Impact of Conventional and Potential New Metal-Based Drugs on Lipid Metabolism in Osteosarcoma MG-63 Cells.

This work investigated the mechanisms of action of conventional drugs, cisplatin and oxaliplatin, and the potentially less deleterious drug Pd2Spermine (Spm) and its Pt(II) analog, against osteosarcoma MG-63 cells, using nuclear-magnetic-resonance metabolomics of the cellular lipidome. The Pt(II) chelates induced different responses, namely regarding polyunsaturated-fatty-acids (increased upon cisplatin), suggesting that cisplatin-treated cells have higher membrane fluidity/permeability, thus facilitating cell entry and justifying higher cytotoxicity. Both conventional drugs significantly increased triglyceride levels, while Pt2Spm maintained control levels; this may reflect enhanced apoptotic behavior for conventional drugs, but not for Pt2Spm. Compared to Pt2Spm, the more cytotoxic Pd2Spm (IC50 comparable to cisplatin) induced a distinct phospholipids profile, possibly reflecting enhanced de novo biosynthesis to modulate membrane fluidity and drug-accessibility to cells, similarly to cisplatin. However, Pd2Spm differed from cisplatin in that cells had equivalent (low) levels of triglycerides as Pt2Spm, suggesting the absence/low extent of apoptosis. Our results suggest that Pd2Spm acts on MG-63 cells mainly through adaptation of cell membrane fluidity, whereas cisplatin seems to couple a similar effect with typical signs of apoptosis. These results were discussed in articulation with reported polar metabolome adaptations, building on the insight of these drugs' mechanisms, and particularly of Pd2Spm as a possible cisplatin substitute.

Fluorinated Mn(III)/(II)-Porphyrin with Redox-Responsive 1 H and 19 F Relaxation Properties.

A new fluorinated manganese porphyrin, (Mn-TPP-p-CF3 ) is reported capable of providing, based on the Mn(III)/Mn(II) equilibrium, dual 1 H relaxivity and 19 F NMR response to redox changes. The physical-chemical characterization of both redox states in DMSO-d6 /H2 O evidenced that the 1 H relaxometric and 19 F NMR properties are appropriate for differential redox MRI detection. The Mn(III)-F distance (dMn-F =9.7-10 Å), as assessed by DFT calculations, is well tailored to allow for adequate paramagnetic effect of Mn(III) on 19 F T1 and T2 relaxation times. Mn-TPP-p-CF3 has a reversible Mn(II)/Mn(III) redox potential of 0.574 V vs. NHE in deoxygenated aqueous HEPES/ THF solution. The reduction of Mn(III)-TPP-p-CF3 in the presence of ascorbic acid is slowly, but fully reversed in the presence of air oxygen, as monitored by UV-Vis spectrometry and 19 F NMR. The broad 1 H and 19 F NMR signals of Mn(III)-TPP-p-CF3 disappear in the presence of 1 equivalent ascorbate replaced by a shifted and broadened 19 F NMR signal from Mn(II)-TPP-p-CF3 . Phantom 19 F MR images in DMSO show a MRI signal intensity decrease upon reduction of Mn(III)-TPP-p-CF3 , retrieved upon complete reoxidation in air within ~24 h. 1 H NMRD curves of the Mn(III)/(II)-TPP-p-CF3 chelates in mixed DMSO/water solvent have the typical shape of Mn(II)/Mn(III) porphyrins.

Breast cancer or surrounding normal tissue? A successful discrimination by FTIR or Raman microspectroscopy.

Breast cancer is a type of cancer with the highest incidence worldwide in 2021, with early diagnosis and rapid treatment intervention being the reasons for the decreasing mortality rate associated with the disease. The major challenge faced by clinicians and pathologists is the lack of accuracy in the histopathological analysis of biopsy or resection samples, leading to classification misdiagnosis and compromising the prognosis of patients. Spectral histopathology has provided great advances regarding cancer diagnosis, especially through the use of FTIR spectroscopy, proving to be a valuable complement to histopathological analyses. In this study unstained formalin-fixed paraffin embedded breast cancer tissue samples, collected from patients undergoing surgery and mounted on glass slides, were probed through FTIR and Raman microspectrocopy. Two classification models were constructed using the AdaBoost algorithm, both achieving >90% accuracy and successfully discriminating invasive breast carcinoma from surrounding normal tissue. Chemical maps from the interfaces of invasive breast carcinoma-surrounding normal tissue were also generated. This study showed the potential of spectral histopathology, in particular FTIR, for daily use in pathology laboratories, introducing few disruptions to the routine workflow while increasing the sensitivity, specificity and accuracy of the diagnoses.

Pd2Spermine Complex Shows Cancer Selectivity and Efficacy to Inhibit Growth of Triple-Negative Breast Tumors in Mice.

Pd2Spm is a dinuclear palladium(II)-spermine chelate with promising anticancer properties against triple-negative breast cancer (TNBC), a breast carcinoma subset with poor prognosis and limited treatment options. The present study evaluated the in vitro and in vivo anticancer effects of Pd2Spm compared to the reference metal-based drug cisplatin. Triple-negative breast cancer MDA-MB-231 cells, non-cancerous MCF-12A breast cells and chorioallantoic membrane (CAM) assay were used for antiproliferative, antimigratory and antiangiogenic studies. For an in vivo efficacy study, female CBA nude mice with subcutaneously implanted MDA-MB-231 breast tumors were treated with Pd2Spm (5 mg/kg/day) or cisplatin (2 mg/kg/day) administered intraperitoneally during 5 consecutive days. Promising selective antiproliferative activity of Pd2Spm was observed in MDA-MB-231 cells (IC50 values of 7.3-8.3 µM), with at least 10-fold lower activity in MCF-12A cells (IC50 values of 89.5-228.9 µM). Pd2Spm inhibited the migration of MDA-MB-231 cells, suppressed angiogenesis in CAM and decreased VEGF secretion from MDA-MB-231 cells with similar potency as cisplatin. Pd2Spm-treated mice showed a significant reduction in tumor growth progression, and tumors evidenced a reduction in the Ki-67 proliferation index and number of mitotic figures, as well as increased DNA damage, similar to cisplatin-treated animals. Encouragingly, systemic toxicity (hematotoxicity and weight loss) observed in cisplatin-treated animals was not observed in Pd2Spm-treated mice. The present study reports, for the first time, promising cancer selectivity, in vivo antitumor activity towards TNBC and a low systemic toxicity of Pd2Spm. Thus, this agent may be viewed as a promising Pd(II) drug candidate for the treatment of this type of low-prognosis neoplasia.

Who's Who? Discrimination of Human Breast Cancer Cell Lines by Raman and FTIR Microspectroscopy.

(1) Breast cancer is presently the leading cause of death in women worldwide. This study aims at identifying molecular biomarkers of cancer in human breast cancer cells, in order to differentiate highly aggressive triple-negative from non-triple-negative cancers, as well as distinct triple-negative subtypes, which is currently an unmet clinical need paramount for an improved patient care. (2) Raman and FTIR (Fourier transform infrared) microspectroscopy state-of-the-art techniques were applied, as highly sensitive, specific and non-invasive methods for probing heterogeneous biological samples such as human cells. (3) Particular biochemical features of malignancy were unveiled based on the cells' vibrational signature, upon principal component analysis of the data. This enabled discrimination between TNBC (triple-negative breast cancer) and non-TNBC, TNBC MSL (mesenchymal stem cell-like) and TNBC BL1 (basal-like 1) and TNBC BL1 highly metastatic and low-metastatic cell lines. This specific differentiation between distinct TNBC subtypes-mesenchymal from basal-like, and basal-like 1 with high-metastatic potential from basal-like 1 with low-metastatic potential-is a pioneer result, of potential high impact in cancer diagnosis and treatment.

A New Look into Cancer-A Review on the Contribution of Vibrational Spectroscopy on Early Diagnosis and Surgery Guidance.

In 2020, approximately 10 million people died of cancer, rendering this disease the second leading cause of death worldwide. Detecting cancer in its early stages is paramount for patients' prognosis and survival. Hence, the scientific and medical communities are engaged in improving both therapeutic strategies and diagnostic methodologies, beyond prevention. Optical vibrational spectroscopy has been shown to be an ideal diagnostic method for early cancer diagnosis and surgical margins assessment, as a complement to histopathological analysis. Being highly sensitive, non-invasive and capable of real-time molecular imaging, Raman and Fourier transform infrared (FTIR) spectroscopies give information on the biochemical profile of the tissue under analysis, detecting the metabolic differences between healthy and cancerous portions of the same sample. This constitutes tremendous progress in the field, since the cancer-prompted morphological alterations often occur after the biochemical imbalances in the oncogenic process. Therefore, the early cancer-associated metabolic changes are unnoticed by the histopathologist. Additionally, Raman and FTIR spectroscopies significantly reduce the subjectivity linked to cancer diagnosis. This review focuses on breast and head and neck cancers, their clinical needs and the progress made to date using vibrational spectroscopy as a diagnostic technique prior to surgical intervention and intraoperative margin assessment.

Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs.

This paper reports the first metabolomics study of the impact of new chelates Pt2Spm and Pd2Spm (Spm = Spermine) on human osteosarcoma cellular metabolism, compared to the conventional platinum drugs cisplatin and oxaliplatin, in order to investigate the effects of different metal centers and ligands. Nuclear Magnetic Resonance metabolomics was used to identify meaningful metabolite variations in polar cell extracts collected during exposure to each of the four chelates. Cisplatin and oxaliplatin induced similar metabolic fingerprints of changing metabolite levels (affecting many amino acids, organic acids, nucleotides, choline compounds and other compounds), thus suggesting similar mechanisms of action. For these platinum drugs, a consistent uptake of amino acids is noted, along with an increase in nucleotides and derivatives, namely involved in glycosylation pathways. The Spm chelates elicit a markedly distinct metabolic signature, where inverse features are observed particularly for amino acids and nucleotides. Furthermore, Pd2Spm prompts a weaker response from osteosarcoma cells as compared to its platinum analogue, which is interesting as the palladium chelate exhibits higher cytotoxicity. Putative suggestions are discussed as to the affected cellular pathways and the origins of the distinct responses. This work demonstrates the value of untargeted metabolomics in measuring the response of cancer cells to either conventional or potential new drugs, seeking further understanding (or possible markers) of drug performance at the molecular level.

Looking for Minor Phenolic Compounds in Extra Virgin Olive Oils Using Neutron and Raman Spectroscopies.

Extra virgin olive oil (EVOO) is defined as a functional food as it contains numerous phenolic components with well-recognized health-beneficial properties, such as high antioxidant and anti-inflammatory capacity. These characteristics depend on their structural/conformational behavior, which is largely determined by intra- and intermolecular H-bond interactions. While the vibrational dynamics of isolated compounds have been studied in a number of recent investigations, their signal in a real-life sample of EVOO is overwhelmed by the major constituent acids. Here, we provide a full characterization of the vibrational spectroscopic signal from commercially available EVOO samples using Inelastic Neutron Scattering (INS) and Raman spectroscopies. The spectra are dominated by CH2 vibrations, especially at about 750 cm-1 and 1300 cm-1. By comparison with the spectra from hydroxytyrosol and other minor phenolic compounds, we show that the best regions in which to look for the structure-activity information related to the minor polar compounds is at 675 and 1200 cm-1 for hydroxytyrosol, and around 450 cm-1 for all minor polar compounds used as reference, especially if a selectively deuterated sample is available. The regional origin of the EVOO samples investigated appears to be related to the different amount of phenolic esters versus acids as reflected by the relative intensities of the peaks at 1655 and 1747 cm-1.

Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in Mice.

Palladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistribution of a dinuclear palladium(II)-spermine chelate (Pd2Spm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinetic profiles of palladium/platinum in serum, serum ultrafiltrate and tissues (kidney, liver, brain, heart, lungs, ovaries, adipose tissue and mammary glands) were studied in healthy female Balb/c mice after a single intraperitoneal bolus injection of Pd2Spm (3 mg/kg bw) or cisplatin (3.5 mg/kg bw) between 0.5 and 48 h post-injection. Palladium in serum exhibited biphasic kinetics with a terminal half-life of 20.7 h, while the free palladium in serum ultrafiltrate showed a higher terminal half-life than platinum (35.5 versus 31.5 h). Palladium was distributed throughout most of the tissues except for the brain, with the highest values in the kidney, followed by the liver, lungs, ovaries, adipose tissue and mammary glands. The in vitro cellular accumulation was also evaluated in breast cancer cells, evidencing a passive diffusion as a mechanism of Pd2Spm's cellular entry. This study reports, for the first time, the favorable pharmacokinetics and biodistribution of Pd2Spm, which may become a promising pharmacological agent for cancer treatment.

Chemosteometric regression models of heat exposed human bones to determine their pre-burnt metric dimensions.

OBJECTIVES: Heat exposure can lead to apparently random osteometric changes that hinder the application of metric methods used for biological profiling. The impracticality of using objective and burn-specific osteometric methods reduces the chances of establishing the biological profiles of unknown individuals based on their skeletal remains. We investigated the potential of chemometry analysis based on infrared spectroscopy to predict the amount of heat-induced osteometric changes and how this reflected into sex estimation. MATERIAL AND METHODS: Bones from 41 identified adult skeletons (24 females and 17 males with ages between 62 and 90 years old) were experimentally burnt to maximum temperatures ranging from 450°C to 1,100°C (attained after 65 to 240 min). Measurements were taken both before and after each experiment and powder samples were analyzed through FTIR-ATR. Correlations among heat-induced metric changes and chemometric indices (crystallinity index; B-type carbonates; carbonate [A + B] to carbonate B ratio; hydroxyl to phosphate ratio; 630 cm-1 , 1450 cm-1 , 3572 cm-1 , and 3642 cm-1 ) were tested. Significant variables were used to build regression models to predict heat-induced metric change which were then tested on an independent set of samples. Agreement in sex estimation between the pre- and post-burnt samples was also evaluated. RESULTS: All indices were significantly correlated to heat-induced metric changes (α = .01) and the highest correlations were obtained for the 630 cm-1 , 3572 cm-1 , and crystallinity index. We confirmed that regression models based on chemometrics obtained from infrared spectra through FTIR-ATR are better at estimating heat-induced metric changes affecting bone and at sexing remains than other osteometric methods such as those based on correction factors or on metric references specific to calcined bones. DISCUSSION: Regression models avoid the subjectivity associated with the application of other methods. While the latter can be applied only to calcined bones, which is difficult to assess sometimes, regression models can be applied to all bones regardless of their condition. Also, regression models have the advantage of allowing to infer about heat-induced metric change on a case-by-case basis.

Surface Enhanced Raman Spectroscopy for Quantitative Analysis: Results of a Large-Scale European Multi-Instrument Interlaboratory Study.

Surface-enhanced Raman scattering (SERS) is a powerful and sensitive technique for the detection of fingerprint signals of molecules and for the investigation of a series of surface chemical reactions. Many studies introduced quantitative applications of SERS in various fields, and several SERS methods have been implemented for each specific application, ranging in performance characteristics, analytes used, instruments, and analytical matrices. In general, very few methods have been validated according to international guidelines. As a consequence, the application of SERS in highly regulated environments is still considered risky, and the perception of a poorly reproducible and insufficiently robust analytical technique has persistently retarded its routine implementation. Collaborative trials are a type of interlaboratory study (ILS) frequently performed to ascertain the quality of a single analytical method. The idea of an ILS of quantification with SERS arose within the framework of Working Group 1 (WG1) of the EU COST Action BM1401 Raman4Clinics in an effort to overcome the problematic perception of quantitative SERS methods. Here, we report the first interlaboratory SERS study ever conducted, involving 15 laboratories and 44 researchers. In this study, we tried to define a methodology to assess the reproducibility and trueness of a quantitative SERS method and to compare different methods. In our opinion, this is a first important step toward a "standardization" process of SERS protocols, not proposed by a single laboratory but by a larger community.

Anticancer activity of palladium-based complexes against triple-negative breast cancer.

Treatment of triple-negative breast carcinoma (TNBC) remains an unmet medical need with no targeted therapy available to date. Accounting for 10-30% of all human breast cancer tumors, this mammary carcinoma subtype has a particularly poor prognosis owing to its high metastatic potential, aggressive biology and limited pharmacological treatment options. Platinum chemotherapeutics are the mainstay therapy in patients with TNBC but their clinical use is limited by severe toxicity and acquired resistance. Palladium-based complexes are appealing alternative metal-based drugs because of significant similarities regarding structure and coordination chemistry with the platinum agents. This review summarizes the knowledge gathered so far on 121 Pd(II) complexes, emphasizing their anticancer activity and putative pharmacological targets toward TNBC.

Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent.

The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with spermine (Pd2Spm); ii) the anti-proliferative activity of Pd2Spm against a triple negative human breast carcinoma (MDA-MB-231); and finally iii) the putative interaction mediated by combination of Pd2Spm with Docetaxel. Anti-invasive (anti-angiogenic and anti-migratory) as well as anti-proliferative capacities were assessed, for different combination schemes and drug exposure times, using the CAM assay and VEGFR2 activity measurement, the MatrigelTM method and the SRB proliferation test. The results thus obtained evidence the ability of Pd2Spm to restrict angiogenesis and cell migration: Pd2Spm induced a marked inhibition of migration (43.8±12.2%), and a higher inhibition of angiogenesis (81.8±4.4% for total length values, at 4 µM) as compared to DTX at the clinical dosage 4x10-2 µM (26.4±14.4%; n = 4 to 11). Combination of Pd2Spm/DTX was more effective as anti-invasive and anti-proliferative than DTX or Pd2Spm in sole administration, which is compatible with the occurrence of synergism: for the anti-angiogenic effect, IC50(Pd2Spm/DTX) = 0.5/0.5x10-2 µM vs IC50(DTX) = 1.7x10-2 µM and IC50(Pd2Spm) = 1.6 µM. In conclusion, the reported effects of Pd2Spm on angiogenesis, migration and proliferation showed that this compound is a promising therapeutic agent against this type of breast cancer. Moreover, combined administration of Pd2Spm and DTX was found to trigger a substantial synergetic effect regarding angiogenesis inhibition as well as anti-migratory and anti-proliferative activities reinforcing the putative use of Pd(II) complexes in chemotherapeutic regimens. This is a significant outcome, aiming at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials.

Increased breast cancer cell toxicity by palladination of the polyamine analogue N (1),N (11)-bis(ethyl)norspermine.

Breast cancer is one of the most common malignant tumor forms among women and many women succumb to their disease. Thus, new anticancer agents that can efficiently improve patient survival are of the utmost importance. In this study, the effects of the polyamine analogues N (1),N (11)-bis(ethyl)norspermine (BENSpm) and N (1)-cyclo-propylmethyl-N (11)-ethylnorspermine (CPENSpm) and the synthesized dinuclear complexes Pd2BENSpm (Pd-BENSpm), Pt2CPENSpm (Pt-CPENSpm) and Pd2Spm (Pd-Spm) were investigated in normal-like breast epithelial MCF-10A cells and the breast cancer cell lines JIMT-1 and L56BR-C1. The overall data show that palladination of BENSpm resulted in enhanced cytotoxicity, in contrast to platination of CPENSpm that reduced cytotoxicity, which might be explained by differences in the cellular uptake of Pd-BENSpm and Pt-CPENSpm. BENSpm and Pd-BENSpm treatment reduced the CD44(+)CD24(-) putative cancer stem cell population, evaluated by flow cytometry. Furthermore, Pd-BENSpm was the most efficient compound regarding induction of DNA damage and decrease in colony formation in soft agar. Pt-CPENSpm and Pd-Spm, on the other hand, were shown to be the least toxic compounds of all tested. Pd-Spm efficiently reduced the cellular glutathione levels, which probably was a consequence of its metabolic inactivation by conjugation to this endogenous thiol. The normal-like cells were found to be less sensitive to the agents than the breast cancer cells. Our findings show that Pd-BENSpm exhibits promising anticancer effects which render it suitable for further optimization to develop a new metal-based chemotherapeutic drug for breast cancer treatment.

Lipophilic caffeic and ferulic acid derivatives presenting cytotoxicity against human breast cancer cells.

In the present work, lipophilic caffeic and ferulic acid derivatives were synthesized, and their cytotoxicity on cultured breast cancer cells was compared. A total of six compounds were initially evaluated: caffeic acid (CA), hexyl caffeate (HC), caffeoylhexylamide (HCA), ferulic acid (FA), hexyl ferulate (HF), and feruloylhexylamide (HFA). Cell proliferation, cell cycle progression, and apoptotic signaling were investigated in three human breast cancer cell lines, including estrogen-sensitive (MCF-7) and insensitive (MDA-MB-231 and HS578T). Furthermore, direct mitochondrial effects of parent and modified compounds were investigated by using isolated liver mitochondria. The results indicated that although the parent compounds presented no cytotoxicity, the new compounds inhibited cell proliferation and induced cell cycle alterations and cell death, with a predominant effect on MCF-7 cells. Interestingly, cell cycle data indicates that effects on nontumor BJ fibroblasts were predominantly cytostatic and not cytotoxic. The parent compounds and derivatives also promoted direct alterations on hepatic mitochondrial bioenergetics, although the most unexpected and never before reported one was that FA induces the mitochondrial permeability transition. The results show that the new caffeic and ferulic acid lipophilic derivatives show increased cytotoxicity toward human breast cancer cell lines, although the magnitude and type of effects appear to be dependent on the cell type. Mitochondrial data had no direct correspondence with effects on intact cells suggesting that this organelle may not be a critical component of the cellular effects observed. The data provide a rational approach to the design of effective cytotoxic lipophilic hydroxycinnamic derivatives that in the future could be profitably applied for chemopreventive and/or chemotherapeutic purposes.

Biologic activity of a dinuclear Pd(II)-spermine complex toward human breast cancer.

A dinuclear palladium-based complex (Pd(2) -Spm) was synthesized and compared with cisplatin (cDDP) on two different human breast cancer cell lines (MCF-7 and MDA-MB-231) as well as toward an untransformed cell line (BJ fibroblasts). The results obtained show that Pd(2) -Spm is more effective against the estrogen receptors [ER(-)] cell line MDA-MB-231, while cDDP displayed better results for the ER(+) MCF-7 cell line. It was shown that, like cDDP, Pd(2) -Spm triggers phosphorylation of H2AX, indicating that this compound damages DNA. Apart from DNA, Pd(2) -Spm also targets the cytoskeleton having a greater impact on cell morphology than cDDP. Pd(2) -Spm and cDDP have opposite antiproliferative activities in the presence of the PI3K inhibitor wortmannin. Furthermore, Pd(2) -Spm at an optimized concentration displays a rapid antiproliferative effect as opposed to cDDP, which seems to have a slower kinetics. The results point to a distinct mechanism of action for each of these complexes, which may explain their synergistic action when coadministrated.

Arcyriaflavin A monohydrate.

The asymmetric unit of the title compound comprises the monohydrated form of the natural product arcyriaflavin A [systematic name: 12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione monohydrate], C(20)H(11)N(3)O(2)·H(2)O. Individual molecular units are engaged in hydrogen-bonding interactions, forming two-dimensional zigzag supramolecular layers parallel to the (102) plane. The close packing of the layers is mediated by strong co-operative π-π stacking interactions, in tandem with interlayer hydrogen bonds involving the solvent water molecule.

Characterization of antioxidant olive oil biophenols by spectroscopic methods.

BACKGROUND: Olive oil contains numerous phenolic components with well-recognized health-beneficial activity. The major phenolic compounds present in olives and virgin olive oil-hydroxytyrosol, oleuropein and the oleuropein aglycones 3,4-DHPEA-EA and 3,4-DHPEA-EDA-as well as some of their metabolites were studied in the present work, regarding their main structural preferences. Vibrational spectroscopy (Raman) coupled to theoretical methods were used, aiming at fully characterizing the systems and therefore enabling their quick and reliable identification in food samples. RESULTS: The raman data, assisted by the theoretical simulations, allowed us to obtain the main geometrical and spectroscopic features of the olive oil constituents under study, which determine their known antioxidant and chemoprotective properties. In fact, it was verified that the spectra comprise distinctive bands for each compound, allowing their ready detection and differentiation. CONCLUSION: This is the first reported study on the structural behaviour of olive oil phenolic compounds, and it established Raman spectroscopy as a rapid, non-destructive and reliable analytical technique for identifying these bioactive components in dietary extracts. It can surpass other analytical methods currently used, once it allows the concomitant identification of several olive oil components in a particular sample.

Conformational and vibrational study of cis-diamminedichloropalladium(II).

A conformational and vibrational analysis of cis-diamminedichloropalladium(ii) (cDDPd) is reported. Several theoretical methods (from Hartree-Fock to Møller-Plesset and Density Functional Theory) combined with different all-electron basis-sets are evaluated, in view of determining the best suited strategy for accurately representing this molecule. This choice is based on the best compromise between accuracy and computational requirements. Different scaling models were tested for obtaining the best scaling schemes of the vibrational modes to be used in this type of inorganic systems. The structural parameters and vibrational results predicted by the calculations are compared with the corresponding experimental data, namely X-ray structure and vibrational spectra. Finally, a complete assignment of the cDDPd vibrational spectra is presented.

Use of effective core potential calculations for the conformational and vibrational study of platinum(II) anticancer drugs. cis-Diamminedichloroplatinum(II) as a case study.

In the light of the recognized anticancer properties of cisplatin-type inorganic systems, the exact knowledge of their conformational preferences is of the utmost importance for understanding their biological activity. The present study reports the use of theoretical (quantum mechanical) calculations for achieving this goal. An alternative calculation method to the use of the AE basis sets, both accurate and computationally feasible, was presently tested for the conformational and vibrational study of cis-diamminedichloroplatinum(II). Effective core potentials (ECPs) were used, within the HF methodology and, within the B3LYP and mPW1PW DFT protocols. The DFT methods (particularly mPW1PW) were found to be the best choice for describing cDDP (as compared to the HF methodology).