Jorge Charry

Classifying interactions is key in the physical sciences, and bonding mechanisms in matter-antimatter systems remain particularly enigmatic. Here, we focus on a paradigmatic example of positronium hydride (PsH) dimer composed of two protons, two positrons, and four electrons, whose bonding nature has been previously described as either ionic, covalent, or van der Waals like. Accurate quantum Monte Carlo calculations show that the two positrons occupy a delocalized molecular orbital that envelopes the two hydrogen anions and responds as a collective dipole to an applied electric field. This positronic bonding stems from quantum correlations that resemble a single covalent bond formed between negatively charged pseudonuclei, but with a bond strength commensurate with the traditional van der Waals interaction. Our findings suggest that the ability to form delocalized proto-bonds is a more general property of quantum systems and could be present in a broader class of particles, antiparticles, and quasiparticles interacting with matter.

We present the first open access version of the QMeCha (Quantum MeCha /’mεkə/) code, a quantum Monte Carlo package developed to study many-body interactions between different types of quantum particles, with a modular and easy-to-expand structure. QMeCha is now available under a CC BY-NC-ND license through the repository github.com/QMeCha. The present code has been developed to solve the Hamiltonian of a system that can include nuclei and fermions of different mass and charge, e.g., electrons and positrons, embedded in an environment of classical charges and quantum Drude oscillators. To approximate the ground state of this many-particle operator, the code features different wavefunctions. For the fermionic particles, beyond the traditional Slater determinant, QMeCha also includes geminal functions, such as the Pfaffian, and presents different types of explicit correlation terms in Jastrow factors. The classical point charges and quantum Drude oscillators, described through different variational Ansätze, are used to model a molecular environment capable of explicitly describing dispersion, polarization, and electrostatic effects experienced by the nuclear and fermionic subsystems. To integrate these wavefunctions, efficient variational Monte Carlo and diffusion Monte Carlo protocols have been developed, together with a robust wavefunction optimization procedure that features correlated sampling.

Positronium (Ps) atoms are highly sensitive probes of condensed-phase structure and dynamics, yet their theoretical description in complex molecular environments remains challenging. We present an extension of our QM/MM protocol to investigate Ps in methanol and ethanol, building on our earlier study in water. Classical Monte Carlo simulations employing newly parametrized Ps-solvent force fields reveal well-defined cavity structures, whose sizes are consistent with hydrated Ps and systematically smaller than those predicted by empirical bubble models. Multicomponent quantum calculations employing the Any Particle Molecular Orbital (APMO) method have identified physically meaningful cavity states, characterized by substantial electron-positron overlap, and have ruled out spurious surface states as artifacts of the QM region truncation. While vertical detachment energies are insensitive primarily to solvent structure, computed pick-off annihilation lifetimes showed a marked dependence on cavity size. Employing orbital-dependent enhancement factors, our results achieve good agreement with experimental PALS data for both solvents. This study demonstrates the transferability and predictive power of our QM/MM protocol for Ps, providing a framework that can be systematically extended to more complex solvents and biological environments, thereby advancing the theoretical interpretation of Ps annihilation in complex systems.

Electronic density and dipole changes of a molecular system in the presence of an external electric field along its bond dissociation coordinate to define three chemically relevant regions: bonded, bond-breaking and dissociation.

A novel, positron-driven chemical bond is shown to fundamentally stabilize the Be ₂ dimer through a unique two-stage mechanism of e ⁺ redistribution.

Predicting the binding affinity of ligands to protein pockets is key in the drug design pipeline. The flexibility of ligand-pocket motifs arises from a range of attractive and repulsive electronic interactions during binding. Accurately accounting for all interactions requires robust quantum-mechanical (QM) benchmarks, which are scarce for ligand-pocket systems. Additionally, disagreement between “gold standard” Coupled Cluster (CC) and Quantum Monte Carlo (QMC) methods casts doubt on many benchmarks for larger non-covalent systems. We introduce the “QUantum Interacting Dimer” (QUID) benchmark framework containing 170 non-covalent (non-)equilibrium systems modeling chemically and structurally diverse ligand-pocket motifs. Symmetry-adapted perturbation theory shows that QUID broadly covers non-covalent binding motifs and energetic contributions. Robust binding energies are obtained using complementary CC and QMC methods, achieving agreement of 0.5 kcal/mol. The benchmark data analysis reveals that several dispersion-inclusive density functional approximations provide accurate energy predictions, though their atomic van der Waals forces differ in magnitude and orientation. Contrarily, semiempirical methods and empirical force fields require improvements in capturing non-covalent interactions (NCIs) for out-of-equilibrium geometries. The wide span of NCIs, highly accurate interaction energies, and analysis of molecular properties take QUID beyond the “gold standard” for QM benchmarks of ligand-protein systems.

Predicting the binding affinity of ligand molecules to protein pockets is a key step in the drug design pipeline. The flexibility of ligand-pocket motifs arises from a wide range of attractive and repulsive electronic interactions invoked upon binding. Accurately accounting for all these interactions on equal footing requires robust quantum-mechanical (QM) benchmarks, which are scarce for ligand-pocket systems. In addition, the puzzling disagreement between ``gold standard'' Coupled Cluster (CCSD(T)) and Quantum Monte Carlo (QMC) methods [Nat. Commun. 12, 3927 (2021)] casts doubt on many existing benchmarks for larger non-covalent systems. Here, we introduce the ``Quantum Interacting Dimer'' (QUID) benchmark framework containing 170 non-covalent systems spanning equilibrium and non-equilibrium geometries that model chemically and structurally diverse ligand-pocket motifs. Symmetry-adapted perturbation theory shows that QUID broadly covers non-covalent binding motifs and energetic (exchange-repulsion, electrostatic, induction, and dispersion) contributions. Robust and reproducible binding energies are obtained using two complementary QM methods: LNO-CCSD(T) and QMC, achieving mutual agreement of 0.3 kcal/mol. Analysis of this benchmark data reveals that several dispersion-inclusive density functional approximations provide accurate energy predictions, though they exhibit discrepancies in magnitude and orientation of atomic van der Waals forces, which could influence the dynamics of ligands within the pocket. On the contrary, semiempirical methods and widely used empirical force fields require improvements, particularly in capturing non-covalent interactions (NCIs) for out-of-equilibrium geometries. The wide span of molecular dipole moments and polarizabilities in QUID also demonstrates flexibility in designing pocket structures to achieve desired binding properties. Therefore, QUID sets a new ``platinum standard'' for reliable and reproducible QM benchmarks of NCIs in larger systems and enhances our understanding of biomolecular ligand-pocket interactions.

This study explores the energetic stability and physical properties of complexes formed by two halide anions (X⁻, Y⁻=F⁻, X⁻, Br⁻), and two positrons (Ps: positron‐electron pair). We combine electronic coupled cluster (CCSD(T)) calculations with positronic multicomponent renormalized partial third‐order propagator (MC‐REN‐PP3) calculations to effectively recover correlation energies. Analysis of potential energy curves confirms the energetic stability of these positronic molecules, with optimized structures identified as global minima. Further investigation of electron and positron densities reveals stabilization owing to the formation of two‐positron bonds. The global stability of the complexes contrasts with the metastable two‐positron‐bonded (PsH)₂, which energetically favors the emission of Ps₂. Comparative analysis of one‐ and two‐positron dihalides indicates that the addition of a positron to PsXY⁻ generally results in shorter bond distances, higher force constants, and lower dissociation energies, with exceptions due to differences in positron affinities of PsXY⁻ and Y⁻. We explore the analogy between two‐positron‐bonded dihalide systems and two‐electron‐bonded dialkali molecules AB, (A, B=Na, K, Rb). The bonding properties in two‐positron dihalides and their electronic dialkali analogs are comparable, displaying identical periodic trends. However, compared to their isoelectronic AB counterparts, the positron bonds in have shorter bond lengths, higher force constants, and higher bond energies.

We performed a computational study of positron attachment to hydrated amino acids, namely glycine, alanine, and proline in the zwitterionic form. We combined the sequential quantum mechanics/molecular mechanics (s-QM/MM) method with various levels of any particle molecular orbital (APMO) calculations. Consistent with previous studies, our calculations indicate the formation of energetically stable states for the isolated and microsolvated amino acids, in which the positron localizes around the carboxylate group. However, for the larger clusters, composed of 7 to 40 water molecules, hydrogen bonding between the solute and solvent molecules disfavors positron attachment to the amino acids, giving rise to surface states in which the positron is located around the water-vacuum interface. The analysis of positron binding energies, positronic orbitals, radial probability distributions, and annihilation rates consistently pointed out the change from positron-solute to positron-solvent states. Even with the inclusion of an electrostatic embedding around the aggregates, the positrons did not localize around the solute. Positron attachment to molecules in the gas phase is a well-established fact. The existence of hydrated positronic molecules could also be expected from the analogy with transient anion states, which are believed to participate in radiation damage. Our results indicate that positron attachment to hydrated biomolecules, even to zwitterions with negatively charged carboxylated groups, would not take place. For the larger clusters, in which positron-water interactions are favored, the calculations indicate an unexpectedly large contribution of the core orbitals to the annihilation rates, between 15 and 20%. Finally, we explored correlations between positron binding energies (PBEs) and dipole moments, as well as annihilation rates and PBEs, consistent with previous studies for smaller clusters.

Reliable numerical values of van der Waals (vdW) radii are required for constructing empirical force fields, vdW-inclusive density functional, and quantum-chemical methods, as well as for implicit solvent models. However, multiple definitions exist for vdW radii, involving either equilibrium or the closest contact distances between free or bonded atoms within molecules or crystals. For the paradigmatic case of the hydrogen atom, its reported vdW radius fluctuates between 2.15 and 3.70 Bohr depending on the definition, leading to a high uncertainty in calculations and different conceptual interpretations of noncovalent interactions. In this work, we systematically review different definitions and methodologies to establish the free and bonded vdW radii for hydrogen, based on equilibrium vdW distances in noncovalently bonded molecules, enveloping electron density cutoffs, noncovalent positron bonds in hydrogen anion dimer, vacuum virtual photon cloud caused by the hydrogen atom, and atomic dipole polarizability. By doing so, we show that the vdW radius of the free hydrogen atom is 3.16 ± 0.06 Bohr. By employing the most general and elegant definition of atomic vdW radius as a function of the atomic polarizability, we tabulate consistent values of vdW radii for all atoms in the periodic table up to Z = 118.