In Silico Chemical Experiments in the Age of AI: From Quantum Chemistry to Machine Learning and Back.

Computational chemistry is an indispensable tool for understanding molecules and predicting chemical properties. However, traditional computational methods face significant challenges due to the difficulty of solving the Schrödinger equations and the increasing computational cost with the size of the molecular system. In response, there has been a surge of interest in leveraging artificial intelligence (AI) and machine learning (ML) techniques to in silico experiments. Integrating AI and ML into computational chemistry increases the scalability and speed of the exploration of chemical space. However, challenges remain, particularly regarding the reproducibility and transferability of ML models. This review highlights the evolution of ML in learning from, complementing, or replacing traditional computational chemistry for energy and property predictions. Starting from models trained entirely on numerical data, a journey set forth toward the ideal model incorporating or learning the physical laws of quantum mechanics. This paper also reviews existing computational methods and ML models and their intertwining, outlines a roadmap for future research, and identifies areas for improvement and innovation. Ultimately, the goal is to develop AI architectures capable of predicting accurate and transferable solutions to the Schrödinger equation, thereby revolutionizing in silico experiments within chemistry and materials science.

Generalization of the Tavis-Cummings model for multi-level anharmonic systems: Insights on the second excitation manifold.

Confined electromagnetic modes strongly couple to collective excitations in ensembles of quantum emitters, producing light-matter hybrid states known as polaritons. Under such conditions, the discrete multilevel spectrum of molecular systems offers an appealing playground for exploring multiphoton processes. This work contrasts predictions from the Tavis-Cummings model in which the material is a collection of two-level systems, with the implications of considering additional energy levels with harmonic and anharmonic structures. We discuss the exact eigenspectrum, up to the second excitation manifold, of an arbitrary number N of oscillators collectively coupled to a single cavity mode in the rotating-wave approximation. Elaborating on our group-theoretic approach [New J. Phys. 23, 063081 (2021)], we simplify the brute-force diagonalization of N2 × N2 Hamiltonians to the eigendecomposition of, at most, 4 × 4 matrices for arbitrary N. We thoroughly discuss the eigenstates and the consequences of weak and strong anharmonicities. Furthermore, we find resonant conditions between bipolaritons and anharmonic transitions where two-photon absorption can be enhanced. Finally, we conclude that energy shifts in the polaritonic states induced by anharmonicities become negligible for large N. Thus, calculations with a single or few quantum emitters qualitatively fail to represent the nonlinear optical response of the collective strong coupling regime. Our work highlights the rich physics of multilevel anharmonic systems coupled to cavities absent in standard models of quantum optics. We also provide concise tabulated expressions for eigenfrequencies and transition amplitudes, which should serve as a reference for future spectroscopic studies of molecular polaritons.

Driving chemical reactions with polariton condensates.

When molecular transitions strongly couple to photon modes, they form hybrid light-matter modes called polaritons. Collective vibrational strong coupling is a promising avenue for control of chemistry, but this can be deterred by the large number of quasi-degenerate dark modes. The macroscopic occupation of a single polariton mode by excitations, as observed in Bose-Einstein condensation, offers promise for overcoming this issue. Here we theoretically investigate the effect of vibrational polariton condensation on the kinetics of electron transfer processes. Compared with excitation with infrared laser sources, the vibrational polariton condensate changes the reaction yield significantly at room temperature due to additional channels with reduced activation barriers resulting from the large accumulation of energy in the lower polariton, and the many modes available for energy redistribution during the reaction. Our results offer tantalizing opportunities to use condensates for driving chemical reactions, kinetically bypassing usual constraints of fast intramolecular vibrational redistribution in condensed phase.

Nonequilibrium effects of cavity leakage and vibrational dissipation in thermally activated polariton chemistry.

In vibrational strong coupling (VSC), molecular vibrations strongly interact with the modes of an optical cavity to form hybrid light-matter states known as vibrational polaritons. Experiments show that the kinetics of thermally activated chemical reactions can be modified by VSC. Transition-state theory, which assumes that internal thermalization is fast compared to reactive transitions, has been unable to explain the observed findings. Here, we carry out kinetic simulations to understand how dissipative processes, namely, those introduced by VSC to the chemical system, affect reactions where internal thermalization and reactive transitions occur on similar timescales. Using the Marcus-Levich-Jortner type of electron transfer as a model reaction, we show that such dissipation can change reactivity by accelerating internal thermalization, thereby suppressing nonequilibrium effects that occur in the reaction outside the cavity. This phenomenon is attributed mainly to cavity decay (i.e., photon leakage), but a supporting role is played by the relaxation between polaritons and dark states. When nonequilibrium effects are already suppressed in the bare reaction (the reactive species are essentially at internal thermal equilibrium throughout the reaction), we find that reactivity does not change significantly under VSC. Connections are made between our results and experimental observations.

Computational method for highly constrained molecular dynamics of rigid bodies: Coarse-grained simulation of auxetic two-dimensional protein crystals.

The increasing number of protein-based metamaterials demands reliable and efficient theoretical and computational methods to study the physicochemical properties they may display. In this regard, we develop a simulation strategy based on Molecular Dynamics (MD) that addresses the geometric degrees of freedom of an auxetic two-dimensional protein crystal. This model consists of a network of impenetrable rigid squares linked through massless rigid rods. Our MD methodology extends the well-known protocols SHAKE and RATTLE to include highly non-linear holonomic and non-holonomic constraints, with an emphasis on collision detection and response between anisotropic rigid bodies. The presented method enables the simulation of long-time dynamics with reasonably large time steps. The data extracted from the simulations allow the characterization of the dynamical correlations featured by the protein subunits, which show a persistent motional interdependence across the array. On the other hand, non-holonomic constraints (collisions between subunits) increase the number of inhomogeneous deformations of the network, thus driving it away from an isotropic response. Our work provides the first long-timescale simulation of the dynamics of protein crystals and offers insights into promising mechanical properties afforded by these materials.

Polaritonic normal modes in transition state theory.

A series of experiments demonstrates that strong light-matter coupling between vibrational excitations in isotropic solutions of molecules and resonant infrared optical microcavity modes leads to modified thermally activated kinetics. However, Galego et al. [Phys. Rev. X 9, 021057 (2019)] recently demonstrated that, within transition state theory, effects of strong light-matter coupling with reactive modes are mostly electrostatic and essentially independent of light-matter resonance or even of the formation of vibrational polaritons. To analyze this puzzling theoretical result in further detail, we revisit it under a new light, invoking a normal mode analysis of the transition state and reactant configurations for an ensemble of an arbitrary number of molecules in a cavity, obtaining simple analytical expressions that produce similar conclusions as Feist. While these effects become relevant in optical microcavities if the molecular dipoles are anisotropically aligned, or in cavities with extreme confinement of the photon modes, they become negligible for isotropic solutions in microcavities. It is concluded that further studies are necessary to track the origin of the experimentally observed kinetics.

Correction: Polariton chemistry: controlling molecular dynamics with optical cavities.

[This corrects the article DOI: 10.1039/C8SC01043A.].

Resonant catalysis of thermally activated chemical reactions with vibrational polaritons.

Interaction between light and matter results in new quantum states whose energetics can modify chemical kinetics. In the regime of ensemble vibrational strong coupling (VSC), a macroscopic number [Formula: see text] of molecular transitions couple to each resonant cavity mode, yielding two hybrid light-matter (polariton) modes and a reservoir of [Formula: see text] dark states whose chemical dynamics are essentially those of the bare molecules. This fact is seemingly in opposition to the recently reported modification of thermally activated ground electronic state reactions under VSC. Here we provide a VSC Marcus-Levich-Jortner electron transfer model that potentially addresses this paradox: although entropy favors the transit through dark-state channels, the chemical kinetics can be dictated by a few polaritonic channels with smaller activation energies. The effects of catalytic VSC are maximal at light-matter resonance, in agreement with experimental observations.

Polariton chemistry: controlling molecular dynamics with optical cavities.

Molecular polaritons are the optical excitations which emerge when molecular transitions interact strongly with confined electromagnetic fields. Increasing interest in the hybrid molecular-photonic materials that host these excitations stems from recent observations of their novel and tunable chemistry. Some of the remarkable functionalities exhibited by polaritons include the ability to induce long-range excitation energy transfer, enhance charge conductivity, and inhibit or accelerate chemical reactions. In this review, we explain the effective theories of molecular polaritons which form a basis for the interpretation and guidance of experiments at the strong coupling limit. The theoretical discussion is illustrated with the analysis of innovative applications of strongly coupled molecular-photonic systems to chemical phenomena of fundamental importance to future technologies.

Etiopathogenesis of Burkitt's lymphoma: a lesson from a BL-like in CD1 mouse immune to Plasmodium yoelii yoelii.

INTRODUCTION: There is a jaw cancer that develops in children five to eight years old in holoendemic malaria regions of Africa, associated to malaria and Epstein Barr virus infections (EBV). This malignancy is known as endemic Burkitt's lymphoma, and histopatologically is characterized by a starry sky appearance. To date, no histopathologic expression of Burkitt's lymphoma has been reported in non-genetically manipulated experimental animals. The purpose of the study is to describe the case of a mouse immune to Plasmodium yoelii yoelii (Pyy) that developed a Burkitt's lymphoma-like neoplasm after repeated malaria infections. RESULTS: Immune mouse 10 (IM-10) developed neoplasms at eight months of age, after receiving three Pyy inoculations. At autopsy eight subcutaneous tumors were found of which the right iliac fosse tumor perforated the abdominal wall and invaded the colon. The histopathologic study showed that all neoplasms were malignant lymphomas of large non-cleaved cells also compatible with variants or previous states of development of a Burkitt's lymphoma-like. The thymus, however, showed a typical starry sky Burkitt's lymphoma-like neoplasm. CONCLUSIONS: Neoplasm development in CD1 mouse is associated to both, immunity against malaria and continuous antigenic stimulation with living parasites.It is the first observation of a histopathologically expressed Human Burkitt's lymphoma-like neoplasm in a non-genetically manipulated mouse.Chronic immune response associated to neoplasms development could probably be not an exclusive expression of malaria-host interaction but, it could be a pattern that can bee applied also to other agent-host interactions such as host-bacteria, fungus, virus and other parasites.

[Evaluation of Gastric Atrophy. Comparison between Sidney and OLGA Systems]. / Evaluación histopatológica de gastritis atrófica. Comparación de los sistemas Sidney y OLGA.

BACKGROUND: histopathologic identification of atrophy and metaplasia is decisive to stop the way of gastritis?carcinoma in patients with chronic gastritis. OBJECTIVE: to compare diagnostic concordance between Sidney system and the operative Link on Gastritis Assessment (OLGA) system. METHODS: 120 consecutive biopsies were analyzed by general pathologists according to the Sidney system. All of them were evaluated by a second pathologist who used OLGA System. We employed kappa index to evaluate diagnostic concordance between the classifications. RESULTS: the clinical picture includes dyspepsia (94 %), abdominal pain (50 %), gastroesophageal reflux (30 %), bleed of the upper digestive system (24 %), and presence of Helicobacter pylori (47.5 %). Four were diagnosed as atrophy by Sidney system and 26 cases with atrophy by OLGA system. The concordance between two classifications systems was too low (p = 0.05). CONCLUSIONS: the atrophy diagnosis, between systems, had low concordance. The description of metaplastic atrophy in the OLGA system represents the only one difference. The non-metaplastic atrophy is the same for both classifications. Therefore, the general pathologist should include this evaluation more consistently using OLGA system.

Amiloidosis cardiaca: hallazgos clinicopatológicos en 10 pacientes / Cardiac amyloidosis: clinical and pathologic report of 10 cases

Se presentan 10 casos con amiloidosis cardiaca obtenidos de una revisión de 12,000 autopsias realizadas en el Centro Médico Nacional La Raza, de 1975 a 1994. Cuatro fueron del sexo masculino y seis del femenino. La edad varió de 24 a 69 años (promedio 52.3 años). En siete casos fue primaria y en tres secundaria. En nueve sistémica y aislada en uno. El tiempo promedio del padecimiento fue de 2.9 meses. Como manifestaciones cardiacas se observó que 90 por ciento presentó insuficiencia cardiaca, 50 por ciento derrame pericárdico, 30 por ciento pleural, 20 por ciento soplo por insuficiencia mitral, 20 por ciento síncope y 20 por ciento angor pectoris; 70 por ciento presentaron datos de bajo voltaje y pobre progresión del primer vector de V1 a V3, 20 por ciento fibrilación ventricular y 20 por ciento bloqueo auriculoventricular. En 60 por ciento se encontraron diferentes grados de cardiomegalia y en todos se demostró la presencia de amiloide (promedio 424g); en 60 por ciento hipertrofia ventricular derecha, 50 por ciento en el ventrículo izquierdo y 50 por ciento bentricular; 30 por ciento músculos papilares, 20 por ciento trombo mural en aurícular izquierda, 50 por ciento lesión valvular y 30 por ciento arterias coronarias

Colestasis grave asociada a hipertiroidismo / Severe cholestasis associated to hypertiroidism

Se informa el caso de una mujer de 29 años de edad con enfermedad de Graves-Basedow, que se relacionó con colestasis centrolobulillar no atribuida a la insuficiencia cardiaca ni a la exposición a hepatotóxicos. Las bilirrubinas séricas totales alcanzaron cifras de 52 mg/dL, 889.2 µmol/L. Con el tratamiento de hipertiroidismo se corrigió la colestasis

Asociación del síndrome de Peutz Jeghers con dos carcinomas primarios: de intestino delgado y mama: informe de un paciente / Association of Peutz- Jeghers syndrome with 2 primary carcinomas: small intestine and breast: report of a patient

Se presenta el caso de un hombre de 54 años de edad que padece de Síndrome de Peutz Jeghers desde su infancia con las características clásicas de la enfermedad. Como adulto presentó cuadros de obstrución intestinal y hemorragia del tubo digestivo que fue abordada en su diagnóstico y manejo en múltiples formas incluyendo una resección intestinal masiva en 1958 por lo cual hasta la actualidad presenta complicaciones crónicas de intestino corto. En julio de 1985, posterior a una revisión clínica, se descubrió un nódulo mamario cuya biopsia mostró carcinoma por lo que se le sometió a una Mastectomía Radical. Un años después presentó un Adenocarcinoma de yeyuno que pudeo ser resecado quirúrgicamente. La asociación del SPJ con estas eventualidades por separado es alta, como lo muestra la revisión de la literatura que se realiza; sin embargo, la aparición de las 3 en conjunto ha sido informada solo en una ocasión prevía con SPJ como CA bilateral de mama y carcinoma duodenal en una mujer con SPJ. Este constituye al primer caso de la literatura mundial con las peculiaridades de ser hombre con CA de mama, portador de SPJ y CAS yeyunal. Este caso muestra en forma evidente las rutas biológicas del SPJ en su "diátesis neoplásica"

Ficomicosis: fisiopatogenia, variedades clínicas y causas / Phycomycosis: physiopathogenesis, clinical varieties and causes

Se presenta un caso de ficomicosis rinocerebral. La ficomicosis es una enfermedad invasiva por hongos oportunistas que ataca generalmente al huésped comprometido, en particular el paciente diabético con acidosis metabólica. Se informa el caso de una paciente de 25 años de edad que no se sabía diabética; hospitalizada por descompensación metabólica, desarrolló lesiones ulcerosas y edema en hemicara derecha, evolucionando con necrosis en dorso de nariz y manifestaciones clínicas de sistema nervioso central. Se hacen consideraciones acerca de la fisiopatología y formas clínicas más comunes de esta micosis y se revisa la literatura

Metamorfosis grasa aguda del embarazo: correlación anatomo clínica en ocho pacientes / Acute fatty metamorphoses of pregnancy: a clinical pathological correllation in 8 patients

De entre 10,406 autopsias efectuadas en el Centro Médico La Raza, IMSS de enero de 1959 a diciembre de 1984 se encontraron 7 casos de metamorfosis grasa aguda del embarazo (MGAE). Un sujeto más fue diagnosticado por biopsia hepática y la enferma sobrevive asintomática. Los datos clínicos más constantes fueron, ictericia, fiebre, dolor abdominal, hemorragia de aparato digestivo, insuficiencia renal y estado de coma. El diagnóstico debe tenerse en cuenta cuando en una mujer primigesta exista cuadro clínico de hepatitis fulminante. El tratamiento es sólo con cuidados intensivos de sostén

Mesenquimoma maligno con recidiva tardía como liposarcoma: presentación de un caso y revisión de la literatura / Malignant mesenchymoma with late recurrence as liposarcoma: report of a case and literature review

El mesenquimoma maligno es un tumor de tejidos blandos de origen mesenquimatoso, compuesto por células de dos o más estirpes no relacionadas; sus localizaciones más frecuentes son tejidos profundo de las extremidades inferiores, retroperitoneo, tórax y tejidos blandos de otras partes del cuerpo. Se presenta el caso de un paciente con un mesenquimoma retroperitoneal de gran tamaño (20 x 25 cm) tratado con resección amplia. El estudio histopatológico informó componentes de liposarcoma, osteosarcoma y condrosacorma. El tumor reapareció casi ocho años después, y se extirpó una tumoración de 10 x 12 cm con patrón histopatológico de liposarcoma. El enfermo está asintomático 24 meses después. El caso informado es de interés por tratarse de un mesenquimoma que recurre en una sola línea de diferenciación, comportamiento poco común de estos tumores, además de la buena evolución hasta la fecha de publicación sin terapéutica adyuvante