Geometric Optimization of Restricted-Open and Complete Active Space Self-Consistent Field Wave Functions.

We explore Riemannian optimization methods for Restricted-Open-shell Hartree-Fock (ROHF) and Complete Active Space Self-Consistent Field (CASSCF) methods. After showing that ROHF and CASSCF can be reformulated as optimization problems on so-called "flag manifolds", we review Riemannian optimization basics and their application to these specific problems. We compare these methods to traditional ones and find robust convergence properties without fine-tuning of numerical parameters. Our study suggests that Riemannian optimization is a valuable addition to orbital optimization for ROHF and CASSCF, warranting further investigation.

Transition Metal-Driven Selectivity in Direct C-H Arylation of Imidazo[2,1-b]Thiazole.

A selective direct arylation of the different Csp2-H bonds of imidazo[2,1-b]thiazole with (hetero) aryl halides can be achieved simply by switching from a palladium catalyst system to the use of stoichiometric amounts of copper. The observed selectivity, also rationalized by DFT calculations, can be explained by a change in the mechanistic pathways between electrophilic palladation and base-promoted C-H metalation.

Importance of Polarizable Embedding for Computing Optical Rotation: The Case of Camphor in Ethanol.

Solvation effects on optical rotation are notoriously challenging to model for computational chemistry, as the specific rotatory power of a molecule can vary wildly going from apolar to polar or even protic solvents. To address such a problem, we present a polarizable embedding implementation of an electric and magnetic response property based on density functional theory and the AMOEBA polarizable force field, and apply such an implementation to the study of the optical rotation of camphor in ethanol. By comparing a continuum model, and electrostatic and polarizable embedding QM/MM models, we observe that accounting for the environment's polarization gives rise to not only a different quantitative prediction, in very good agreement with experiments for the QM/AMOEBA model, but also to a very different qualitative picture, with the values of the optical rotation computed along a classical molecular dynamics trajectory with electrostatic embedding being statistically uncorrelated to the ones obtained with the polarizable description.

MBE-CASSCF Approach for the Accurate Treatment of Large Active Spaces.

We present a novel implementation of the complete active space self-consistent field (CASSCF) method that makes use of the many-body expanded full configuration interaction (MBE-FCI) method to incrementally approximate electronic structures within large active spaces. On the basis of a hybrid first-order algorithm employing both Super-CI and quasi-Newton strategies for the optimization of molecular orbitals, we demonstrate both computational efficacy and high accuracy of the resulting MBE-CASSCF method. We assess the performance of our implementation on a set of established numerical tests before applying MBE-CASSCF in the investigation of the triplet-quintet spin gap of iron(II) porphyrin with active spaces as large as 50 electrons in 50 orbitals.

Changing aromatic properties through stacking: the face-to-face dimer of Ni(II) bis(pentafluorophenyl)norcorrole.

Nuclear magnetic resonance (NMR) shielding constants have been calculated for Ni(II) bis(pentafluorophenyl)norcorrole and its face-to-face stacked dimer at the Hartree-Fock (HF), second-order Møller-Plesset perturbation theory (MP2), complete-active-space self-consistent-field (CASSCF) levels as well as at density functional theory (DFT) levels using several functionals. The calculated 1H NMR shielding constants agree rather well with the experimental ones. The shielding constants of N and Ni calculated at DFT, HF, and MP2 levels differ from those obtained in the CASSCF calculations due to near-degeneracy effects at the Ni atom. The calculated magnetically induced current densities show that the monomer is antiaromatic, sustaining a strong global paratropic ring current, and the dimer is aromatic, sustaining a strong diatropic ring current. Qualitatively the same current density is obtained at the employed levels of theory. The most accurate ring-current strengths are probably obtained at the MP2 level. The aromatic dimer has a short intermolecular distance of less than 3 Å. The intermolecular interaction changes the nature of the frontier orbitals leading to a formal double bond between the norcorrole macrocycles.

Step by step technique of Stentless Florence Robotic Intracorporeal Neobladder (FloRIN), does the ureteral management influence functional outcomes?

INTRODUCTION: Benefits and harms of avoid the sent placement during IntraCorporeal Neobladder configuration are still debated. Our objective was to describe the step-by-step technique of Florence intracorporeal neobladder (FloRIN) configuration performed with stentless procedure focusing on perioperative and mid-term functional outcomes. MATERIALS AND METHODS: In this single institution prospective randomized 1:1 series all consecutive patients underwent Robot-Assisted Radical Cystectomy (RARC) and FloRIN reconfiguration from January 2021 to March 2021 were enrolled. Functional perioperative and mid-term outcomes were gathered. Postoperative complications were graded according to Clavien-Dindo classification and divided in early (<30 days from discharge) and delayed (>30 days). RESULTS: Overall, 10 patients were included in the analysis. Of these, the 50.0% was treated with Stentless FloRIN. In terms of baseline features, no differences were recorded between the two groups. Median age was 65 and 66 years while median BMI was 27 and 25 in the stentless and in the stent group, respectively. Concerning intraoperative variables, no intraoperative complications as well as open conversion occurred among both groups. As regard introperative features, a shorter console time was associated with stentless procedure (331 min vs 365 min). In terms of perioperative outcomes, canalization and time to drainage removal didn't differ between groups while length of hospital stay was significantly lower in stentless group 10 days versus 14 days. Early and delayed postoperative complication rate was not influenced by the ureteral management at a preliminary assessment with comparable rates of Clavien Dindo ⩾ 3a between the two groups. Mid-term functional outcomes did not differ between groups in terms of kidney function loss. CONCLUSIONS: FloRIN with Stentless technique showed functional and perioperative preliminary outcomes comparable with the standard ureteral management strategy. Further series with longer functional follow-up assessment will be needed to confirm our preliminary results.

The OpenMMPol library for polarizable QM/MM calculations of properties and dynamics.

We present a new library designed to provide a simple and straightforward way to implement QM/AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications) and other polarizable QM/MM (Molecular Mechanics) methods based on induced point dipoles. The library, herein referred to as OpenMMPol, is free and open-sourced and is engineered to address the increasing demand for accurate and efficient QM/MM simulations. OpenMMPol is specifically designed to allow polarizable QM/MM calculations of ground state energies and gradients and excitation properties. Key features of OpenMMPol include a modular architecture facilitating extensibility, parallel computing capabilities for enhanced performance on modern cluster architectures, a user-friendly interface for intuitive implementation, and a simple and flexible structure for providing input data. To show the capabilities offered by the library, we present an interface with PySCF to perform QM/AMOEBA molecular dynamics, geometry optimization, and excited-state calculation based on (time-dependent) density functional theory.

Breaking the Rules: On the Relative Stability of Some Methylencyclopropane and Methylcyclopropene Derivatives.

The structure of the spirocyclic product obtained by reacting catechol with 1,1-dichloro-2-(chloromethyl)cyclopropane is shown by NMR and X-ray analysis to be that of a 2-methylcyclopropene (MeCP), instead of the previously reported 2-methylenecyclopropane (MCP) one. The study of the equilibration between the two isomeric forms by experimental and computational means (including both Density Functional Theory - DFT - and Coupled Cluster with single, double, and perturbative triple excitations - CCSD(T) - calculations) revealed that, at variance with most of the alkylidenecyclopropane/alkylcyclopropene systems described to date, for the compounds of the present study the MeCP derivative is more stable by≈ 2.5-3.0 Kcal mol-1 than the MCP one. The extension of the DFT and CCSD(T) study to other spiro-MCP/MeCP pairs suggests that the origin of the unexpected shift of the equilibrium position can be tracked back to a combination of electronic and ring-strain effects. These findings lead to re-think a long-standing, and substantially undisputed belief in the area of unsaturated cyclopropane derivatives.

Unraveling Water Solvation Effects with Quantum Mechanics/Molecular Mechanics Semiclassical Vibrational Spectroscopy: The Case of Thymidine.

We introduce a quantum mechanics/molecular mechanics semiclassical method for studying the solvation process of molecules in water at the nuclear quantum mechanical level with atomistic detail. We employ it in vibrational spectroscopy calculations because this is a tool that is very sensitive to the molecular environment. Specifically, we look at the vibrational spectroscopy of thymidine in liquid water. We find that the C═O frequency red shift and the C═C frequency blue shift, experienced by thymidyne upon solvation, are mainly due to reciprocal polarization effects, that the molecule and the water solvent exert on each other, and nuclear zero-point energy effects. In general, this work provides an accurate and practical tool to study quantum vibrational spectroscopy in solution and condensed phase, incorporating high-level and computationally affordable descriptions of both electronic and nuclear problems.

Cholesky Decomposition-Based Implementation of Relativistic Two-Component Coupled-Cluster Methods for Medium-Sized Molecules.

A Cholesky decomposition (CD)-based implementation of relativistic two-component coupled-cluster (CC) and equation-of-motion CC (EOM-CC) methods using an exact two-component Hamiltonian augmented with atomic-mean-field spin-orbit integrals (the X2CAMF scheme) is reported. The present CD-based implementation of X2CAMF-CC and EOM-CC methods employs atomic-orbital-based algorithms to avoid the construction of two-electron integrals and intermediates involving three and four virtual indices. Our CD-based implementation extends the applicability of X2CAMF-CC and EOM-CC methods to medium-sized molecules with the possibility to correlate around 1000 spinors. Benchmark calculations for uranium-containing small molecules were performed to assess the dependence of the CC results on the Cholesky threshold. A Cholesky threshold of 10-4 is shown to be sufficient to maintain chemical accuracy. Example calculations to illustrate the capability of the CD-based relativistic CC methods are reported for the bond-dissociation energy of the uranium hexafluoride molecule, UF6, with up to quadruple-ζ basis sets, and the lowest excitation energy in the solvated uranyl ion [UO22+(H2O)12].

Heptazine, Cyclazine, and Related Compounds: Chemically-Accurate Estimates of the Inverted Singlet-Triplet Gap.

Molecules that violate Hund's rule and exhibit an inverted gap between the lowest singlet S1 and triplet T1 excited states have attracted considerable attention due to their potential applications in optoelectronics. Among these molecules, the triangular-shaped heptazine, and its derivatives, have been in the limelight. However, conflicting reports have arisen regarding the relative energies of S1 and T1. Here, we employ highly accurate levels of theory, such as CC3, to not only resolve the debate concerning the sign but also quantify the magnitude of the S1-T1 gap. We also determined the 0-0 energies to evaluate the significance of the vertical approximation. In addition, we compute reference S1-T1 gaps for a series of 10 related molecules. This enables us to benchmark lower-order methods for future applications in larger systems within the same family of compounds. This contribution can serve as a foundation for the design of triangular-shaped molecules with enhanced photophysical properties.

Linear Response Equations Revisited: A Simple and Efficient Iterative Algorithm.

We present an algorithm to solve the linear response equations for Hartree-Fock, Density Functional Theory, and the Multiconfigurational Self-Consistent Field method that is both simple and efficient. The algorithm makes use of the well-established symmetric and antisymmetric combinations of trial vectors but further orthogonalizes them with respect to the scalar product induced by the response matrix. This leads to a standard, symmetric block eigenvalue problem in the expansion subspace that can be solved by diagonalizing a symmetric, positive definite matrix half the size of the expansion space. Numerical tests showed that the algorithm is robust and stable.

A novel coupled-cluster singles and doubles implementation that combines the exploitation of point-group symmetry and Cholesky decomposition of the two-electron integrals.

A novel implementation of the coupled-cluster singles and doubles (CCSD) approach is presented that is specifically tailored for the treatment of large symmetric systems. It fully exploits Abelian point-group symmetry and the use of the Cholesky decomposition of the two-electron repulsion integrals. In accordance with modern CCSD algorithms, we propose two alternative strategies for the computation of the so-called particle-particle ladder term. The code is driven toward the optimal choice depending on the available hardware resources. As a large-scale application, we computed the frozen-core correlation energy of buckminsterfullerene (C60) with a polarized valence triple-zeta basis set (240 correlated electrons in 1740 orbitals).

A Quasi Time-Reversible Scheme Based on Density Matrix Extrapolation on the Grassmann Manifold for Born-Oppenheimer Molecular Dynamics.

This Letter introduces the so-called Quasi Time-Reversible scheme based on Grassmann extrapolation (QTR G-Ext) of density matrices for an accurate calculation of initial guesses in Born-Oppenheimer Molecular Dynamics (BOMD) simulations. The method shows excellent results on four large molecular systems that are representative of real-life production applications, ranging from 21 to 94 atoms simulated with Kohn-Sham (KS) density functional theory surrounded with a classical environment with 6k to 16k atoms. Namely, it clearly reduces the number of self-consistent field iterations while at the same time achieving energy-conserving simulations, resulting in a considerable speed-up of BOMD simulations even when tight convergence of the KS equations is required.

Assessing Implicit and Explicit Polarizable Solvation Models for Nuclear-Electronic Orbital Systems: Quantum Proton Polarization and Solvation Energetics.

Accurate simulations of many chemical processes require the inclusion of both nuclear quantum effects and a solvent environment. The nuclear-electronic orbital (NEO) approach, which treats electrons and select nuclei quantum mechanically on the same level, combined with a polarizable continuum model (PCM) for the solvent environment, addresses this challenge in a computationally practical manner. In this work, the NEO-PCM approach is extended beyond the IEF-PCM (integral equation formalism PCM) and C-PCM (conductor PCM) approaches to the SS(V)PE (surface and simulation of volume polarization for electrostatics) and ddCOSMO (domain decomposed conductor-like screening model) approaches. IEF-PCM, SS(V)PE, C-PCM, and ddCOSMO all exhibit similar solvation energies as well as comparable nuclear polarization within the NEO framework. The calculations show that the nuclear density does not leak out of the molecular cavity because it is much more localized than the electronic density. Finally, the polarization of quantized protons is analyzed in both continuum solvent and explicit solvent environments described by the polarizable MB-pol model, illustrating the impact of specific hydrogen-bonding interactions captured only by explicit solvation. These calculations highlight the relationship among solvation formalism, nuclear polarization, and energetics.

Fast Method for Excited-State Dynamics in Complex Systems and Its Application to the Photoactivation of a Blue Light Using Flavin Photoreceptor.

The excited-state dynamics of molecules embedded in complex (bio)matrices is still a challenging goal for quantum chemical models. Hybrid QM/MM models have proven to be an effective strategy, but an optimal combination of accuracy and computational cost still has to be found. Here, we present a method which combines the accuracy of a polarizable embedding QM/MM approach with the computational efficiency of an excited-state self-consistent field method. The newly implemented method is applied to the photoactivation of the blue-light-using flavin (BLUF) domain of the AppA protein. We show that the proton-coupled electron transfer (PCET) process suggested for other BLUF proteins is still valid also for AppA.

Coarse-Graining ddCOSMO through an Interface between Tinker and the ddX Library.

The domain decomposition conductor-like screening model is an efficient way to compute the solvation energy of solutes within a polarizable continuum medium in a linear scaling computational time. Despite its efficiency, the application to very large systems is still challenging. A possibility to further accelerate the algorithm is resorting to coarse-graining strategies. In this paper we present a preliminary interface between the molecular dynamics package Tinker and the ddX library. The interface was used to test a united atom coarse-graining strategy that allowed us to push ddCOSMO to its limits by computing solvation energies on systems with up to 7 million atoms. We first present benchmarks to find an optimal discretization, and then, we discuss the performance and results obtained with fine- and coarse-grained solvation energy calculations.

A Unique and Stable Polyproline I Helix Sorted out from Conformational Equilibrium by Solvent Polarity.

Polyproline I helical structures are often considered as the hidden face of their most famous geminal sibling, Polyproline II, as PPI is generally spotted only within a conformational equilibrium. We designed and synthesized a stable Polyproline I structure exploiting the striking tendency of (S)-indoline-2-carboxylic acid to drive the peptide bond conformation toward the cis amide isomer, when dissolved in polar solvents. The cooperative effect of only four amino acidic units is sufficient to form a preferential structure in solution. We shed light on this rare secondary structure with a thorough analysis of the spectroscopic and chiroptical properties of the tetramer, supported by X-ray crystallography and computational studies.

Trajectory Surface Hopping for a Polarizable Embedding QM/MM Formulation.

We present the implementation of trajectory surface-hopping nonadiabatic dynamics for a polarizable embedding QM/MM formulation. Time-dependent density functional theory was used at the quantum mechanical level of theory, whereas the molecular mechanics description involved the polarizable AMOEBA force field. This implementation has been obtained by integrating the surface-hopping program Newton-X NS with an interface between the Gaussian 16 and the Tinker suites of codes to calculate QM/AMOEBA energies and forces. The implementation has been tested on a photoinduced electron-driven proton-transfer reaction involving pyrimidine and a hydrogen-bonded water surrounded by a small cluster of water molecules and within a large water droplet.

Computation of NMR shieldings at the CASSCF level using gauge-including atomic orbitals and Cholesky decomposition.

We present an implementation of coupled-perturbed complete active space self-consistent field (CP-CASSCF) theory for the computation of nuclear magnetic resonance chemical shifts using gauge-including atomic orbitals and Cholesky decomposed two-electron integrals. The CP-CASSCF equations are solved using a direct algorithm where the magnetic Hessian matrix-vector product is expressed in terms of one-index transformed quantities. Numerical tests on systems with up to about 1300 basis functions provide information regarding both the computational efficiency and limitations of our implementation.