Excited states of polonium(IV): electron correlation and spin-orbit coupling in the Po4+ free ion and in the bare and solvated [PoCl5]- and [PoCl6]2- complexes.

Polonium (Po, Z = 84) is a main-block element with poorly known physico-chemical properties. Not much information has been firmly acquired since its discovery by Marie and Pierre Curie in 1898, especially regarding its speciation in aqueous solution and spectroscopy. In this work, we revisit the absorption properties of two complexes, [PoCl5]- and [PoCl6]2-, using quantum mechanical calculations. These complexes have the potential to exhibit a maximum absorption at 418 nm in HCl medium (for concentrations of 0.5 mol L-1 and above). Initially, we examine the electronic spectra of the Po4+ free ion and of its isoelectronic analogue, Bi3+, in the spin-orbit configuration interaction (SOCI) framework. Our findings demonstrate that the SOCI matrix should be dressed with correlated electronic energies and that the quality of the spectra is largely improved by decontracting the reference states at the complete active space plus singles (CAS + S) level. Subsequently, we investigate the absorption properties of the [PoCl5]- and [PoCl6]2- complexes in two stages. Firstly, we perform methodological tests at the MP2/def2-TZVP gas phase geometries, indicating that the decontraction of the reference states can be skipped without compromising the accuracy significantly. Secondly, we study the solution absorption properties by means of single-point calculations performed at the solvated geometries, obtained by an implicit solvation treatment or a combination of implicit and explicit solvation. Our results highlight the importance of saturating the first coordination sphere of the PoIV ion to obtain a qualitatively correct picture. Finally, we conclude that the known-for-decades 418 nm peak could be attributed to a mixture of both the [PoCl5(H2O)]- and [PoCl6]2- complexes. This finding not only aligns with the behaviour of the analogous BiIII ion under similar conditions but also potentially provides an explanation for previous discrepancies in the literature.

Coordination and thermodynamic properties of aqueous protactinium(V) by first-principle calculations.

Protactinium (Z = 91) is a very rare actinide with peculiar physico-chemical properties. Indeed, although one may naively think that it behaves similarly to either thorium or uranium by its position in the periodic table, it may in fact follow its own rules. Because of the quite small energy gap between its valence shells (in particular the 5f and 6d ones) and also the strong influence of relativistic effects on its properties, it is actually a challenging element for theoretical chemists. In this article, we combine experimental information, chemical arguments and standard first-principle calculations, complemented by implicit and explicit solvation, to revisit the stepwise complexation of aqueous protactinium(V) with sulfate and oxalate dianionic ligands (SO42- and C2O42-, respectively). From a methodological viewpoint, we notably conclude that it is necessary to at least saturate the coordination sphere of protactinium(V) to reach converged equilibrium constant values. Furthermore, in the case of single complexations (i.e. with one sulfate or oxalate ligand bound in the bidentate fashion), we show that it is necessary to maintain the coordination of one hydroxyl group, present in the supposed [PaO(OH)]2+ precursor, to obtain coherent complexation constants. Therefore, we predict that this hydroxyl group is maintained in the formation of 1 : 1 complexes while we confirm that it is withdrawn when coordinating three sulfate or oxalate ligands. Finally, we stress that this work is a first step toward the future use of theoretical predictions to elucidate the enigmatic chemistry of protactinium in solution.

Generalization aspect of accurate machine learning models for CSI-based localization.

Localization is the process of determining the position of an entity in a given coordinate system. Due to its wide range of applications (e.g. autonomous driving, Internet-of-Things), it has gained much focus from the industry and academia. Channel State Information (CSI) has overtaken Received Signal Strength Indicator (RSSI) to achieve localization given its temporal stability and rich information. In this paper, we extend our previous work by combining classical and deep learning methods in an attempt to improve the localization accuracy using CSI. We then test the generalization aspect of both approaches in different environments by splitting the training and test sets such that their intersection is reduced when compared with uniform random splitting. The deep learning approach is a Multi Layer Perceptron Neural Network (MLP NN) and the classical machine learning method is based on K-nearest neighbors (KNN). The estimation results of both approaches outperform state-of-the-art performance on the same dataset. We illustrate that while the accuracy of both approaches deteriorates when tested for generalization, deep learning exhibits a higher potential to perform better beyond the training set. This conclusion supports recent state-of-the-art attempts to understand the behaviour of deep learning models.

Characterization of Uranyl Coordinated by Equatorial Oxygen: Oxo in UO3 versus Oxyl in UO3.

Uranium trioxide, UO3, has a T-shaped structure with bent uranyl, UO22+, coordinated by an equatorial oxo, O2-. The structure of cation UO3+ is similar but with an equatorial oxyl, O•-. Neutral and cationic uranium trioxide coordinated by nitrates were characterized by collision induced dissociation (CID), infrared multiple-photon dissociation (IRMPD) spectroscopy, and density functional theory. CID of uranyl nitrate, [UO2(NO3)3]- (complex A1), eliminates NO2 to produce nitrate-coordinated UO3+, [UO2(O•)(NO3)2]- (B1), which ejects NO3 to yield UO3 in [UO2(O)(NO3)]- (C1). Finally, C1 associates with H2O to afford uranyl hydroxide in [UO2(OH)2(NO3)]- (D1). IRMPD of B1, C1, and D1 confirms uranyl equatorially coordinated by nitrate(s) along with the following ligands: (B1) radical oxyl O•-; (C1) oxo O2-; and (D1) two hydroxyls, OH-. As the nitrates are bidentate, the equatorial coordination is six in A1, five in B1, four in D1, and three in C1. Ligand congestion in low-coordinate C1 suggests orbital-directed bonding. Hydrolysis of the equatorial oxo in C1 epitomizes the inverse trans influence in UO3, which is uranyl with inert axial oxos and a reactive equatorial oxo. The uranyl ν3 IR frequencies indicate the following donor ordering: O2-[best donor] ≫ O•-> OH-> NO3-.

The electron affinity of astatine.

One of the most important properties influencing the chemical behavior of an element is the electron affinity (EA). Among the remaining elements with unknown EA is astatine, where one of its isotopes, 211At, is remarkably well suited for targeted radionuclide therapy of cancer. With the At- anion being involved in many aspects of current astatine labeling protocols, the knowledge of the electron affinity of this element is of prime importance. Here we report the measured value of the EA of astatine to be 2.41578(7) eV. This result is compared to state-of-the-art relativistic quantum mechanical calculations that incorporate both the Breit and the quantum electrodynamics (QED) corrections and the electron-electron correlation effects on the highest level that can be currently achieved for many-electron systems. The developed technique of laser-photodetachment spectroscopy of radioisotopes opens the path for future EA measurements of other radioelements such as polonium, and eventually super-heavy elements.

Design and Evaluation of Flooding-Based Location Service in Vehicular Ad Hoc Networks.

Location-based routing protocols for vehicular ad hoc networks (VANETs) use location information to determine routing decisions. This information is provided by a location service that is queried by nodes in order to properly forward packets to communication partners. This paper presents the semiflooding location service, a proactive flooding-based location service that drastically reduces the number of update packets sent over the network compared to traditional flooding-based location services. This goal is achieved by each node partially forwarding location information. We present both deterministic and probabilistic approaches for this algorithm, which remains very simple. A mathematical model is proposed to show the effectiveness of this solution. The cases of homogeneous 1D, 2D, and 3D networks were studied for both deterministic and probabilistic forwarding decisions. We compare our algorithm with simple flooding and with the multipoint-relay (MPR) flooding of the optimized-link-state-routing (OLSR) protocol, and we show that our algorithm, despite being very simple, has excellent scalability properties. The mean number of generated messages ranges with the mean number of the neighbors of one random network node.

Environment Monitoring for Anomaly Detection System Using Smartphones.

Currently, the popularity of smartphones with networking capabilities equipped with various sensors and the low cost of the Internet have opened up great opportunities for the use of smartphones for sensing systems. One of the most popular applications is the monitoring and the detection of anomalies in the environment. In this article, we propose to enhance classic road anomaly detection methods using the Grubbs test on a sliding window to make it adaptive to the local characteristics of the road. This allows more precision in the detection of potholes and also building algorithms that consume less resources on smartphones and adapt better to real conditions by applying statistical outlier tests on current threshold-based anomaly detection methods. We also include a clustering algorithm and a mean shift-based algorithm to aggregate reported anomalies on data to the server. Experiments and simulations allow us to confirm the effectiveness of the proposed methods.

Over-voluming predicted by pre-operative planning in 24% of total knee arthroplasty.

PURPOSE: Numerous studies demonstrated that prosthetic overhang and over-sizing cause pain and stiffness following total knee arthroplasty (TKA), but none considered volume changes within the joint capsule. This study was designed to investigate differences in volumes of resected bone compared to implanted components in TKA, and to determine the incidence and factors related to 'over-voluming'. METHODS: Three-dimensional reconstructions were created from 100 magnetic resonance imaging scans taken to design patient-specific instruments for TKA. The preoperative simulations were used to calculate the volume ratio (VR) by dividing volume of planned components by that of planned bone resections. Uni- and multi-variable linear regressions were performed to determine associations between 'over-voluming' (VR > 1.0) and gender, implant size and version (standard versus narrow), osteophytes, resection levels, external rotation of the femoral component, hip-knee-ankle (HKA) angle, mechanical lateral distal femoral angle (mLDFA), and mechanical medial proximal tibial angle (mMPTA). RESULTS: The overall implant/bone volume ratio was 0.91 ± 0.11 (range 0.63-1.16) with 'over-voluming' observed in 24 knees. Multi-variable regression confirmed over-voluming to be associated with lower mLDFA (OR 0.66; CI 0.45-0.93; p = 0.026) and extensive osteophytes (OR 0.14; CI 0.03-0.61; p = 0.014), but not HKA angle (OR 0.98; CI 0.76-1.26; p = n.s.). CONCLUSIONS: Over-voluming was observed in 24% of knees, in which the implant volume exceeded the resected volume by up to 16%. Over-voluming was associated with intra-articular femoral valgus (low mLDFA), but not directly associated with tibial deformity (mMPTA) or HKA angle. Over-voluming could be associated with prosthetic overhang or excessive tensions within the joint capsule, and, therefore, contribute to unexplained pain and stiffness following TKA. LEVEL OF EVIDENCE: IV, Retrospective cohort study.

Timeline representation of clinical data: usability and added value for pharmacovigilance.

BACKGROUND: Pharmacovigilance consists in monitoring and preventing the occurrence of adverse drug reactions (ADR). This activity requires the collection and analysis of data from the patient record or any other sources to find clues of a causality link between the drug and the ADR. This can be time-consuming because often patient data are heterogeneous and scattered in several files. To facilitate this task, we developed a timeline prototype to gather and classify patient data according to their chronology. Here, we evaluated its usability and quantified its contribution to routine pharmacovigilance using real ADR cases. METHODS: The timeline prototype was assessed using the biomedical data warehouse eHOP (from entrepôt de données biomédicales de l'HOPital) of the Rennes University Hospital Centre. First, the prototype usability was tested by six experts of the Regional Pharmacovigilance Centre of Rennes. Their experience was assessed with the MORAE software and a System and Usability Scale (SUS) questionnaire. Then, to quantify the timeline contribution to pharmacovigilance routine practice, three of them were asked to investigate possible ADR cases with the "Usual method" (analysis of electronic health record data with the DxCare software) or the "Timeline method". The time to complete the task and the data quality in their reports (using the vigiGrade Completeness score) were recorded and compared between methods. RESULTS: All participants completed their tasks. The usability could be considered almost excellent with an average SUS score of 82.5/100. The time to complete the assessment was comparable between methods (P = 0.38) as well as the average vigiGrade Completeness of the data collected with the two methods (P = 0.49). CONCLUSIONS: The results showed a good general level of usability for the timeline prototype. Conversely, no difference in terms of the time spent on each ADR case and data quality was found compared with the usual method. However, this absence of difference between the timeline and the usual tools that have been in use for several years suggests a potential use in pharmacovigilance especially because the testers asked to continue using the timeline after the evaluation.

Factors influencing the development of primary care data collection projects from electronic health records: a systematic review of the literature.

BACKGROUND: Primary care data gathered from Electronic Health Records are of the utmost interest considering the essential role of general practitioners (GPs) as coordinators of patient care. These data represent the synthesis of the patient history and also give a comprehensive picture of the population health status. Nevertheless, discrepancies between countries exist concerning routine data collection projects. Therefore, we wanted to identify elements that influence the development and durability of such projects. METHODS: A systematic review was conducted using the PubMed database to identify worldwide current primary care data collection projects. The gray literature was also searched via official project websites and their contact person was emailed to obtain information on the project managers. Data were retrieved from the included studies using a standardized form, screening four aspects: projects features, technological infrastructure, GPs' roles, data collection network organization. RESULTS: The literature search allowed identifying 36 routine data collection networks, mostly in English-speaking countries: CPRD and THIN in the United Kingdom, the Veterans Health Administration project in the United States, EMRALD and CPCSSN in Canada. These projects had in common the use of technical facilities that range from extraction tools to comprehensive computing platforms. Moreover, GPs initiated the extraction process and benefited from incentives for their participation. Finally, analysis of the literature data highlighted that governmental services, academic institutions, including departments of general practice, and software companies, are pivotal for the promotion and durability of primary care data collection projects. CONCLUSION: Solid technical facilities and strong academic and governmental support are required for promoting and supporting long-term and wide-range primary care data collection projects.

Heptavalent Neptunium in a Gas-Phase Complex: (NpVIIO3+)(NO3-)2.

A central goal of chemistry is to achieve ultimate oxidation states, including in gas-phase complexes with no condensed phase perturbations. In the case of the actinide elements, the highest established oxidation states are labile Pu(VII) and somewhat more stable Np(VII). We have synthesized and characterized gas-phase AnO3(NO3)2- complexes for An = U, Np, and Pu by endothermic NO2 elimination from AnO2(NO3)3-. It was previously demonstrated that the PuO3+ core of PuO3(NO3)2- has a Pu-O• radical bond such that the oxidation state is Pu(VI); it follows that in UO3(NO3)2- it is the stable U(VI) oxidation state. On the basis of the relatively more facile synthesis of NpO3(NO3)2-, a Np(VII) oxidation state is inferred. This interpretation is substantiated by reactivity of the three complexes: NO2 spontaneously adds to UO3(NO3)2- and PuO3(NO3)2- but not to NpO3(NO3)2-. This unreactive character is attributed to a Np(VII)O3+ core with three stable Np═O bonds, this in contrast to reactive U-O• and Pu-O• radical bonds. The computed structures and reaction energies for the three AnO3(NO3)2- support the conclusion that the oxidation states are U(VI), Np(VII), and Pu(VI). The results establish the extreme Np(VII) oxidation state in a gas-phase complex, and demonstrate the inherently greater stability of Np(VII) versus Pu(VII).

An Integrated Workflow For Secondary Use of Patient Data for Clinical Research.

This work proposes an integrated workflow for secondary use of medical data to serve feasibility studies, and the prescreening and monitoring of research studies. All research issues are initially addressed by the Clinical Research Office through a research portal and subsequently redirected to relevant experts in the determined field of concentration. For secondary use of data, the workflow is then based on the clinical data warehouse of the hospital. A datamart with potentially eligible research candidates is constructed. Datamarts can either produce aggregated data, de-identified data, or identified data, according to the kind of study being treated. In conclusion, integrating the secondary use of data process into a general research workflow allows visibility of information technologies and improves the accessability of clinical data.

Synthesis and structures of plutonyl nitrate complexes: is plutonium heptavalent in PuO3(NO3)2(-) ?

Gas-phase plutonium nitrate anion complexes were produced by electrospray ionization (ESI) of a plutonium nitrate solution. The ESI mass spectrum included species with all four of the common oxidation states of plutonium: Pu(III), Pu(IV), Pu(V), and Pu(VI). Plutonium nitrate complexes were isolated in a quadrupole ion trap and subjected to collision-induced dissociation (CID). CID of complexes of the general formula PuOx(NO3)y(-) resulted in the elimination of NO2 to produce PuOx+1(NO3)y-1(-), which in most cases corresponds to an increase in the oxidation state of plutonium. Plutonyl species, Pu(V)O2(NO3)2(-) and Pu(VI)O2(NO3)3(-), were produced from Pu(III)(NO3)4(-) and Pu(IV)(NO3)5(-), respectively, by the elimination of two NO2 molecules. CID of Pu(VI)O2(NO3)3(-) resulted in NO2 elimination to yield PuO3(NO3)2(-), in which the oxidation state of plutonium could be VII, a known oxidation state in condensed phase but not yet in the gas phase. Density functional theory confirmed the nature of Pu(V)O2(NO3)2(-) and Pu(VI)O2(NO3)3(-) as plutonyl(V/VI) cores coordinated by bidentate equatorial nitrate ligands. The computed structure of PuO3(NO3)2(-) is essentially a plutonyl(VI) core, Pu(VI)O2(2+), coordinated in the equatorial plane by two nitrate ligands and one radical oxygen atom. The computations indicate that in the ground spin-orbit free state of PuO3(NO3)2(-), the unpaired electron of the oxygen atom is antiferromagnetically coupled to the spin-triplet state of the plutonyl core. The results indicate that Pu(VII) is not a readily accessible oxidation state in the gas phase, despite that it is stable in solution and solids, but rather that a Pu(VI)-O· bonding configuration is favored, in which an oxygen radical is involved.

QTAIM Analysis in the Context of Quasirelativistic Quantum Calculations.

Computational chemistry currently lacks ad hoc tools for probing the nature of chemical bonds in heavy and superheavy-atom systems where the consideration of spin-orbit coupling (SOC) effects is mandatory. We report an implementation of the Quantum Theory of Atoms-In-Molecules in the framework of two-component relativistic calculations. Used in conjunction with the topological analysis of the Electron Localization Function, we show for astatine (At) species that SOC significantly lowers At electronegativity and boosts its propensity to make charge-shift bonds. Relativistic spin-dependent effects are furthermore able to change some bonds from mainly covalent to charge-shift type. The implication of the disclosed features regarding the rationalization of the labeling protocols used in nuclear medicine for (211)At radioisotope nicely illustrates the potential of the introduced methodology for investigating the chemistry of (super)heavy elements.

Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: design, synthesis, and validation.

Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 µM. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.

Introducing the ELF Topological Analysis in the Field of Quasirelativistic Quantum Calculations.

We present an original formulation of the electron localization function (ELF) in the field of relativistic two-component DFT calculations. Using I2 and At2 species as a test set, we show that the ELF analysis is suitable to evaluate the spin-orbit effects on the electronic structure. Beyond these examples, this approach opens up new opportunities for the bonding analysis of large molecular systems involving heavy and superheavy elements.

Assessment of an effective quasirelativistic methodology designed to study astatine chemistry in aqueous solution.

A cost-effective computational methodology designed to study astatine (At) chemistry in aqueous solution has been established. It is based on two-component spin-orbit density functional theory calculations and solvation calculations using the conductor-like polarizable continuum model in conjunction with specific astatine cavities. Theoretical calculations are confronted with experimental data measured for complexation reactions between metallic forms of astatine (At(+) and AtO(+)) and inorganic ligands (Cl(-), Br(-) and SCN(-)). For each reaction, both 1:1 and 1:2 complexes are evidenced. The experimental trends regarding the thermodynamic constants (K) can be reproduced qualitatively and quantitatively. The mean signed error on computed Log K values is -0.4, which corresponds to a mean signed error smaller than 1 kcal mol(-1) on free energies of reaction. Theoretical investigations show that the reactivity of cationic species of astatine is highly sensitive to spin-orbit coupling and solvent effects. At the moment, the presented computational methodology appears to be the only tool to gain an insight into astatine chemistry at a molecular level.

Structural features and protonation site of epibatidine in the gas phase: an investigation through infrared multiphoton dissociation spectroscopy and computational chemistry.

The gas phase structures of epibatidine, one of the most potent agonists of nicotinic acetylcholine receptors (nAChRs), are determined by means of infrared multiphoton dissociation (IRMPD) spectroscopy and quantum chemistry calculations. Comparison of the experimental and theoretical spectra provides evidence that about 15% of epibatidine is protonated on the Nsp(2) nitrogen in the gas phase. In contrast, the computational study of deschloroepibatidine shows that in the gas phase, the molecule is present only protonated on the Nsp(2) nitrogen. The main minima of the Nsp(2) protonated forms of the two molecules are strongly stabilized by intramolecular CH···Nsp(3) hydrogen bonds. The fundamental insights obtained in the present study on these two important nAChRs agonists show how subtle chemical modifications can have a deep impact on important physicochemical properties.

Electrochemical synthesis and characterisation of alternating tripyridyl-dipyrrole molecular strands with multiple nitrogen-based donor-acceptor binding sites.

Synthesis of alternating pyridine-pyrrole molecular strands composed of two electron-rich pyrrole units (donors) sandwiched between three pyridinic cores (acceptors) is described. The envisioned strategy was a smooth electrosynthesis process involving ring contraction of corresponding tripyridyl-dipyridazine precursors. 2,6-Bis[6-(pyridazin-3-yl)]pyridine ligands 2a-c bearing pyridine residues at the terminal positions were prepared in suitable quantities by a Negishi metal cross-coupling procedure. The yields of heterocyclic coupling between 2-pyridyl zinc bromide reagents 12a-c and 2,6-bis(6-trifluoromethanesulfonylpyridazin-3-yl)pyridine increased from 68 to 95% following introduction of electron-donating methyl groups on the metallated halogenopyridine units. Favorable conditions for preparative electrochemical reduction of tripyridyl-dipyridazines 2b,c were established in THF/acetate buffer (pH 4.6)/acetonitrile to give the targeted 2,6-bis[5-(pyridin-2-yl)pyrrol-2-yl]pyridines 1b and 1c in good yields. The absorption behavior of the donor-acceptor tripyridyl-dipyrrole ligands was evaluated and compared to theoretical calculations. Highly fluorescent properties of these chromophores were found (ν(em)≈2 × 10(4) cm(-1) in MeOH and CH(2)Cl(2)), and both pyrrolic ligands exhibit a remarkable quantum yield in CH(2)Cl(2) (φ(f)=0.10). Structural studies in the solid state established the preferred cis conformation of the dipyrrolic ligands, which adopting a planar arrangement with an embedded molecule of water having a complexation energy exceeding 10 kcal mol(-1). The ability of the tripyridyl-dipyrrole to complex two copper(II) ions in a pentacoordinate square was investigated.

An enthalpic scale of hydrogen-bond basicity. 4. Carbon pi bases, oxygen bases, and miscellaneous second-row, third-row, and fourth-row bases and a survey of the 4-fluorophenol affinity scale.

The thermodynamics of the O-H...B hydrogen bond (HB) has been determined in CCl(4) by FTIR spectrometry for a wide variety of carbon pi bases, oxygen bases, and miscellaneous first- to fourth-row bases, using 4-fluorophenol as a reference hydrogen-bond donor (HBD). After inclusion of previously studied nitrogen, sulfur, and halogen bases, this 4-fluorophenol affinity scale contains 314 varied organic bases and ranges over 40 kJ mol(-1). The 4-fluorophenol affinity scale in CCl(4) is shown to be applicable to most HBDs in most media, provided a small family dependence is taken into account. The HB affinity orders are quantitatively established according to the atomic acceptor site or to its bearing functional group. A comprehensive survey of the influence of substituents on these affinity orders is then achieved, considering electronic and steric effects, as well as effects of vinylogy or iminology. Iminology is found to be more efficient than vinylogy for transmitting resonance effects. Steric effects are shown to be less important in HB affinity than in HB basicity since they mainly act on the HB entropy. The spatial proximity of two acceptor sites can favor complexation through three-center hydrogen bonds, leading to superhydrogen-bond bases on the affinity scale.