Tailoring chemical bonds to design unconventional glasses.

Glasses are commonly described as disordered counterparts of the corresponding crystals; both usually share the same short-range order, but glasses lack long-range order. Here, a quantification of chemical bonding in a series of glasses and their corresponding crystals is performed, employing two quantum-chemical bonding descriptors, the number of electrons transferred and shared between adjacent atoms. For popular glasses like SiO2, GeSe2, and GeSe, the quantum-chemical bonding descriptors of the glass and the corresponding crystal hardly differ. This explains why these glasses possess a similar short-range order as their crystals. Unconventional glasses, which differ significantly in their short-range order and optical properties from the corresponding crystals are only found in a distinct region of the map spanned by the two bonding descriptors. This region contains crystals of GeTe, Sb2Te3, and GeSb2Te4, which employ metavalent bonding. Hence, unconventional glasses are only obtained for solids, whose crystals employ theses peculiar bonds.

Carbonyl-Based Redox-Active Compounds as Organic Electrodes for Batteries: Escape from Middle-High Redox Potentials and Further Improvement?

Extracting─from the vast space of organic compounds─the best electrode candidates for achieving energy material breakthrough requires the identification of the microscopic causes and origins of various macroscopic features, including notably electrochemical and conduction properties. As a first guess of their capabilities, molecular DFT calculations and quantum theory of atoms in molecules (QTAIM)-derived indicators were applied to explore the family of pyrano[3,2-b]pyran-2,6-dione (PPD, i.e., A0) compounds, expanded to A0 fused with various kinds of rings (benzene, fluorinated benzene, thiophene, and merged thiophene/benzene). A glimpse of up-to-now elusive key incidences of introducing oxygen in vicinity to the carbonyl redox center within 6MRs─as embedded in the A0 core central unit common to all A-type compounds─has been gained. Furthermore, the main driving force toward achieving modulated low redox potential/band gaps thanks to fusing the aromatic rings for the A compound series was discovered.

Atomic Group Decomposition of Charge Transfer Excitation Global Indexes.

A model for decomposing the Le Bahers, Adamo, and Ciofini Charge Transfer (CT) Excitations global indexes ( J. Chem. Theory Comput. 2011, 7, 2498-2506) into molecular subdomains contributions is presented and a software, DOCTRINE (atomic group Decomposition Of the Charge TRansfer INdExes) for the implementation of this novel model has been coded. Although our method applies to any fuzzy or to any disjoint exhaustive partitioning of the real space, it is here applied using a definition of chemically relevant molecular subdomains based on the Atoms in Molecules Bader basins. This choice has the relevant advantage of associating intra or inter subdomain contributions to rigorously defined quantum objects, yet bearing a clear chemical meaning. Our method allows for a quantitative evaluation of the subdomain contributions to the charge transfer, the charge transfer excitation length and the dipole moment change upon excitation. All these global indexes may be obtained either from the electron density increment or the electron density depletion upon excitation. However, the subdomain contributions obtained from the two distributions generally differ, therefore allowing to distinguish whether the contribution to a given property of a given subdomain is dominated by one of the two distributions or if both are playing a significant role. As a toy system for the first application of our model, a typical [D-π-A, π = conjugated bridge] compound belonging to the merocyanine dyes family is selected, and the first four excited states of this compound in a strongly polar protic solvent and in a weakly polar solvent are thoroughly investigated.

Seeking for Optimal Excited States in Photoinduced Electron-Transfer Processes─The Case Study of Brooker's Merocyanine.

Material design enters an era in which control of electrons in atoms, molecules, and materials is an essential property to be predicted and thoroughly understood in view of discovering new compounds with properties optimized toward specific optical/optoelectronic applications. π-electronic delocalization and charge separation/recombination enter notably into the set of features that are highly desirable to tailor. Diverse domains are particularly relying on photoinduced electron-transfer (PET), including fields of paramount importance such as energy production through light-harvesting, efficient chemoreceptive sensors, or organic field-effect transistors. In view of completing the arsenal of strategies in this area, we selected Brooker's merocyanine─a typical [D-π-A] compound─as the case study and examined from time-dependent density functional theory the opportunity offered by selected excited states to reach a suited manipulation of the charge transfer (CT) extent. In addition to the consideration of diagnostic tools able to spot the charge amount (i.e., magnitude of electron fraction) transferred upon excitation (qCT), the spatial extent associated with such an electronic transition or CT length (DCT), as well as the corresponding variation in dipole moment between the ground and the excited states (µCT), further analysis of the excitation process was undertaken. The advantage of going beyond the above-mentioned molecular indicators─which can be considered as PET global indices─was explored on the basis of a partitioning of the electron density. Relevant insight was gained on the relation these global indices have with the evolution of (local) features characterizing either chemical bond or electron delocalization upon vertical excitations.

Prognostic Role of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma: A Large, Multicenter, Prospective Trial.

BACKGROUND: Circulating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC). MATERIALS AND METHODS: We designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression. RESULTS: One hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p = .002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16-3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p = .003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95-2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five. CONCLUSION: We provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC. IMPLICATIONS FOR PRACTICE: This prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.

Metal-Metal Bond in the Light of Pauling's Rules.

About 70 years ago, in the framework of his theory of chemical bonding, Pauling proposed an empirical correlation between the bond valences (or effective bond orders (BOs)) and the bond lengths. Till now, this simple correlation, basic in the bond valence model (BVM), is widely used in crystal chemistry, but it was considered irrelevant for metal-metal bonds. An extensive analysis of the quantum chemistry data computed in the last years confirms very well the validity of Pauling's correlation for both localized and delocalized interactions. This paper briefly summarizes advances in the application of the BVM for compounds with TM-TM bonds (TM = transition metal) and provides further convincing examples. In particular, the BVM model allows for very simple but precise calculations of the effective BOs of the TM-TM interactions. Based on the comparison between formal and effective BOs, we can easily describe steric and electrostatic effects. A possible influence of these effects on materials stability is discussed.

Redox Potential and Crystal Chemistry of Hexanuclear Cluster Compounds.

Most of TM6-cluster compounds (TM = transition metal) are soluble in polar solvents, in which the cluster units commonly remain intact, preserving the same atomic arrangement as in solids. Consequently, the redox potential is often used to characterize structural and electronic features of respective solids. Although a high lability and variety of ligands allow for tuning of redox potential and of the related spectroscopic properties in wide ranges, the mechanism of this tuning is still unclear. Crystal chemistry approach was applied for the first time to clarify this mechanism. It was shown that there are two factors affecting redox potential of a given metal couple: Lever's electrochemical parameters of the ligands and the effective ionic charge of TM, which in cluster compounds differs effectively from the formal value due to the bond strains around TM atoms. Calculations of the effective ionic charge of TMs were performed in the framework of bond valence model, which relates the valence of a bond to its length by simple Pauling relationship. It was also shown that due to the bond strains the charge depends mainly on the atomic size of the inner ligands.

Topology of the Electron Density and of Its Laplacian from Periodic LCAO Calculations on f-Electron Materials: The Case of Cesium Uranyl Chloride.

The chemistry of f-electrons in lanthanide and actinide materials is yet to be fully rationalized. Quantum-mechanical simulations can provide useful complementary insight to that obtained from experiments. The quantum theory of atoms in molecules and crystals (QTAIMAC), through thorough topological analysis of the electron density (often complemented by that of its Laplacian) constitutes a general and robust theoretical framework to analyze chemical bonding features from a computed wave function. Here, we present the extension of the Topond module (previously limited to work in terms of s-, p- and d-type basis functions only) of the Crystal program to f- and g-type basis functions within the linear combination of atomic orbitals (LCAO) approach. This allows for an effective QTAIMAC analysis of chemical bonding of lanthanide and actinide materials. The new implemented algorithms are applied to the analysis of the spatial distribution of the electron density and its Laplacian of the cesium uranyl chloride, Cs2UO2Cl4, crystal. Discrepancies between the present theoretical description of chemical bonding and that obtained from a previously reconstructed electron density by experimental X-ray diffraction are illustrated and discussed.

Enantioseparation of 5,5'-Dibromo-2,2'-Dichloro-3-Selanyl-4,4'-Bipyridines on Polysaccharide-Based Chiral Stationary Phases: Exploring Chalcogen Bonds in Liquid-Phase Chromatography.

The chalcogen bond (ChB) is a noncovalent interaction based on electrophilic features of regions of electron charge density depletion (σ-holes) located on bound atoms of group VI. The σ-holes of sulfur and heavy chalcogen atoms (Se, Te) (donors) can interact through their positive electrostatic potential (V) with nucleophilic partners such as lone pairs, π-clouds, and anions (acceptors). In the last few years, promising applications of ChBs in catalysis, crystal engineering, molecular biology, and supramolecular chemistry have been reported. Recently, we explored the high-performance liquid chromatography (HPLC) enantioseparation of fluorinated 3-arylthio-4,4'-bipyridines containing sulfur atoms as ChB donors. Following this study, herein we describe the comparative enantioseparation of three 5,5'-dibromo-2,2'-dichloro-3-selanyl-4,4'-bipyridines on polysaccharide-based chiral stationary phases (CSPs) aiming to understand function and potentialities of selenium σ-holes in the enantiodiscrimination process. The impact of the chalcogen substituent on enantioseparation was explored by using sulfur and non-chalcogen derivatives as reference substances for comparison. Our investigation also focused on the function of the perfluorinated aromatic ring as a π-hole donor recognition site. Thermodynamic quantities associated with the enantioseparation were derived from van't Hoff plots and local electron charge density of specific molecular regions of the interacting partners were inspected in terms of calculated V. On this basis, by correlating theoretical data and experimental results, the participation of ChBs and π-hole bonds in the enantiodiscrimination process was reasonably confirmed.

A revisit of the bond valence model makes it universal.

The use of simple, intuitive equations to correlate the geometry of crystal structures with electron descriptors of chemical bonds and material structural stability is a great advantage of the Bond Valence Model (BVM), which is based on Pauling's principles of bond order (BO) conservation and exponential BO/bond length relationship. However, the high potential of BVM to be used as an important analytical tool was overlooked in recent inorganic chemistry due to its empirical character and serious restrictions for its application. Recent quantum chemistry data (BOs and electron densities at the bond critical points, ρc) enable us to establish the validity of the BVM to any type of chemical bonds, as well as a direct BO/ρc relationship. Such a BVM revisit overcomes most of the limitations anticipated previously for the model and thus makes it universal. This Perspective highlights the advance in model development, in particular its application to compounds with metal-metal bonds, which allows us to establish (i) a linear correlation between BOs and stretching force constants used as a measure of the bond strength and (ii) a quantitative description of the steric/electrostatic effects in cluster compounds enabling us to understand their nature and the influence of such effects on structural stability. Thus, using interatomic distances, the simple Pauling equation and empirical constants, it is possible to calculate effective BOs and predict stretching force constants and electron densities at the bond critical points in any complex compound, all of this at zero cost!

A tool for deciphering the redox potential ranking of organic compounds: a case study of biomass-extracted quinones for sustainable energy.

Carbonyl compounds have emerged as promising organic electrodes for sustainable energy storage. Accelerating the process of performant materials discovery relies on the possibility of developing methodologies to enable scanning of various sets of candidates. The genesis of this educated guess strategy must be privileged to reduce the search space of experiments, accelerate this research area and contribute to sustainable effort. To address this challenge, we built a quantitative structure-activity relationship to unveil the origin of the redox potential magnitude as a function of both structural features and complexation effects. The potential of this prediction model was demonstrated on various ortho-quinones directly derived from naturally occurring catechols. In addition to the modulation provided by substituent changes, the possibility of applying various types of alkaline(-earth)-ion electrochemistry was examined thoroughly. The power of partitioning the total molecular energy into additive atomic group contributions is highlighted, and the construction of this robust strategy provides guidance towards rational selection of the most suitable compound/metal-ion couples. An upshift/downshift of the redox potential by switching from Li to Mg/Na is revealed, while the identification of the relative role played by the various components of the systems as well as electrostatic interactions is clearly identified. These results, particularly the evidence of the different substituent effects on the single/double reduction potentials and as a function of the type of electrochemistry (Li/Na/Mg), have important implications for designing new electroactive compounds with tailored redox properties.

Spin Density Topology.

Despite its role in spin density functional theory and it being the basic observable for describing and understanding magnetic phenomena, few studies have appeared on the electron spin density subtleties thus far. A systematic full topological analysis of this function is lacking, seemingly in contrast to the blossoming in the last 20 years of many studies on the topological features of other scalar fields of chemical interest. We aim to fill this gap by unveiling the kind of information hidden in the spin density distribution that only its topology can disclose. The significance of the spin density critical points, the 18 different ways in which they can be realized and the peculiar topological constraints on their number and kind, arising from the presence of positive and negative spin density regions, is addressed. The notion of molecular spin graphs, spin maxima (minima) joining paths, spin basins and of their valence is introduced. We show that two kinds of structures are associated with a spin-polarized molecule: the usual one, defined through the electron density gradient, and the magnetic structure, defined through the spin density gradient and composed in general by at least two independent spin graphs, related to spin density maxima and minima. Several descriptors, such as the spin polarization index, are introduced to characterize the properties of spin density critical points and basins. The study on the general features of the spin density topology is followed by the specific example of the water molecule in the 3B1 triplet state, using spin density distributions of increasing accuracy.

Factors Impacting σ- and π-Hole Regions as Revealed by the Electrostatic Potential and Its Source Function Reconstruction: The Case of 4,4'-Bipyridine Derivatives.

Positive electrostatic potential (V) values are often associated with σ- and π-holes, regions of lower electron density which can interact with electron-rich sites to form noncovalent interactions. Factors impacting σ- and π-holes may thus be monitored in terms of the shape and values of the resulting V. Further precious insights into such factors are obtained through a rigorous decomposition of the V values in atomic or atomic group contributions, a task here achieved by extending the Bader-Gatti source function (SF) for the electron density to V. In this article, this general methodology is applied to a series of 4,4'-bipyridine derivatives containing atoms from Groups VI (S, Se) and VII (Cl, Br), and the pentafluorophenyl group acting as a π-hole. As these molecules are characterized by a certain degree of conformational freedom due to the possibility of rotation around the two C-Ch bonds, from two to four conformational motifs could be identified for each structure through conformational search. On this basis, the impact of chemical and conformational features on σ- and π-hole regions could be systematically evaluated by computing the V values on electron density isosurfaces (VS) and by comparing and dissecting in atomic/atomic group contributions the VS maxima (VS,max) values calculated for different molecular patterns. The results of this study confirm that both chemical and conformational features may seriously impact σ- and π-hole regions and provide a clear analysis and a rationale of why and how this influence is realized. Hence, the proposed methodology might offer precious clues for designing changes in the σ- and π-hole regions, aimed at affecting their potential involvement in noncovalent interactions in a desired way.

From Diagnostic-Therapeutic Pathways to Real-World Data: A Multicenter Prospective Study on Upfront Treatment for EGFR-Positive Non-Small Cell Lung Cancer (MOST Study).

INTRODUCTION: Gefitinib, erlotinib, and afatinib represent the approved first-line options for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Because pivotal trials frequently lack external validity, real-world data may help to depict the diagnostic-therapeutic pathway and treatment outcome in clinical practice. METHODS: MOST is a multicenter observational study promoted by the Veneto Oncology Network, aiming at monitoring the diagnostic-therapeutic pathway of patients with nonsquamous EGFR-mutant NSCLC. We reported treatment outcome in terms of median time to treatment failure (mTTF) and assessed the impact of each agent on the expense of the regional health system, comparing it with a prediction based on the pivotal trials. RESULTS: An EGFR mutation test was performed in 447 enrolled patients, of whom 124 had EGFR mutation and who received gefitinib (n = 69, 55%), erlotinib (n = 33, 27%), or afatinib (n = 22, 18%) as first-line treatment. Because erlotinib was administered within a clinical trial to 15 patients, final analysis was limited to 109 patients. mTTF was 15.3 months, regardless of the type of tyrosine kinase inhibitor (TKI) used. In the MOST study, the budget impact analysis showed a total expense of €3,238,602.17, whereas the cost estimation according to median progression-free survival from pivotal phase III trials was €1,813,557.88. CONCLUSION: Good regional adherence and compliance to the diagnostic-therapeutic pathway defined for patients with nonsquamous NSCLC was shown. mTTF did not significantly differ among the three targeted TKIs. Our budget impact analysis suggests the potential application of real-world data in the process of drug price negotiation. IMPLICATIONS FOR PRACTICE: The MOST study is a real-world data collection reporting a multicenter adherence and compliance to diagnostic-therapeutic pathways defined for patients with epidermal growth factor receptor-mutant non-small cell lung cancer. This represents an essential element of evidence-based medicine, providing information on patients and situations that may be challenging to assess using only data from randomized controlled trials, e.g., turn-around time of diagnostic tests, treatment compliance and persistence, guideline adherence, challenging-to-treat populations, drug safety, comparative effectiveness, and cost effectiveness. This study may be of interest to various stakeholders (patients, clinicians, and payers), providing a meaningful picture of the value of a given therapy in routine clinical practice.

Nine questions on energy decomposition analysis.

The paper collects the answers of the authors to the following questions: Is the lack of precision in the definition of many chemical concepts one of the reasons for the coexistence of many partition schemes? Does the adoption of a given partition scheme imply a set of more precise definitions of the underlying chemical concepts? How can one use the results of a partition scheme to improve the clarity of definitions of concepts? Are partition schemes subject to scientific Darwinism? If so, what is the influence of a community's sociological pressure in the "natural selection" process? To what extent does/can/should investigated systems influence the choice of a particular partition scheme? Do we need more focused chemical validation of Energy Decomposition Analysis (EDA) methodology and descriptors/terms in general? Is there any interest in developing common benchmarks and test sets for cross-validation of methods? Is it possible to contemplate a unified partition scheme (let us call it the "standard model" of partitioning), that is proper for all applications in chemistry, in the foreseeable future or even in principle? In the end, science is about experiments and the real world. Can one, therefore, use any experiment or experimental data be used to favor one partition scheme over another? © 2019 Wiley Periodicals, Inc.

Assessing the Strength of Metal-Metal Interactions.

A proper comparison between bond strengths of different atom pairs is relevant only for the same formal bond order (BO) of atomic interactions, e.g., for single bonds, because it is clear that the higher is the BO or the number of the electron pairs responsible of bonding, the stronger is the bond. For the metal-metal interactions, such a comparison of the bond strengths is especially problematic because formal BOs may differ from the effective ones by more than 1 v.u. (valence units). In this paper, we investigated the strength of bonding and its correlation to structural parameters (bond length/BO) for 24 metal-metal pairs. A simple way of the BO and bond-strength analysis was proposed and verified on the transition metal dimers. In contrast to the previous studies, the effective BOs were not calculated from spectroscopic data or related to reference compounds, but determined independently based on the Pauling model and bond valence parameters obtained from recent quantum chemistry data. To characterize the bond strength, we used the force constants based on the available experimental or DFT data of stretching frequencies. A linear correlation between the effective BOs and force constants of the metal-metal bonds, which was confirmed in this work, allows for prediction of the stretching frequencies according to the effective BOs (and/or the bond lengths) and vice versa.

Spin density accuracy and distribution in azido Cu(II) complexes: A source function analysis.

Magnetic properties of open-shell systems depend on their unpaired electron density distribution. Accurate spin density (SD) is difficult to retrieve, both from polarized neutron diffraction (PND) data and from quantum approaches, and its interpretation is not trivial. The Source Function is a useful tool to interpret SD distributions and their accuracy. It is here applied to analyze and compare the theoretical SD in a weakly ferromagnetically coupled end-end azido dicopper complex with that in a strongly-coupled end-on complex. The Source Function enables to highlight the origin of the SD differences between the two dicopper complexes and among adopted computational approaches (CASSCF, DFT, UHF). Further insight is provided by partial Source Function SD reconstructions using given subsets of atoms. DFT methods exaggerate electron sharing between copper and the ligands, causing spin delocalization toward them and overestimating metal-ligand spin polarization, while underestimating CASSCF spin information transmission between atoms. CAS(10,10) SD is closer to the PND SD than other adopted methods © 2018 Wiley Periodicals, Inc.

An Electron Density Source-Function Study of DNA Base Pairs in Their Neutral and Ionized Ground States†.

The source function (SF) decomposes the electron density at any point into contributions from all other points in the molecule, complex, or crystal. The SF "illuminates" those regions in a molecule that most contribute to the electron density at a point of reference. When this point of reference is the bond critical point (BCP), a commonly used surrogate of chemical bonding, then the SF analysis at an atomic resolution within the framework of Bader's Quantum Theory of Atoms in Molecules returns the contribution of each atom in the system to the electron density at that BCP. The SF is used to locate the important regions that control the hydrogen bonds in both Watson-Crick (WC) DNA dimers (adenine:thymine (AT) and guanine:cytosine (GC)) which are studied in their neutral and their singly ionized (radical cationic and anionic) ground states. The atomic contributions to the electron density at the BCPs of the hydrogen bonds in the two dimers are found to be delocalized to various extents. Surprisingly, gaining or loosing an electron has similar net effects on some hydrogen bonds concealing subtle compensations traced to atomic sources contributions. Coarser levels of resolutions (groups, rings, and/or monomers-in-dimers) reveal that distant groups and rings often have non-negligible effects especially on the weaker hydrogen bonds such as the third weak CH⋅⋅⋅O hydrogen bond in AT. Interestingly, neither the purine nor the pyrimidine in the neutral or ionized forms dominate any given hydrogen bond despite that the former has more atoms that can act as source or sink for the density at its BCP. © 2018 Wiley Periodicals, Inc.

Probing Cyclic π-Electron Delocalization in an Imidazol-2-ylidene and a Corresponding Imidazolium Salt.

The extent of cyclic π-electron delocalization in the N-heterocyclic ring of an imidazol-2-ylidene (i.e., 1,3,4,5-tetramethylimidazol-2-ylidene) and its corresponding imidazolium salt (i.e., 1,3,4,5-tetramethylimidazolium chloride) has been investigated theoretically by using Bader's quantum theory of atoms in molecules (QTAIM) descriptors, delocalization indices, electron localizability indicators (ELI-Ds), and the source function tool. In addition, the experimental electron density distribution for the imidazolium salt has been obtained and analyzed from 100 K X-ray diffraction data. A significant drop is found in the ellipticity of the electron density along the Ccarbene -N bond path in the imidazol-2-ylidene. This is shown to be a natural consequence of the σ lone pair of the Ccarbene atom, which overwhelms the π-electron density, rather than a sign of a significantly diminished degree of π-electron delocalization in the imidazol-2-ylidene compared to its imidazolium salt. In fact, the source functions, the ELI-Ds, and the delocalization indices all probe a quite similar extent of cyclic π-electron delocalization in the N-heterocyclic rings of the two compounds.