Are compliance constants ill-defined descriptors for weak interactions?

Just as the potential energy can be written as a quadratic form in internal coordinates, so it can also be expanded in terms of generalized forces. The resulting coefficients are termed compliance constants. In this article, the suitability of compliance constants as non-covalent bond strength descriptors is studied (a) for a series of weakly bound hydrogen halide–rare gas complexes applying a configuration interaction theory, (b) for a double stranded DNA 4-mer using approximate density functional methods and finally (c) for a double stranded DNA 20-mer using empirical force fields. Our results challenge earlier studies, which concluded the inappropriateness of compliance constants as soft matter descriptors. The discrepancy may be ascribed, inter alia, to the application of an oversimplified potential function in these earlier studies, assuming a central forces approximation

CT perfusion in patients with lung cancer: Squamous cell Carcinoma and Adenocarcinoma show a different Blood Flow

Objectives. To characterize tumour baseline blood flow (BF) in two lung cancer subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC), also investigating those \u201cborderline\u201d cases whose perfusion value is closer to the group mean of the other histotype. Materials and Methods. 26 patients (age range 36-81 years) with primary Non-Small Cell Lung Cancer (NSCLC), subdivided into 19 AC and 7 SCC, were enrolled in this study and underwent a CT perfusion, at diagnosis. BF values were computed according to the maximum-slope method and unreliable values (e.g., arising from artefacts or vessels) were automatically removed. The one-tail Welch\u2019s t-test (p-value < 0.05) was employed for statistical assessment. Results. At diagnosis, mean BF values (in [mL/min/100g]) of AC group [(83.5 \ub1 29.4)] are significantly greater than those of SCC subtype [(57.0 \ub1 27.2)] (p-value = 0.02). However, two central SCCs undergoing artefacts from vena cava and pulmonary artery have an artificially increased mean BF. Conclusions. The different hemodynamic behaviour of AC and SCC should be considered as a biomarker supporting treatment planning to select the patients, mainly with AC, that would most benefit from antiangiogenic therapies. The significance of results was achieved by automatically detecting and excluding artefactual BF values

Interaction of Cd(II) and Ni(II) terpyridine complexes with model polynucleotides: a multidisciplinary approach

Two metal complexes of 2,2′:6′,2″-terpyridine (terpy), i.e. Cd(terpy)Cl2 and Ni(terpy)Cl2·3H2O, have been prepared and extensively characterized. The interaction of Cd(terpy)Cl2 with synthetic DNA models, poly(dA-dT)·poly(dA-dT) (polyAT) and poly(dG-dC)·poly(dG-dC) (polyGC), has been studied by CD, fluorescence and UV-vis electronic absorption spectroscopy at several metal/polynucleotide-phosphate ratios and for different NaCl concentrations. All the experimental results indicate an intercalative mechanism of interaction. The optimized geometry of the cadmium complex intercalated between the sixth and seventh base pairs of (AT) and (GC) dodecanucleotide duplexes, obtained by quantum mechanics/molecular mechanics (QM/MM) calculations, lends support to the proposed mechanism. The calculated models provide some additional structural details of the intercalation complex at the molecular level. To evidence the influence of the charge and geometry of the metal complex on the mechanism of interaction with polynucleotides, the nickel complex-polyAT system has been studied to some extent by means of CD and UV-vis spectroscopy, and by thermal melting experiments. The results suggest that the octahedral complex cation [Ni(terpy)(H2O)2Cl]+ interacts with polyAT by partial intercalation assisted by electrostatic interaction with the negative charges of the backbone phosphate groups

(Dipyrido[3,2-a:2',3'-c]phenazine)(glycinato)copper(II) perchlorate: A novel DNA-intercalator with anti-proliferative activity against thyroid cancer cell lines

A novel copper(II) heteroleptic complex of dipyrido[3,2-a:2′,3′-c]phenazine (dppz) and glycinato (gly) as chelating ancillary ligand, [Cu(dppz)(gly)]ClO4 (1), was synthesized and characterized. X-ray crystallography revealed that the coordination geometry of the cationic [Cu(dppz)(gly)]+ unit is hexacoordinated and shows a distorted octahedral coordination geometry in the solid state, with the N,N and N,O chelating atoms of dppz and glycinato, respectively, in the square plane and in which the planar units are connected in a monodimensional polymeric array by the apical copper coordination of the second carboxylic oxygen atom. Biological assays showed that 1 exhibits a remarkable anti-proliferative activity against the two human anaplastic thyroid cancer cell lines 8505c (BrafV600E/V600E) and SW1736 (BrafWT/V600E), in a dose- and time-dependent manner. In details, the IC50 after 48 h of drug exposure was 2.86±0.54 μM for SW1736 and 1.05±0.48 μM for 8505c. On the other hand, the IC50 shown by cis-diamminedichloroplatinum(II) (cisplatin) against the same cell lines was 2.50±0.40 μM and 6.03±0.78 μM, respectively. Optical microscopy observations, after 48 h of treatment, showed morphological cell changes typical of apoptosis, confirmed by DNA ladder assays. DNA interaction studies, performed by UV absorption spectrophotometry, circular dichroism and viscosimetry, clearly showed that [Cu(dppz)(gly)]ClO4 is a DNA-intercalator, with a DNA-binding constant, Kb, of 2.1×106 M−1, suggesting that the mechanism of the cytotoxic activity can be related to its DNA-binding

The interaction of native DNA with iron(III)-N,N’-ethylene-bis(salicylideneiminato)-chloride

The interaction between native calf thymus deoxyribonucleic acid (DNA) and FeIII-N,N′-ethylene-bis (salicylideneiminato)- chloride, Fe(Salen)Cl, was investigated in aqueous solutions by UV-visible (UV-vis) absorption, circular dichroism (CD), thermal denaturation and viscosity measurements. The results obtained from CD, UV-vis and viscosity measurements exclude DNA intercalation and can be interpreted in terms of an electrostatic binding between the Fe(Salen)+ cation and the phosphate groups of DNA. The trend of the UV-vis absorption band of the Fe(Salen)Cl complex at different ratios [DNAphosphate]/[Fe(Salen)Cl] and the large increase of the melting temperature of DNA in the presence of Fe(Salen)Cl, support the hypothesis of an external electrostatic interaction between the negatively charged DNA double helix and the axially stacked positively charged Fe(Salen)+ moieties, analogously to what reported for a number of porphyrazines and metal-porphyrazine complexes interacting with DNA

The Primacy of High b-Value 3T-DWI Radiomics in the Prediction of Clinically Significant Prostate Cancer

Predicting clinically significant prostate cancer (csPCa) is crucial in PCa management. 3T-magnetic resonance (MR) systems may have a novel role in quantitative imaging and early csPCa prediction, accordingly. In this study, we develop a radiomic model for predicting csPCa based solely on native b2000 diffusion weighted imaging (DWIb2000) and debate the effectiveness of apparent diffusion coefficient (ADC) in the same task. In total, 105 patients were retrospectively enrolled between January–November 2020, with confirmed csPCa or ncsPCa based on biopsy. DWIb2000 and ADC images acquired with a 3T-MRI were analyzed by computing 84 local first-order radiomic features (RFs). Two predictive models were built based on DWIb2000 and ADC, separately. Relevant RFs were selected through LASSO, a support vector machine (SVM) classifier was trained using repeated 3-fold cross validation (CV) and validated on a holdout set. The SVM models rely on a single couple of uncorrelated RFs (ρ < 0.15) selected through Wilcoxon rank-sum test (p ≤ 0.05) with Holm–Bonferroni correction. On the holdout set, while the ADC model yielded AUC = 0.76 (95% CI, 0.63–0.96), the DWIb2000 model reached AUC = 0.84 (95% CI, 0.63–0.90), with specificity = 75%, sensitivity = 90%, and informedness = 0.65. This study establishes the primary role of 3T-DWIb2000 in PCa quantitative analyses, whilst ADC can remain the leading sequence for detection

The interaction of native DNA with Zn(II) and Cu(II) complexes of 5-triethyl ammonium methyl salicylidene orto-phenylendiimine

The interaction of native calf thymus DNA with the Zn(II) and Cu(II) complexes of 5-triethyl ammonium methyl salicylidene ortophenylendiimine (ZnL2+ and CuL2+), in 1 mM Tris-HCl aqueous solutions at neutral pH, has been monitored as a function of the metal complex-DNA molar ratio by UV absorption spectro photometry, circular dichroism (CD) and fluorescence spectroscopy. The results support for an intercalative interaction of both ZnL2+ and CuL2+ with DNA, showing CuL2+ an affinity of approximately 10 times higher than ZnL2+. In particular, the values of the binding constant, determined by UV spectrophotometric titration, equal to 7.3 x 10(4) and 1.3 x 10(6) M-1. for ZnL2+ and CuL2+, respectively, indicate the occurrence of a marked interaction with a binding size of about 0.7 in base pairs. The temperature dependence of the absorbance at 258 nm suggests that both complexes strongly increase the DNA melting temperature (Tm) already at metal complex-DNA molar ratios equal to 0.1. As evidenced by the quenching of the fluorescence of ethidium bromide-DNA solutions in the presence of increasing amounts of metal complex, ZnL2+ and CuL2+ are able to displace the ethidium cation intercalated into DNA. A tight ZnL2+-DNA and CuL2+-DNA binding has been also proven by the appearance, in both metal complex-DNA solutions, of a broad induced CD band in the range 350-450 nm. In the case of the CuL2+-DNA system, the shape of the CD spectrum, at high CuL2+ content, is similar to that observed for psi-DNA solutions. Such result allowed us to hypothesize that CuL2+ induces the formation of supramolecular aggregates of DNA in aqueous solutions