Equilibrium Structure Research Articles

"Freedom of design" in chemical compound space: towards rational in silico design of molecules with targeted quantum-mechanical properties.

The rational design of molecules with targeted quantum-mechanical (QM) properties requires an advanced understanding of the structure-property/property-property relationships (SPR/PPR) that exist across chemical compound space (CCS). In this work, we analyze these fundamental relationships in the sector of CCS spanned by small (primarily organic) molecules using the recently developed QM7-X dataset, a systematic, extensive, and tightly converged collection of 42 QM properties corresponding to ≈4.2M equilibrium and non-equilibrium molecular structures containing up to seven heavy/non-hydrogen atoms (including C, N, O, S, and Cl). By characterizing and enumerating progressively more complex manifolds of molecular property space-the corresponding high-dimensional space defined by the properties of each molecule in this sector of CCS-our analysis reveals that one has a substantial degree of flexibility or "freedom of design" when searching for a single molecule with a desired pair of properties or a set of distinct molecules sharing an array of properties. To explore how this intrinsic flexibility manifests in the molecular design process, we used multi-objective optimization to search for molecules with simultaneously large polarizabilities and HOMO-LUMO gaps; analysis of the resulting Pareto fronts identified non-trivial paths through CCS consisting of sequential structural and/or compositional changes that yield molecules with optimal combinations of these properties.

Equilibrium structure of a dense trimesic acid monolayer on a homogeneous solid surface: from atomistic simulation to thermodynamics.

A general methodology for determining the thermodynamic characteristics of rigid organic crystals on the atomistic level is presented. The proposed approach is based on a combination of grid interpolation of the precalculated intermolecular potential and kinetic Monte Carlo simulation of the gas-crystal system with an explicit interphase. The two-phase system is stabilized in a wide range of external parameters with an imposed external potential and damping field. The damping field reduces the intermolecular potential at the edges of the crystals and turns it off in the gas phase. To determine the thermodynamic characteristics of a crystal the conditions of equality of chemical potentials in coexisting phases are used. The intermolecular pairwise potential can be calculated on the atomistic or quantum level. In the kinetic Monte Carlo simulations, a grid interpolation of the precalculated potential is performed on each iteration of the algorithm. We have applied the approach to the thermodynamic analysis of a dense monolayer of trimesic acid on a homogeneous surface. The calculated free energy and entropy for the dense "superflower" and filled chicken-wire phases obey the Gibbs-Duhem equation, which confirms the thermodynamic consistency of our approach. Using the proposed approach, we have revealed that the dense "superflower" phase becomes metastable at zero pressure and 470-500 K. Under these conditions, the filled chicken-wire structure with partially released hexagonal cages is thermodynamically favourable. The proposed approach is a potentially universal tool for the thermodynamic analysis of crystals formed by "rigid" organic molecules of any complexity on the atomistic level.

Computational investigation of the phase behavior of colloidal squares with offset magnetic dipoles.

Colloidal particles with anisotropic shapes and interactions display rich phase behavior and have potential as structural bases for materials with controllable properties. In this paper, we explore the self-assembling characteristics of a new class of particles that have been shown experimentally to form reconfigurable structures: microscopic cube-shaped colloids with a magnetic dipole that is transversely offset from the particle's center of mass. We have performed in silico simulations of the dynamics of large numbers of dipolar squares in two-dimensions using discontinuous molecular dynamics (DMD). We use a coarse-grain method where the dipolar microcubes are represented by a group of four hard circles bonded together to create a rigid square in two-dimensions and two opposite charges are embedded within the square to represent a magnetic dipole. Annealing, or "slow-cooling", simulations are conducted to determine the equilibrium structures. Systems of dipolar squares tend to assemble into one of two different types of conformations: either single- or double-stranded assemblies, each with unique structures and phase diagrams in the temperature-density plane. Single-stranded assemblies form highly interconnected percolated, or gel-like, networks. In contrast, double stranded assemblies tend to form globally-aligned nematic states at high densities, although this is not seen consistently in all runs. The phase behavior of systems of dipolar squares depends not only on the system's temperature and density, but also on the type of dipole embedded within the square and on the relative number of squares with an opposite "handedness" that are present within the system.

Composition and temperature effects on the solution structure of SDS/octanol/brine by SANS, NMR and microscopy.

We investigate the solution structures of model sodium dodecyl sulfate/octanol/brine ternary mixtures across the lamellar (Lα), vesicle (L4) and micellar (L1) phases employing small angle neutron scattering (SANS), optical microscopy and nuclear magnetic resonance (NMR). Specifically, we examine the effect of co-surfactant octanol (0.2-9.48 w/v%) and temperature (25-65 °C) along dilution lines at fixed octanol : SDS ratios (0.08-1.21). A transition from Lα to sponge phase (L3) above 35 °C is found along the octanol : SDS = 1.21 isopleth, with phase coexistence above ϕ ≈ 0.14 weight fraction of surfactant and co-surfactant. The lamellar bilayers swell upon dilution, with an approximately linear increase of d-spacing, accompanied by a decrease of the Caillé parameter, indicative of greater membrane rigidity. At a lower octanol : SDS ratio of 0.62, coexistence of oblate micelles and vesicles is observed with preferential formation of vesicles at low concentrations. Dilution of the L1 phase, along octanol : SDS = 0.08, results in elongated micelles, as the NaCl : SDS ratio increases, while higher temperatures favour the formation of less elongated micelles. Our results provide a detailed map of the equilibrium structures found in the Lα vicinity of this extensively investigated flow-responsive surfactant system.

Mechanism and thermal effects of phytic acid-assisted porous carbon sheets for high-performance lithium–sulfur batteries

Optimized equilibrium structures of Li2Sn@PI/PCS900-P and (a) Li2Sn@PR/PCS900-P (b), and a schematic illustration of the accelerated nucleation and conversion of polysulphides by nitrogen and phosphorus atoms (c).

Pearlitic Morphologies Found in Carbon Steel Artefacts More than 2,000 Years Old

The results of this research reveal the possibility of observing another type of pearlite. Formed in archaeological steel pieces a few years old. Perlite resulting from diffusion over time at room temperature. For this we show the metallographic structure of archaeological samples that have remained buried in the soils of Roman Baetica for 2,000 years. Diffusion does not stop at a given moment but takes place, undoing structures that seemed to be stable; this diffusion produces new equilibrium structures that we cannot evaluate due to lack of time. The research was carried out as part of the Archaeological Analogues project for the Spanish National Nuclear Waste Company (ENRESA), revealing the alternation of structures of hot-worked and normalized carbon steels. The microscopy used is Scanning Electron Microscopy (SEM). The specimens, among many, two were selected because they have a good corrosion-free metallic core.

Calculation of the Proportion of Free Water Molecules in Aqueous Solutions Using the Parameters of Their Dielectric Permittivity in the Terahertz Range, Based on the Onsager Theory

The question of the structure of aqueous solutions is one of the most fundamental and complex, while it is relevant to all natural science disciplines. An important parameter of the dynamically equilibrium structure of an aqueous solution is the number of free water molecules. To date, there are no reliable and fully justified methods for determining this parameter. Recently, the terahertz time-domain spectroscopy (THz-TDS) method has been developing. It makes it possible to record the spectra of the complex permittivity in the THz region, where an orientation relaxation band of free water molecules is detected for aqueous solutions. The purpose of this work is to establish the relationship of the parameters of THz dielectric permittivity with the number of free water molecules. For this purpose, the process of polarization of water in the THz region was theoretically considered using the formalism of electrodynamics of continuous media. The Onsager theory is taken as a basis and its development is carried out for the case of high-frequency fields. As a result, an analytical ratio was obtained for calculating the proportion of free water molecules in solutions. A comparison with other well-known, more simplified and poorly substantiated approaches is presented. Calculations of the fraction of free molecules for a number of aqueous solutions have been carried out. It can be argued that the first theoretically justified approach to calculating the population of free water molecules in a solution, which does not contain internal contradictions, is presented.

Collective Variables for Crystallization Simulations-from Early Developments to Recent Advances.

Crystallization is an important physicochemical process which has relevance in material science, biology, and the environment. Decades of experimental and theoretical efforts have been made to understand this fundamental symmetry-breaking transition. While experiments provide equilibrium structures and shapes of crystals, they are limited to unraveling how molecules aggregate to form crystal nuclei that subsequently transform into bulk crystals. Computer simulations, mainly molecular dynamics (MD), can provide such microscopic details during the early stage of a crystallization event. Crystallization is a rare event that takes place in time scales much longer than a typical equilibrium MD simulation can sample. This inadequate sampling of the MD method can be easily circumvented by the use of enhanced sampling (ES) simulations. In most of the ES methods, the fluctuations of a system's slow degrees of freedom, called collective variables (CVs), are enhanced by applying a bias potential. This transforms the system from one state to the other within a short time scale. The most crucial part of such CV-based ES methods is to find suitable CVs, which often needs intuition and several trial-and-error optimization steps. Over the years, a plethora of CVs has been developed and applied in the study of crystallization. In this review, we provide a brief overview of CVs that have been developed and used in ES simulations to study crystallization from melt or solution. These CVs can be categorized mainly into four types: (i) spherical particle-based, (ii) molecular template-based, (iii) physical property-based, and (iv) CVs obtained from dimensionality reduction techniques. We present the context-based evolution of CVs, discuss the current challenges, and propose future directions to further develop effective CVs for the study of crystallization of complex systems.

Can kinetic hydrate inhibitors inhibit the growth of pre-formed gas hydrates?

Low dosage kinetic hydrate inhibitors (KHIs) are one of the most promising techniques for inhibition at the earliest stages of hydrate formation. Although KHI polymers are generally considered to inhibit nucleation, they also show powerful properties in terms of crystal growth inhibition. Some KHIs may even induce anomalous gas hydrate dissociation inside the hydrate stability zone depending on the conditions. While KHIs have been proven for both inhibition of hydrate nucleation and initial crystal growth, their performance when it comes to pre-formed hydrates – i.e. where significant hydrate has already formed prior to KHI injection/contact with the KHI – has yet to be investigated. In this work, the ability of PVCap polymer to inhibit pre-formed hydrates has been evaluated for a methane-water system. Results are consistent with KHIs being able to inhibit further hydrate growth where a considerable volume of hydrate is already present in the system prior to chemical injection. Not only that, but that in the case of the PVCap system studied here, injection can, under certain conditions, directly result in the partial to complete anomalous dissociation of all pre-formed hydrates, even though conditions are inside the hydrate region. It is speculated this behaviour is related to the transition from metastable to stable hydrate structures/phases; PVCap not preventing the dissociation (of unstable phases) step of this process but inhibiting subsequent regrowth of stable equilibrium structures.

Interfacial Layer Breaker: A Violation of Stokes’ Law in High-Speed Atomic Force Microscope Flows

Structured water near surfaces is important in nonclassical crystallization, biomineralization, and restructuring of cellular membranes. In addition to equilibrium structures, studied by atomic force microscopy (AFM), high-speed AFM (H-S AFM) can now detect piconewton forces in microseconds. With increasing speeds and decreasing tip diameters, there is a danger that continuum water models will not hold, and molecular dynamic (MD) simulations would be needed for accurate predictions. MD simulations, however, can only evolve over tens of nanoseconds due to memory and computational efficiency/speed limitations, so new methods are needed to bridge the gap. Here, we report a hybrid, multiscale simulation method, which can bridge the size and time scale gaps to existing experiments. Structured water is studied between a moving silica AFM colloidal tip and a cleaved mica surface. The computational domain includes 1,472,766 atoms. To mimic the effect of long-range hydrodynamic forces occurring in water, when moving the AFM tip at speeds from 5 × 10-7 to 30 m/s, a hybrid multiscale method with local atomistic resolution is used, which serves as an effective open-domain boundary condition. The multiscale simulation is thus equivalent to using a macroscopically large computational domain with equilibrium boundary conditions. Quantification of the drag force shows the breaking of continuum behavior. Nonmonotonic dependence on both the tip speed and distance from the surface implies breaking of the hydration layer around the moving tip at time scales smaller than water cluster formation and strong water compressibility effects at the highest speeds.

Extending the Pseudo-Phase Model of Detergent–Lipid Dispersions by a Detergent-Binding Protein

Mixed micellar drug delivery systems for poorly soluble active pharmaceutical ingredients (APIs) are easy to produce and long-term stable, because they represent equilibrium structures. However, their fate after intravenous injection is still largely unknown. Once injected into the bloodstream, they can potentially convert to vesicles or disappear altogether, with both API and excipients being picked up by blood components. Our study aimed at reducing the gap between the good, quantitative understanding of aqueous glycocholate (GC)-lecithin dispersions alone and the highly complex situation in the blood. To this end, we extended the pseudophase model previously established for lipid-detergent dispersions to include the detergent-binding protein albumin as another component. The model predicted a quaternary phase diagram with planar phase boundaries defined by key parameters of the ternary subsystems, which were then determined by isothermal titration calorimetry. They include the aqueous GC concentration upon bilayer-micelle coexistence, 5.2 mM, the GC-to-lipid mole ratios in coexisting bilayers (Resat = 0.2) and micelles (Resol = 0.7), as well as the capacity of the albumin to bind 0.1 GC molecules with a dissociation constant of KD = 0.1 mM and 6 GC molecules with KD = 0.7 mM. Subsequent measurements in the quaternary system showed phase boundaries in good agreement with the model predictions. In addition, the critical micelle concentration of GC shows a minimal value (midpoint of transition) of 9.1 mM at the temperature of 24 °C where the demicellization enthalpy is zero. The demicellization process is accompanied by a heat capacity change of 29 cal/mol K. The model improves the understanding of the mixed micellar drug delivery systems. The success of the approach encourages including even more blood components, like lipoproteins, to a quantitative treatment.

Dark Matter–admixed Rotating White Dwarfs as Peculiar Compact Objects

Discoveries of anomalous compact objects challenge our understanding of the standard theory of stellar structures and evolution, so they serve as an excellent laboratory for searching for new physics. Earlier studies on spherically symmetric dark matter (DM)–admixed compact stars could explain a handful of anomalies. In this paper, we investigate the observational signatures of DM-admixed rotating white dwarfs, and make connections to observed peculiar compact objects. We compute the equilibrium structures of DM-admixed rotating white dwarfs using a self-consistent, two-fluid method, with the DM component being a nonrotating degenerate Fermi gas. We find that admixing DM to rotating white dwarfs could: (1) account for some peculiar white dwarfs that do not follow their usual mass–radius relation; (2) allow stable rapid-rotating white dwarfs that are free from thermonuclear runaway to exist, which could explain some soft gamma-ray repeaters/anomalous X-ray pulsars; and (3) produce universal I (moment of inertia)–Love (tidal Love number)–Q (quadrupole moment) relations that span bands above those without DM admixture, thus providing an indirect way of searching for DM in white dwarfs through gravitational-wave detection. To conclude, DM-admixed rotating white dwarfs can account for some peculiar compact objects. Our results suggest a systematic approach to accounting for the unusual compact objects that upcoming surveys could discover.

Remodeling of the microbiota improves the environmental adaptability and disease resistance in Tibetan pigs.

The establishment of intestinal microbiota and the maintenance of its equilibrium structure plays an important role in Tibetan pigs during different growth stages. Understanding the structure and function of the intestinal microbiota at different growth stages of Tibetan pigs can provide a theoretical basis for guiding nutritional regulation and feeding management in different stages. Fecal samples were collected from the Tibetan piglets at different growth stages, and the 16S rRNA was sequenced to analyze the changes of intestinal microbiota. Alpha and Beta diversity indexes showed that the diversity of the intestinal microbiota did not change during the three growth stages, and the main components of intestinal microbiota were not significantly different. At the phylum level, Firmicutes and Bacteroidetes were dominant and abundant at different growth stages and were not restricted by age. At the genus level, Streptococcus, Lactobacillus, and Bifidobacterium were the most dominant in the TP10d and TP40d groups, Streptococcus was the most dominant in the TP100d group, followed by Treponema_2 and Lactobacillus. Fusobacteria, Gluconobacter, and Synergistetes were found to be specific genera of 10-day-old Tibetan piglets by LEfSe combined with LDA score. The change of diet made Tenericutes and Epsilonbacteraeota, which are closely related to digestive fiber, become specific bacteria at the age of 40 days. With the consumption of oxygen in the intestine, obligate anaerobes, such as Verrucomicrobia, Fibrobacter, and Planctomycetes, were the characteristic genera of 100 days. KEGG function prediction analysis showed that the intestinal microbiota function of Tibetan pigs changed dynamically with the growth and development of Tibetan piglets. In conclusion, the structure and composition of the intestinal microbiota of Tibetan pigs are significantly different at different growth and development stages, which plays an important role in their immune performance.

Digital Twins Solve the Mystery of Raman Spectra of Parental and Reduced Graphene Oxides.

Digital Twins concept presents a new trend in virtual material science, common to all computational techniques. Digital twins, virtual devices and intellectual products, presenting the main constituents of the concept, are considered in detail on the example of a complex problem, which concerns an amazing identity of the D-G-doublet Raman spectra of parental and reduced graphene oxides. Digital twins, presenting different aspects of the GO and rGO structure and properties, were virtually synthesized using a spin-density algorithm emerging from the Hartree-Fock approximation. Virtual device presents AM1 version of the semi-empirical unrestricted HF approximation. The equilibrium structure of the twins as well as virtual one-phonon harmonic spectra of IR absorption and Raman scattering constitute a set of intellectual products. It was established that in both cases the D-G doublets owe their origin to the sp3 and sp2 C-C stretchings, respectively. This outwardly similar community reveals different grounds. Thus, multilayer packing of individual rGO molecules in stacks provides the existence of the sp3 D band in addition to sp2 G one. The latter is related to stretchings of the main pool of sp2 C-C bonds, while the sp3 constituent presents out-of-plane stretchings of dynamically stimulated interlayer bonds. In the GO case, the sp3 D component, corresponding to stretchings of the main pool of sp3 C-C bonds, is accompanied by an sp2 G component, which is related to stretchings of the remaining sp2 C-C bonds provided with the spin-influenced prohibition of the 100% oxidative reaction in graphene domain basal plane.

Impact of counterion valency on the rheology of sulfonated cellulose nanocrystal hydrogels

A systematic rheological study on the influence of valency of different counterions on the properties of CNC hydrogels was carried out. Rheo-polarized microscopy was used to prove that preshear of 500 s−1 for 1 min is adequate to completely breakdown agglomerates in the suspension. Furthermore, a rest period of 30 min is sufficient to recover the equilibrium structure of hydrogels. Changing counterions from monovalent (Na+, K+, Li+), to divalent (Mg2+, Ca2+) and to trivalent (Al3+) influenced the network formation. CNC suspensions with monovalent counterions are isotropic at 3 wt%, anisotropic with chiral nematic structures at 5 wt% and form birefringent gels at 7 wt%. Conversely, divalent and trivalent counterions facilitate network formation, leading to gel like behavior at all concentrations. Sonication of CNC samples with monovalent counterions lowers the viscosity by two orders of magnitude while the opposite is true for multivalent counterions due to the formation of strong networks. The varying rheological properties displayed from CNCs with different counter ions may influence the use of CNC as rheological modifiers in fluid-based applications.

Intersystem Crossing Rates in Photoexcited Rose Bengal: Solvation versus Isolation.

We compare the intersystem crossing rate, kISC, of Rose Bengal (RB) in an aqueous pH 12 solution with the corresponding relaxation rates of four different RB-derived anion and dianion species isolated in the gas phase: the doubly deprotonated dianion ([RB-2H]2-), the singly deprotonated monoanion ([RB-H]-), and the corresponding singly negatively charged sodium and cesium adducts ([RB-2H + Na]- and [RB-2H + Cs]-, respectively). Each of them was probed following photoexcitation of their first singlet excited states (S1) at or near room temperature. The solution was studied by transient absorption spectroscopy, whereas the mass-selected anions were characterized by time-resolved photoelectron spectroscopy─all with ca. 50 femtosecond temporal resolution. [RB-H]- shows an S1 lifetime of ca. 80 ps; the solution ensemble, thought to consist primarily of solvated dianion chromophores, shows a similar lifetime of ca. 70 ps. By contrast, the isolated dianion, [RB-2H]2-, has a much longer lifetime. Superimposed on S1 decay attributable mainly to intersystem crossing, all four isolated anions also show some rapid oscillatory features of the transient photoelectron signal on a 4-5 ps timescale after excitation. Interestingly, an analogous phenomenon is also seen in the transient absorption measurements. We attribute it to a librational oscillation as the S1 state, initially populated in the S0 geometry, relaxes into its excited state equilibrium structure. Some implications of these observations for RB photophysics and interpretation of solution measurements are discussed─also in terms of density functional theory and time-dependent density functional theory calculations of ground and excited states.

Insights into the equilibrium structure and translocation mechanism of TP1, a spontaneous membrane-translocating peptide

Crossing the cellular membrane is one of the main barriers during drug discovery; many potential drugs are rejected for their inability to integrate into the intracell fluid. Although many solutions have been proposed to overcome this barrier, arguably the most promising solution is the use of cell-penetrating peptides. Recently, an array of hydrophobic penetrating peptides was discovered via high throughput screening which proved to be able to cross the membrane passively, and although these peptides proved to be effective at penetrating the cell, the details behind the underlying mechanism of this process remain unknown. In this study, we developed a method to find the equilibrium structure at the transmembrane domain of TP1, a hydrophobic penetrating peptide. In this method, we selectively deuterium-label amino acids in the peptidic chain, and employ results of ^2H-NMR spectroscopy to find a molecular dynamics simulation of the peptide that reproduces the experimental results. Effectively finding the equilibrium orientation and dynamics of the peptide in the membrane. We employed this equilibrium structure to simulate the entire translocation mechanism and found that after the peptide reaches its equilibrium structure, it must undergo a two-step mechanism in order to completely translocate the membrane, each step involving the flip-flop of each arginine residue in the peptide. This leads us to conclude that the RLLR motif is essential for the translocating activity of the peptide.

An interesting case of symmetry breaking in the absence of symmetry: the bicarbonate radical (HCO3)

As part of a computational study of the thermochemical properties of systems related to carbonic acid (HCO), an interesting phenomenon was observed in the bicarbonate radical (HCO). This species belongs to the class of formoxyl radicals, but lacks the geometric symmetry of the more heavily-studied and prototypical HCO and FCO molecules. However, it is not immune from the problems that those molecules present to electronic structure calculations. Specifically, at geometries in the vicinity of the equilibrium structure, three solutions to the unrestricted Hartree-Fock equations can be found: two in which the unpaired spin is largely localized onto one of the (inequivalent) carbonyl oxygen atoms, and one in which the spin is delocalized. While all three of these reference functions comprise orbitals that transform as pure irreducible representations of the point group, the two localized choices qualitatively correspond to the symmetry-broken solution of the formoxyl species and the delocalized solution qualitatively corresponds to the symmetry-preserving (but orbitally unstable) solution. The three solutions are described in this work, as well as the corresponding ambiguities that result in the thermochemical characterization of this species.

Experimental investigation and thermodynamic assessment of the Al–Ag–Sc system

As an important system in heat-resistant aluminium alloys, Al–Ag–Sc still has no publication on the investigation of thermodynamics and phase equilibria. In the present work, the isothermal sections of the Al–Ag–Sc ternary system at 500 and 600 ºC were experimentally measured through electron probe microanalysis (EPMA) and X-ray diffraction (XRD) for alloy samples. The ternary maximum solubility of Al in AgSc, Ag2Sc, Ag4Sc, and Ag in Al3Sc are 20.5 ± 0.5, 5.2 ± 0.3, 6.3 ± 0.2 and 12.5 ± 0.3 at%, respectively. In addition, two stable ternary compounds Al36Sc36Ag28 and Al27Sc18Ag55 were newly discovered. The solidification paths were measured for as-cast alloys. Five primary phases AgSc, (Ag), Ag2AlSc, Al36Sc36Ag28 and Al3Sc were revealed. The end-members formation enthalpies of the Al–Ag–Sc intermetallic compounds were computed by first-principles calculations. Based on the experimental and first-principles calculations results, a set of thermodynamic parameters for the Al–Ag–Sc system were established by the application of the CALPHAD (CALculation of PHAse Diagrams) method. The phase equilibrium, isothermal section, liquidus projection and solidification structure are well reproduced by using the thermodynamic parameters obtained in this work.

Scale-free-modeling (harmonic) vibrational frequencies: Assessing accuracy and cost-effectiveness by CBS extrapolation.

Empirical scaling of calculated vibrational harmonic frequencies is a popular approach used in the field of molecular sciences. A nonempirical scheme that aims at reducing their basis set error is suggested here. Nearly as cost-effective as the scaled Kohn-Sham density functional theory (KS DFT), it consists of splitting the frequencies into Hartree-Fock and electron correlation contributions, followed by their extrapolation to the complete basis set (CBS) limit. Since the former converges exponentially, the overall cost may actually equal that of CBS extrapolation of the correlation part. Despite shifts in the molecular geometry during vibration, reasons are advanced to justify the approach, with extrapolation from the first two steps of the basis set ladder being effective in accelerating convergence. As benchmark data, a set of harmonic frequencies and zero-point energies for 15 molecules is employed at the second-order Moller-Plesset and coupled-cluster single double triple [CCSD(T)] levels of theory. The results outperform the optimized KS DFT scaled values. As a second test set, equilibrium structures and harmonic frequencies were computed for H2O2, CH2NH, C2H2O, and the trans-isomer of 1,2-C2H2F2. The results are also encouraging, particularly when improved for excess correlation at the CCSD(T)/VDZ level via the focal-point approach. In extreme cases, CBS extrapolation is done from two double-ζ calculations: one canonical and the other using explicit correlation theory. As a further case study, benzene is considered. While the CCSD(T) results show the smallest deviation from the best estimates, the MP2 results also attain good quality: When improved for excess correlation, they show 6-10cm-1 errors relative to the best data, only slightly outperformed at the CCSD(T)/CBS level. Tentative results for the fundamental frequencies are also presented.