdenum compounds have been reported to be active in phosphate ester hydrolysis of model phosphates. Specifically, MoO2Cl2(DMF)2 is active in the hydrolysis of para-nitrophenyl phosphate (pNPP), leading to heteropolyoxometalate structures. We use density functional theory (DFT) to clarify the mechanism by which these species promote the hydrolysis of the phosphoester bond. The present calculations give insight into several key aspects of this reaction: (i) the speciation of this complex prior to interaction with the phosphate (DMF release, Mo-Cl hydrolysis, and pH influence on the speciation), (ii) the competition between phosphate addition and the molybdate nucleation process, (iii) and the mechanisms by which some plausible active species promote this hydrolysis in different conditions. We described thoroughly two different pathways depending on the nucleation possibilities of the molybdenum complex: one mononuclear mechanism, which is preferred in conditions in which very low complex concentrations are used, and another dinuclear mechanism, which is preferred at higher concentrations.

Probing the Catalytically Active Species in POM-Catalysed DNA-Model Hydrolysis*.

Phosphoester hydrolysis is an important chemical step in DNA repair. One archetypal molecular model of phosphoesters is para-nitrophenylphosphate (pNPP). It has been shown previously that the presence of molecular metal oxide [Mo7 O24 ]6- may catalyse the hydrolysis of pNPP through the partial decomposition of polyoxomolybdate framework resulting in a [(PO4 )2 Mo5 O15 ]6- product. Real-time monitoring of the catalytic system using electrospray ionisation mass spectrometry (ESI-MS) provided a glance into the species present in the reaction mixture and identification of potential catalytic candidates. Following up on the obtained spectrometric data, Density Functional Theory (DFT) calculations were carried out to characterise the hypothetical intermediate [Mo5 O15 (pNPP)2 (H2 O)6 ]6- that would be required to form under the hypothesised transformation. Surprisingly, our results point to the dimeric [Mo2 O8 ]4- anion resulting from the decomposition of [Mo7 O24 ]6- as the active catalytic species involved in the hydrolysis of pNPP rather than the originally assumed {Mo5 O15 } species. A similar study was carried out involving the same species but substituting Mo by W. The mechanism involving W species showed a higher barrier and less stable products in agreement with the non-catalytic effect found in experimental results.

Electron-Transfer-Induced Side-Chain Cleavage in Tryptophan Facilitated through Potassium-Induced Transition-State Stabilization in the Gas Phase.

Fragmentation of transient negative ions of tryptophan molecules formed through electron transfer in collisions with potassium atoms is presented for the first time in the laboratory collision energy range of 20 up to 100 eV. In the unimolecular decomposition process, the dominating side-chain fragmentation channel is assigned to the dehydrogenated indoline anion, in contrast to dissociative electron attachment of free low-energy electrons to tryptophan. The role of the collision complex formed by the potassium cation and tryptophan negative ion in the electron transfer process is significant for the mechanisms that operate at lower collision energies. At those collision times, on the order of a few tens of fs, the collision complex may not only influence the lifetime of the anion but also stabilize specific transition states and thus alter the fragmentation patterns considerably. DFT calculations, at the BHandHLYP/6-311++G(3df,2pd) level of theory, are used to explore potential reaction pathways and the evolvement of the charge distribution along those.

Learning to Model G-Quadruplexes: Current Methods and Perspectives.

G-quadruplexes have raised considerable interest during the past years for the development of therapies against cancer. These noncanonical structures of DNA may be found in telomeres and/or oncogene promoters, and it has been observed that the stabilization of such G-quadruplexes may disturb tumor cell growth. Nevertheless, the mechanisms leading to folding and stabilization of these G-quadruplexes are still not well established, and they are the focus of much current work in this field. In seminal works, stabilization was observed to be produced by cations. However, subsequent studies showed that different kinds of small molecules, from planar and nonplanar organic molecules to square-planar and octahedral metal complexes, may also lead to the stabilization of G-quadruplexes. Thus, the comprehension and rationalization of the interaction of these small molecules with G-quadruplexes are also important topics of current interest in medical applications. To shed light on the questions arising from the literature on the formation of G-quadruplexes, their stabilization, and their interaction with small molecules, synergies between experimental studies and computational works are needed. In this review, we mainly focus on in silico approaches and provide a broad compilation of different leading studies carried out to date by different computational methods. We divide these methods into twomain categories: (a) classical methods, which allow for long-timescale molecular dynamics simulations and the corresponding analysis of dynamical information, and (b) quantum methods (semiempirical, quantum mechanics/molecular mechanics, and density functional theory methods), which allow for the explicit simulation of the electronic structure of the system but, in general, are not capable of being used in long-timescale molecular dynamics simulations and, therefore, give a more static picture of the relevant processes.

Photocatalytic degradation of acetaminophen and caffeine using magnetite-hematite combined nanoparticles: kinetics and mechanisms.

The increased use of pharmaceutical and personal care products (PPCPs) has contributed to the contamination of water systems and put pressure on the development of new techniques to deal with this problem. Acetaminophen (paracetamol), a common analgesic and antipyretic drug, and caffeine, a known central nervous system stimulant, are being used frequently by many people and found in large amounts in wastewater systems. In this work, their removal, by photocatalytic degradation, was promoted using magnetic nanoparticles (NPs) based on iron oxides. Besides being obtained from cheap and plentiful source, the magnetic properties of these NPs provide an easy way to separate them from the solution when the reaction is complete. Three types of hematite-based NPs, one pure (1) and two of them composed by a magnetite core partially (2) or completely (3) covered by a hematite shell, were synthesized and characterized. Sample 2 was the best photocatalyst for both pollutants' photo-assisted degradation. Under UV-vis irradiation and using a 0.13 g catalyst/L solution, the total acetaminophen and caffeine degradation (20 ppm/150 mL) was achieved in 45 min and 60 min, respectively. The identification of some of the intermediate products was carried out by liquid chromatography in combination with electrospray ionization mass spectrometry. A complementary Density Functional Theory (DFT) study revealed the relative stability of several species formed during the acetaminophen and caffeine degradation processes and gave some insight about the most favorable degradation pathways.

Elucidating the intercalation of methylated 1,10-phenanthroline with DNA: the important weight of the CH/H interactions and the selectivity of CH/π and CH/n interactions.

Flat molecules like phenanthroline derivatives intercalate between base pairs of deoxyribonucleic acid and produce cytotoxic effects against tumoral cells. Elucidating the way of intercalation and its modulation on their efficiency by substitution still remains a challenging topic of research. In this work we analysed the intercalation via the major groove of methylated derivatives of phenanthroline, in different number and position, between guanine-cytosine base pairs. We studied our systems by using semi-empirical methods and density functional theory including dispersion corrections with the PM6-DH2 Hamiltonian and the B3LYP-D3 functional. We explored the geometry and electronic structure by means of the quantum theory of atoms in molecules and non-covalent interactions index analyses, whereas the interaction energy was estimated by means of two different approaches: one taking into account the results from the quantum theory of atoms in molecules analysis and the other based on the so-called energy decomposition analysis. The effect of solvation was also taken into consideration. Our studies show that CH/π and CH/n interactions by means of the -CH3 groups of methylated phen follow a clear pattern for any number of -CH3 groups and their position in the methylated phen ligand. That is, they try to produce the CH/π and CH/n interactions with the O and N heteroatoms of the base pairs and with the O atoms of the sugar and phosphate backbone. These findings suggest that the modulation of the intercalation of ligands that are able to form CH/π and CH/n weak interactions with the deoxyribonucleic acid is ruled not only by the number and position of the substitutions of the ligands but also by some key sites, which are the O and N atoms of the deoxyribonucleic acid in our analysed systems. It suggests some key and lock mechanism in which the interacting fragments fit like puzzle pieces in order to achieve the optimal interaction for the stabilization of the system. Interaction energies were calculated by using different approaches which converged to similar trends about the number and position of the -CH3 groups. The important weight of the CH/H interactions in the total interaction energy must be highlighted.

Computational Studies on the Binding Preferences of Molybdenum(II) Phenanthroline Complexes with Duplex DNA. The Important Role of the Ancillary Ligands.

The interaction of two isomers, equatorial (Eq) and axial (Ax), of the [Mo(η3-C3H5)Br(CO)2(phen)] metal complex with DNA was studied by using large-scaling density functional theory methods including dispersion for the whole system, represented as a d(AGACGTCT)2 DNA octamer, to gain insight into its experimentally found cytotoxicity. Three different modes of interaction were considered: (1) minor groove (mg) binding, (2) intercalation through the major groove (MG), and (3) the apparently unexpected intercalation via the mg. Computed formation energies, energy decomposition analysis, solvation energies, and noncovalent interaction analysis explain the preference for Eq and Ax isomers of the complex for intercalation via the mg. π-π interactions of the phenanthroline (phen) flat ligand that appear in the intercalation mode and do not exist for the mg binding mode suggest the preference of [Mo(η3-C3H5)Br(CO)2(phen)] for intercalation. On the other hand, the role of the ancillary ligands is crucial for better interaction of the metal complex including phen than when the phen ligand alone is considered because of their additional interactions with base pairs (bps). The role of the ancillary ligands is enhanced when intercalation takes place through the mg because such ligands are able to interact not only with bps but also with the sugar and phosphate backbone, whereas for intercalation through the MG, the interaction of these ligands is only with bps. This feature explains the preference of [Mo(η3-C3H5)Br(CO)2(phen)] for intercalation via the mg in crystal structures. Finally, the solvation penalty is more important for intercalation through the mg than via the MG, which suggests a subtle mechanism involving weak interactions with solvent molecules to explain the selectivity for intercalation in solution to answer the MG versus mg question.

Unraveling the Modulation of the Activity in Drugs Based on Methylated Phenanthroline When Intercalating between DNA Base Pairs.

Phenanthroline derivatives intercalate between base pairs of DNA and produce cytotoxic effects against tumoral cells. Nevertheless, modulation of their efficiency by substitution remains unclear in bibliography. In this work, the effects of methylation of phenanthroline, in number and position, when it intercalates between guanine-cytosine base pairs (GC/CG), were studied with PM6-DH2 and DFT-D methods including dispersion corrections. An analysis of the geometries, electronic structure, and energetics in the interaction was carried out for the studied systems. Our results were compared to experimental works to gain insight on the relation structure-interaction for the intercalated system with cytotoxicity. The trends are explained including not only intrinsic contributions to energy, ΔEPauli, ΔEdisp, ΔEorb, and ΔEelstat, but also the solvation energy, ΔESolv. A subtle balance between the number of stabilizing weak interactions (CH/π, CH/n, etc.) and steric hindrance seems to be related to the efficiency of such drugs.

Development of anisamide-targeted PEGylated gold nanorods to deliver epirubicin for chemo-photothermal therapy in tumor-bearing mice.

BACKGROUND: Gold nanorods (AuNRs), due to the optical and electronic properties namely the surface plasma resonance, have been developed to achieve the light-mediated photothermal therapy (PTT) for cancer. However, PTT alone may suffer from inefficient tumor killing. Recently, the combination of PTT and chemotherapy has been utilized to achieve synergistic anticancer effects. METHODS: In this study, AuNRs capped with hexadecyltrimethylammonium bromide (CTAB), poly(acrylic acid) (PAA), and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of negatively charged anisamide-targeted PEGylated AuNRs (namely Au-CTAB-PAA-PEG-AA) for the combination of PTT and chemotherapy (termed as chemo-photothermal therapy [CPTT]). Epirubicin (EPI, an anthracycline drug) was efficiently loaded onto the surface of Au800-CTAB-PAA-PEG-AA via the electrostatic interaction forming Au800-CTAB-PAA-PEG-AA.EPI complex. RESULTS: The resultant complex demonstrated pH-dependent drug release, facilitated nucleus trafficking of EPI, and induced antiproliferative effects in human prostate cancer PC-3 cells. When Au800-CTAB-PAA-PEG-AA.EPI complex was further stimulated with desired laser irradiation, the synergistic outcome was evident in PC-3 xenograft mice. CONCLUSION: These results demonstrate a promising strategy for clinical application of CPTT in cancer.