Machine Learning-Based Prediction of Reduction Potentials for PtIV Complexes.

Some of the well-known drawbacks of clinically approved PtII complexes can be overcome using six-coordinate PtIV complexes as inert prodrugs, which release the corresponding four-coordinate active PtII species upon reduction by cellular reducing agents. Therefore, the key factor of PtIV prodrug mechanism of action is their tendency to be reduced which, when the involved mechanism is of outer-sphere type, is measured by the value of the reduction potential. Machine learning (ML) models can be used to effectively capture intricate relationships within PtIV complex data, leading to highly accurate predictions of reduction potentials and other properties, and offering significant insights into their electrochemical behavior and potential applications. In this study, a machine learning-based approach for predicting the reduction potentials of PtIV complexes based on relevant molecular descriptors is presented. Leveraging a data set of experimentally determined reduction potentials and a diverse range of molecular descriptors, the proposed model demonstrates remarkable predictive accuracy (MSE = 0.016 V2, RMSE = 0.13 V, R2 = 0.92). Ab initio calculations and a set of different machine learning algorithms and feature engineering techniques have been employed to systematically explore the relationship between molecular structure and similarity and reduction potential. Specifically, it has been investigated whether the reduction potential of these compounds can be described by combining ML models across different combinations of constitutional, topological, and electronic molecular descriptors. Our results not only provide insights into the crucial factors influencing reduction potentials but also offer a rapid and effective tool for the rational design of PtIV complexes with tailored electrochemical properties for pharmaceutical applications. This approach has the potential to significantly expedite the development and screening of novel PtIV prodrug candidates. The analysis of principal components and key features extracted from the model highlights the significance of structural descriptors of the 2D Atom Pairs type and the lowest unoccupied molecular orbital energy. Specifically, with just 20 appropriately selected descriptors, a notable separation of complexes based on their reduction potential value is achieved.

Halogen atom effect on the photophysical properties of substituted aza-BODIPY derivatives.

The influence of halogen atom substitution (Br and I), in different amounts and positions in an aza-BODIPY skeleton, on the photophysical properties of some aza-BODIPY derivatives has been investigated by using density functional theory and its time-dependent extension. The heavy atom effect on excitation energies, singlet-triplet energy gaps and spin-orbit matrix elements has been considered. The maximum absorption within the therapeutic window has been confirmed for all the aza-BODIPY derivatives. The feasible intersystem spin crossing pathways for the population of the lowest triplet state, that will depend on the values of the spin-orbit matrix elements, the energy gap as well as the orbital composition of the involved states have been found to most likely involve the S1 and T1 or T2 states. The outcomes of computations support the potential therapeutic use of these compounds as photosensitizers in photodynamic therapy.

Mechanistic investigation of trimethylamine-N-oxide reduction catalysed by biomimetic molybdenum enzyme models.

In this paper, we report a theoretical investigation of the reduction reaction mechanism of Me3NO using molybdenum containing systems that are functional and structural analogues of trimethylamine N-oxide reductase mononuclear molybdenum enzyme. The reactivity of the monooxomolybdenum(IV) benzenedithiolato complex and its derivatives to carbamoyl (t-BuNHCO) and acylamino (t-BuCONH) substituents on the benzene rings in both cis and trans arrangements was explored. The calculated energy profiles describing the steps of two mechanisms of attack considered viable (named cis- and trans-attack) by the Me3NO substrate at cis and trans positions with respect to the oxo ligand show that the attack on cis is energetically more favourable than the attack on trans. Along the pathway for the cis-attack the first step of the reaction, that is rate-determining for all the studied compounds, is the approach of the substrate to the Mo centre in cis to the oxo ligand that causes a distortion of the initial square-pyramidal geometry of the complex. The reaction steps involved in the trans position attack were also explored. Calculations confirm that, as previously suggested, the introduction of ligands able to form intramolecular NH···S hydrogen bonds accelerates the reduction of the Me3NO substrate and contributes to the tuning of the reactivity of molybdoenzyme models.

LANL2DZ basis sets recontracted in the framework of density functional theory.

In this paper we report recontracted LANL2DZ basis sets for first-row transition metals. The valence-electron shell basis functions were recontracted using the PWP86 generalized gradient approximation functional and the hybrid B3LYP one. Starting from the original LANL2DZ basis sets a cyclic method was used in order to optimize variationally the contraction coefficients, while the contraction scheme was held fixed at the original one of the LANL2DZ basis functions. The performance of the recontracted basis sets was analyzed by direct comparison between calculated and experimental excitation and ionization energies. Results reported here compared with those obtained using the original basis sets show clearly an improvement in the reproduction of the corresponding experimental gaps.

Newly developed basis sets for density functional calculations.

Optimized contracted Gaussian basis sets of double-zeta valence polarized (DZVP) quality for first-row transition metals are presented. The DZVP functions were optimized using the PWP86 generalized gradient approximation (GGA) functional and the B3LYP hybrid functional. For a careful analysis of the basis sets performance the transition metal atoms and cations excitation energies were calculated and compared with the experimental ones. The calculated values were also compared with those obtained using the previously available DZVP basis sets developed at the local-density functional level. Because the new basis sets work better than the previous ones, possible reasons of this behavior are analyzed. The newly developed basis sets also provide a good estimation of other atomic properties such as ionization energies.

Síndrome de Meigs con valores elevados de CA 125. Aportación de un caso y revisión de la bibliografía / Meig´s syndrome with high levels of CA 125. A case report and literature

Se presenta un caso de síndrome de Meigs en una paciente de 59 años, provocado por un fibroma ovárico. La elevación del antígeno CA 125 y las imágenes ecográficas y de la tomografía axial computarizada hicieron sospechar la presencia de un proceso maligno (AU)

On the hardness evaluation in solvent for neutral and charged systems.

The influence of water on the hardness values of a series of neutral and charged molecules has been studied in the framework of density functional theory using the polarizable continuum model to take into account solvent effects. Three working formulas already widely tested in gas-phase have been used and the results compared. Two of the methods employed going from gas phase to solvent phase give values that do not change, while the results of the third method show remarkable changes. To check the reliability of the hardness behavior found, a test based on the hard-soft/acid-base principle and the calculation of the free energy of reaction has been applied using the adopted procedures.

Reaction of SC+(1D,3D) with H2O, NH3, and CH4: a density functional study.

Density Functional Theory has been used to explore quantitative details of the potential energy hypersurface for the insertion reaction of scandium ion into the O-H, N-H, and C-H bond of water, ammonia, and methane molecules leading to H2 elimination. Both singlet and triplet state channels have been considered. On the basis of the obtained results, it is possible to conclude that for the molecules considered the reaction is a spin-forbidden process. Indeed, it starts in the triplet ground state and ends in the singlet state, the change of the spin state probably occurring immediately after the formation of the electrostatic complex intermediate.

[Lingual hamartoma]. / Hamartoma lingual.

The hamartoma is a benign tumor resulting of a mixture of normal and mature tissues and cells, sitting on an organ or tissue showing identical cell components. From the perusal done of the bibliography they appear as rare malformations basically compound of fibrous tissue, fat, acini of salivary glands and smooth muscle.

[Chordoma of the base of the skull. A case report]. / Cordoma de base de craneo. A proposito de un caso.

Chordomas of the skull base are neoplasms derived from persistent embryologic remnants. In spite of its histologic classification as benign tumors, the site and the adverse possibilities of the management its behaviour is malignant like. The case here referred to was localized in the basioccipital region and protruded in the rhinopharynx. Perusal of the bibliography and prognostic assessment of these type of patients.