Bunching and Immobilization of Ionic Liquids in Nanoporous Metal–Organic Framework

Room-temperature ionic liquids (ILs) are a unique, novel class of designer solvents and materials with exclusive properties, attracting substantial attention in fields like energy storage and supercapacitors as well as in ion-based signal processing and electronics. For most applications, ILs need to be incorporated or embedded in solid materials like porous hosts. We investigate the dynamic structure of ILs embedded in well-defined pores of metal–organic frameworks (MOFs). The experimental data combined with molecular dynamics simulations unveil astonishing dynamic properties of the IL in the MOF nanoconfinement. At low IL loadings, the ions drift in the pores along the electric field, whereas at high IL loadings, collective field-induced interactions of the cations and anions lead to blocking the transport, thus suppressing the ionic mobility and tremendously decreasing the conductivity. The mutual pore blockage causes immobilized ions in the pores, resulting in a highly inhomogeneous IL density and bunched-up ions at the clogged pores. These results provide novel molecular-level insights into the dynamics of ILs in nanoconfinement, significantly enhancing the tunability of IL material properties

SSAGES : Software Suite for Advanced General Ensemble Simulations

Molecular simulation has emerged as an essential tool for modern-day research, but obtaining proper results and making reliable conclusions from simulations requires adequate sampling of the system under consideration. To this end, a variety of methods exist in the literature that can enhance sampling considerably, and increasingly sophisticated, effective algorithms continue to be developed at a rapid pace. Implementation of these techniques, however, can be challenging for experts and non-experts alike. There is a clear need for software that provides rapid, reliable, and easy access to a wide range of advanced sampling methods and that facilitates implementation of new techniques as they emerge. Here we present SSAGES, a publicly available Software Suite for Advanced General Ensemble Simulations designed to interface with multiple widely used molecular dynamics simulations packages. SSAGES allows facile application of a variety of enhanced sampling techniques—including adaptive biasing force, string methods, and forward flux sampling—that extract meaningful free energy and transition path data from all-atom and coarse-grained simulations. A noteworthy feature of SSAGES is a user-friendly framework that facilitates further development and implementation of new methods and collective variables. In this work, the use of SSAGES is illustrated in the context of simple representative applications involving distinct methods and different collective variables that are available in the current release of the suite. The code may be found at: https://github.com/MICCoM/SSAGES-public

Renewal events in glass-forming liquids

On cooling toward the glass transition temperature, glass-forming liquids display long periods of localized motion interrupted by fast “jumps” in the single-particle trajectories. Several theoretical models based on these single-particle jumps have been proposed, most prominently the continuous-time random walk (CTRW). The central assumption of the CTRW is that jumps are renewal events, i.e. that the internal clock of a particle can be reset upon a jump. In this paper, I present an easy-to-implement method to test whether jumps detected in a supercooled liquid or glass are renewal events or not. The test was applied to molecular dynamics simulations of a short-chain polymer melt, demonstrating that the jumps can in fact be treated as renewal events. The test further revealed that additional relaxation processes are present which are not accounted for in the CTRW picture, highlighting the limitations of this approach. The notion of renewal events in glass-forming systems could be a very important building block for the interpretation of aging and the glass transition. Furthermore, it could have practical implications for the study of non-equilibrium dynamics in glasses as well as mechanical rejuvenation

On the macrocyclization selectivity of meta-substituted diamines and dialdehydes: towards macrocycles with tunable functional peripheries

Abstract: The efficient preparation of functional rigid and soluble macrocycles remains a challenge for synthetic chemists. Here, we exploit the thermodynamic control of dynamic covalent chemistry to investigate the influence of the monomer structure on the macrocyclization selectivity. A series of rigid cyclic hexamer has been synthesized by imine condensation of benzene building blocks, i.e. meta-substituted diamines and dialdehydes, templated by calcium(II) chloride. The monomers were designed to feature various additional functional groups either available for further post-cyclization modifications or acting as solubilizing groups. The cyclization selectivity was systematically investigated and optimized depending on the length of the applied solubilizing group and on the nature of the additional functional group. A selectivity up to 92% was reached for the macrocyclization exhibiting trifluoromethyl and bromine groups at the outer periphery and hydroxyl groups in the cavity. Graphic abstract: [Figure not available: see fulltext.].</p

Efficient crystal structure prediction for structurally related molecules with accurate and transferable tailor-made force fields

Crystal structure prediction (CSP) has been historically used to complement experimental solid form screening and applied to individual molecules in drug development. The fast development of algorithms and computing resources offers the opportunity to use CSP earlier and for a broader range of applications in the drug design cycle. This study presents a novel paradigm of CSP specifically designed for structurally related molecules, referred to as Quick-CSP. The approach prioritizes more accurate physics through robust and transferable tailor-made force fields (TMFFs), such that significant efficiency gains are achieved through the reduction of expensive ab initio calculations. The accuracy of the TMFF is increased by the introduction of electrostatic multipoles and the fragment-based force field parameterization scheme is demonstrated to be transferable for a family of chemically related molecules. The protocol is benchmarked with structurally related compounds from the Bromodomain and Extraterminal (BET) domain inhibitors series. A new convergence criterion is introduced that aims at performing only as many ab initio optimizations of crystal structures as required to locate the bottom of the crystal energy landscape within a user-defined accuracy. The overall approach provides significant cost savings ranging from three to eight-fold less than the Full-CSP workflow. The reported advancements expand the scope and utility of the underlying CSP building blocks as well as their novel reassembly to other applications earlier in the drug design cycle to guide molecule design and selection

Predicting crystal form stability under real-world conditions

The physicochemical properties of molecular crystals, such as solubility, stability, compactability, melting behaviour and bioavailability, depend on their crystal form. In silico crystal form selection has recently come much closer to realization because of the development of accurate and affordable free-energy calculations. Here we redefine the state of the art, primarily by improving the accuracy of free-energy calculations, constructing a reliable experimental benchmark for solid–solid free-energy differences, quantifying statistical errors for the computed free energies and placing both hydrate crystal structures of different stoichiometries and anhydrate crystal structures on the same energy landscape, with defined error bars, as a function of temperature and relative humidity. The calculated free energies have standard errors of 1–2 kJ mol−1 for industrially relevant compounds, and the method to place crystal structures with different hydrate stoichiometries on the same energy landscape can be extended to other multi-component systems, including solvates. These contributions reduce the gap between the needs of the experimentalist and the capabilities of modern computational tools, transforming crystal structure prediction into a more reliable and actionable procedure that can be used in combination with experimental evidence to direct crystal form selection and establish control