Noncovalent Systems Research Articles

Toward a less costly but accurate calculation of the CCSD(T)/CBS noncovalent interaction energy

The popular method of calculating the noncovalent interaction energies at the coupled-cluster single-, double-, and perturbative triple-excitations [CCSD(T)] theory level in the complete basis set (CBS) limit was to add a CCSD(T) correction term to the CBS second-order Møller-Plesset perturbation theory (MP2). The CCSD(T) correction term is the difference between the CCSD(T) and MP2 interaction energies evaluated in a medium basis set. However, the CCSD(T) calculations with the medium basis sets are still very expensive for systems with more than 30 atoms. Comparatively, the domain-based local pair natural orbital coupled-cluster method [DLPNO-CCSD(T)] can be applied to large systems with over 1,000 atoms. Considering both the computational accuracy and efficiency, in this work, we propose a new scheme to calculate the CCSD(T)/CBS interaction energies. In this scheme, the MP2/CBS term keeps intact and the CCSD(T) correction term is replaced by a DLPNO-CCSD(T) correction term which is the difference between the DLPNO-CCSD(T) and DLPNO-MP2 interaction energies evaluated in a medium basis set. The interaction energies of the noncovalent systems in the S22, HSG, HBC6, NBC10, and S66 databases were recalculated employing this new scheme. The consistent and tight settings of the truncation parameters for DLPNO-CCSD(T) and DLPNO-MP2 in this noncanonical CCSD(T)/CBS calculations lead to the maximum absolute deviation and root-mean-square deviation from the canonical CCSD(T)/CBS interaction energies of less than or equal to 0.28 kcal/mol and 0.09 kcal/mol, respectively. The high accuracy and low cost of this new computational scheme make it an excellent candidate for the study of large noncovalent systems.

Fractional Charge by Fixed-Node Diffusion MonteCarlo Method.

Fixed-node diffusion MonteCarlo (FNDMC) method is a stochastic quantum many-body approach that has a great potential in electronic structure theory. We examine how FNDMC total energy E(N) satisfies exact constraints, linearity and derivative discontinuity, versus fractional electron number N, if combined with mean-field trial wave functions that miss such features. H and Cl atoms with fractional charge reveal that FNDMC method is well able to restore the piecewise linearity of E(N). The method uses ensemble and projector ingredients to achieve the correct charge localization. A water-solvated Cl^{-} complex illustrates superior performance of FNDMC method for charged noncovalent systems.

Thermoresponsive and Covalently Cross-Linkable Hydrogels for Intra-Articular Drug Delivery.

The local delivery of drugs to joints is a recognized strategy in the treatment of osteoarthritis. Hydrogels, particularly those that can be injected as liquids but undergo gelation in the joint, are promising platforms for intra-articular drug delivery. However, their properties must be carefully designed and tuned to achieve sustained drug release, which has been a challenge with previous hydrogels. We describe here the use of a combination of noncovalent thermal gelation and covalent cross-linking with poly(caprolactone-co-lactide)(PCLA)-poly(ethylene glycol)(PEG)-PCLA triblock copolymers to achieve hydrogels with sustained drug release in joints. The hybrid cross-linking approach afforded higher viscoelastic and compression moduli compared to noncovalent cross-linking alone and enabled celecoxib as well as other drugs to be loaded without substantially compromising the mechanical properties. Celecoxib release in vitro was much slower for the hybrid cross-linked hydrogel, with only 20% released over 22 days, compared to 90% released over 22 days for a noncovalently cross-linked hydrogel. Furthermore, the burst release of celecoxib was reduced in vivo in horse joints compared to noncovalent systems, and the drug was detected in synovial fluid for a period of two months. Overall, this new hydrogel system shows significant promise as a platform for further development in intra-articular delivery.

Toward Accurate Hydrogen Bonds by Scalable Quantum Monte Carlo.

Single-determinant (SD) fixed-node diffusion Monte Carlo (FNDMC) gains popularity as a benchmark method scalable to large noncovalent systems, although its accuracy limits are not yet fully mapped out. We report on an interesting example of significant SD FNDMC accuracy variations in middle-sized hydrogen-bonded dimer complexes, formic acid (FA) vs methanediol (MD), distinct by the maximum bond order (2 vs 1). While the traditional SD FNDMC schemes based on bias cancellation are capable of achieving benchmark (2%) accuracy for MD, this has not been the case for FA. We identify the leading systematic error source in energy differences and show that suitably designed Jastrow factors enable SD FNDMC to reach the reference accuracy for FA. This work clearly illustrates the varying accuracy of the present-day SD FNDMC at the 0.1 kcal/mol scale for a particular set of systems but also points out promising routes toward alleviation of these shortcomings, still within the single-reference framework.

Small Basis Set Allowing the Recovery of Dispersion Interactions with Double-Hybrid Functionals.

Taking advantage of the compensation between Basis Set Superposition Error and Basis Set Incompleteness Error, a new basis is developed to improve the performances of Double Hybrid (DH) functionals in reproducing interaction energies in weak noncovalent systems. Using a self-consistent formula, containing only energy terms computed for dimers and the corresponding monomers at the same level of theory, the exponents of the more external functions of the Def2-SVPD basis were optimized on three systems extracted from the S22 set. The transferability of the obtained basis set, called DH-SVPD, was then tested on five benchmark sets, and it is assessed by considering six DH functionals, eventually corrected with empirical dispersion corrections (for a total of 16 methods). Our results show that this simple approach is able to provide accurate results for noncovalent interaction energies of all the considered systems, and, in particular, to recover the performances obtained by coupling the DH functionals with empirical dispersion corrections.

Hybrid Nanoparticle Platform for Nanoscale Scintillation Proximity Assay.

β-particle emitting radionuclides, such as 3H, 14C, 32P, 33P, and 35S, are important molecular labels due to their small size and the prevalence of these atoms in biomolecules but are challenging to selectively detect and quantify within aqueous biological samples and systems. Here, we present a core-shell nanoparticle-based scintillation proximity assay platform (nanoSPA) for the separation-free, selective detection of radiolabeled analytes. nanoSPA is prepared by incorporating scintillant fluorophores into polystyrene core particles and encapsulating the scintillant-doped cores within functionalized silica shells. The functionalized surface enables covalent attachment of specific binding moieties such as small molecules, proteins, or DNA that can be used for analyte-specific detection. nanoSPA was demonstrated for detection of 3H-labeled analytes, the most difficult biologically relevant β-emitter to measure due to the low energy β-particle emission, using three model assays that represent covalent and non-covalent binding systems that necessitate selectivity over competing 3H-labeled species. In each model, nmol quantities of target were detected directly in aqueous solution without separation from unbound 3H-labeled analyte. The nanoSPA platform facilitated measurement of 3H-labeled analytes directly in bulk aqueous samples without surfactants or other agents used to aid particle dispersal. Selectivity for bound 3H-analytes over unbound 3H analytes was enhanced up to 30-fold when the labeled species was covalently bound to nanoSPA, and 4- and 8-fold for two non-covalent binding assays using nanoSPA. The small size and enhanced selectivity of nanoSPA should enable new applications compared to the commonly used microSPA platform, including the potential for separation-free, analyte-specific cellular or intracellular detection.

Emerging Design Principles for Enhanced Solar Energy Utilization with Singlet Fission

Singlet fission (SF), the generation of two triplet excitons per the absorption of one photon, is a promising strategy for increasing the efficiency of solar cells beyond the theoretical Shockley–Queisser limit of 34%. Upon photon absorption by a SF molecule, the initially created singlet excited state (S1) interacts with a neighboring chromophore and is first transformed into a triplet pair (TT), which can be subsequently separated into independent triplet excitons (2T1). These independent triplet excitons can be harvested through triplet charge extraction or triplet energy transfer to an acceptor. Research on SF systems has revealed rates and efficiencies of triplet formation and triplet pair decorrelation that are strongly dependent on interchromophore coupling, which is dictated by molecular structure and the resulting geometrical arrangement of chromophores adopted in covalent (e.g., dimers) and noncovalent (e.g., films and crystals) systems. Incorporation of SF materials into realistic device archit...

Photoinduced electron transfer in non-covalent free-base octaethylporphyrin and 2-nitrofluorene donor-acceptor system: A combined experimental and quantum chemical study

Photosynthetic reaction center functions through non-covalent incorporation into a well-defined transmembrane proteins. In the context of exploring photoinduced electron transfer (PET) in non-covalent donor-acceptor systems, we have investigated electron transfer from free-base octaethylporphyrin (OEP) donor to 2-nitrofluorene (2NF) acceptor in acetonitrile (ACN), a polar solvent. Steady-state and time-resolved emission spectroscopic studies in conjunction with density functional theory (DFT) calculations were employed to explore the electron transfer process. Quenching of the fluorescence emission intensity as well as fluorescence lifetime of the OEP upon excitation at the Q band of OEP at 300 K, is attributed to the PET from OEP to 2NF. Our DFT [wB97XD functional and 6-31G (d,p) basis set] calculations also support the interaction between donor and acceptor and also reveals the co-facial π-π interaction energy of −24.6 kcal/mol with intermolecular distance <4 Å. Our results are expected to shed light on PET in non-covalent donor acceptor systems.

Electron density learning of non-covalent systems.

Chemists continuously harvest the power of non-covalent interactions to control phenomena in both the micro- and macroscopic worlds. From the quantum chemical perspective, the strategies essentially rely upon an in-depth understanding of the physical origin of these interactions, the quantification of their magnitude and their visualization in real-space. The total electron density ρ(r) represents the simplest yet most comprehensive piece of information available for fully characterizing bonding patterns and non-covalent interactions. The charge density of a molecule can be computed by solving the Schrödinger equation, but this approach becomes rapidly demanding if the electron density has to be evaluated for thousands of different molecules or very large chemical systems, such as peptides and proteins. Here we present a transferable and scalable machine-learning model capable of predicting the total electron density directly from the atomic coordinates. The regression model is used to access qualitative and quantitative insights beyond the underlying ρ(r) in a diverse ensemble of sidechain–sidechain dimers extracted from the BioFragment database (BFDb). The transferability of the model to more complex chemical systems is demonstrated by predicting and analyzing the electron density of a collection of 8 polypeptides.

Novel non-covalent supramolecular systems based on zinc(II) bis(dipyrromethenate)s with fullerenes

This paper presents the results of UV/vis, fluorescence, FT-IR, DOSY, and DFT study of a novel non-covalent supramolecular systems based on zinc(II) bis(dipyrromethenate)s ([Zn2L2]) with C60. It was found that zinc(II) bis(dipyrromethenate) forms stable supramolecular π-π-complexes ([Zn2L2(C60)4]) with C60. DFT calculations revealed stable complexation between [Zn2L2] and C60. The [Zn2L2(C60)4] LUMO energy levels are predominantly spread on the C60 unit and the HOMO energy levels are mainly spread on the [Zn2L2]. The photoinduced electron transfer testing by the substantial fluorescence quenching of the [Zn2L2] by non-covalent bonded C60 gives the positive result that shows prospects of the studying [Zn2L2(C60)4] as the active layers in solar energy conversion devices.

Liquid Native MALDI Mass Spectrometry for the Detection of Protein-Protein Complexes

Native mass spectrometry (MS) encompasses methods to keep noncovalent interactions of biomolecular complexes intact in the gas phase throughout the instrument and to measure the mass-to-charge ratios of supramolecular complexes directly in the mass spectrometer. Electrospray ionization (ESI) in nondenaturing conditions is now an established method to characterize noncovalent systems. Matrix-assisted laser desorption/ionization (MALDI), on the other hand, consumes low quantities of samples and largely tolerates contaminants, making it a priori attractive for native MS. However, so-called native MALDI approaches have so far been based on solid deposits, where the rapid transition of the sample through a solid state can engender the loss of native conformations. Here we present a new method for native MS based on liquid deposits and MALDI ionization, unambiguously detecting intact noncovalent protein complexes by direct desorption from a liquid spot for the first time. To control for aggregation, we worked with HUαβ, a heterodimer that does not spontaneously rearrange into homodimers in solution. Screening through numerous matrix solutions to observe first the monomeric protein, then the dimer complex, we settled on a nondenaturing binary matrix solution composed of acidic and basic organic matrices in glycerol, which is stable in vacuo. The role of temporal and spatial laser irradiation patterns was found to be critical. Both a protein-protein and a protein-ligand complex could be observed free of aggregation. To minimize gas-phase dissociation, source parameters were optimized to achieve a conservation of complexes above 50% for both systems.Graphical ᅟ

Architectonics: Design of Molecular Architecture for Functional Applications.

The term architectonics has its roots in the architectural and philosophical (as early as 1600s) literature that refers to "the theory of structure" and "the structure of theory", respectively. The concept of architectonics has been adapted to advance the field of molecular self-assembly and termed as molecular architectonics. In essence, the methodology of organizing molecular units in the required and controlled configurations to develop advanced functional systems for materials and biological applications comprises the field of molecular architectonics. This concept of designing noncovalent systems enables to focus on different functional aspects of designer molecules for biological and nonbiological applications and also strengthens our efforts toward the mastery over the art of controlled molecular self-assemblies. Programming complex molecular interactions and assemblies for specific functions has been one of the most challenging tasks in the modern era. Meticulously ordered molecular assemblies can impart remarkable developments in several areas spanning energy, health, and environment. For example, the well-defined nano-, micro-, and macroarchitectures of functional molecules with specific molecular ordering possess potential applications in flexible electronics, photovoltaics, photonic crystals, microreactors, sensors, drug delivery, biomedicine, and superhydrophobic coatings, among others. The functional molecular architectures having unparalleled properties are widely evident in various designs of Nature. By drawing inspirations from Nature, intended molecular architectures can be designed and developed to harvest various functions, as there is an inexhaustible resource and scope. In this Account, we present exquisite designer molecules developed by our group and others with an objective to master the art of molecular recognition and self-assembly for functional applications. We demonstrate the tailor-ability of molecular self-assemblies by employing biomolecules like amino acids and nucleobases as auxiliaries. Naphthalenediimide (NDI), perylenediimide (PDI), and few other molecular systems serve as functional modules. The effects of stereochemistry and minute structural modifications in the molecular designs on the supramolecular interactions, and construction of self-assembled zero-dimensional (OD), one-dimensional (1D), and two-dimensional (2D) nano- and microarchitectures like particles, spheres, cups, bowls, fibers, belts, helical belts, supercoiled helices, sheets, fractals, and honeycomb-like arrays are discussed in extensive detail. Additionally, we present molecular systems that showcase the elegant designs of coassembly, templated assembly, hierarchical assembly, transient self-assembly, chiral denaturation, retentive helical memory, self-replication, supramolecular regulation, supramolecular speciation, supernon linearity, dynamic pathway complexity, supramolecular heterojunction, living supramolecular polymerization, and molecular machines. Finally, we describe the molecular engineering principles learnt over the years that have led to several applications, namely, organic electronics, self-cleaning, high-mechanical strength, and tissue engineering.

Synthetic routes to nanomaterials containing anthracyclines: noncovalent systems.

Chemotherapy still constitutes a basic treatment for various types of cancer. Anthracyclines are effective antineoplastic drugs that are widely used in clinical practice. Unfortunately, they are characterized by high systemic toxicity and lack of tumour selectivity. A promising way to enhance treatment effectiveness and reduce toxicity is the synthesis of systems containing anthracyclines either in the form of complexes for the encapsulation of active drugs or their covalent conjugates with inert carriers. In this respect nanotechnology offers an extensive spectrum of possible solutions. In this review, we discuss recent advances in the development of anthracycline prodrugs based on nanocarriers such as copolymers, lipids, DNA, and inorganic systems. The review focuses on the chemical architecture of the noncovalent nanocarrier-drug systems.

Non-covalent interactions between thio-caffeine derivatives and water-soluble porphyrin in ethanol-water environment

To determine the binding interactions and ability to form the non-covalent systems, the association process between 5,10,15,20-tetrakis[4-(trimethylammonio)phenyl]-21H,23H-porphine tetra-p-tosylate (H2TTMePP) and a series of five structurally diverse thio-caffeine analogues has been studied in ethanol and ethanol-water solutions, analyzing its absorption and steady-state fluorescence spectra. The porphyrin fluorescence lifetimes in the systems studied were established as well. During the titration with thio-caffeine compounds the slight bathochromic effect and considerable hypochromicity of the porphyrin Soret band maximum can be noted. The fluorescence quenching effect observed for interactions in H2TTMePP - thio-caffeine derivative systems, as well as the order of binding and fluorescence quenching constants (of 105–103mol−1) suggest the existence of the mechanism of static quenching due to the formation of non-covalent and non-fluorescent stacking complexes. In all the systems studied the phenomenon of the fractional accessibility of the fluorophore for the quencher was observed as well. Additionally, the specific binding interactions, due to the changes in reaction environment polarity, can be observed. It was found that thio-caffeine compounds can quench the porphyrin fluorescence according to the structure of thio-substituent in caffeine molecule. The obtained results can be potentially useful from scientific, therapeutic or environmental points of view.

DSD-PBEP86-NL and DOD-PBEP86-NL functionals for noncovalent interactions: Basis set effects and tentative applications to large noncovalent systems

Basis set effects on the DSD-PBEP86-NL and DOD-PBEP86-NL functionals for noncovalent interactions have been extensively studied in this work. The cc-pVXZ (X = D, T, Q, 5, 6) and augmented aug-cc-pVXZ (X = D, T, Q) basis sets are systematically tested without counterpoise (CP) corrections against the well-known S66 database. Additionally, the basis sets of def2-TZVPP and def2-TZVPPD are also examined. Based on our computations, the performances of the aug-cc-pVQZ, cc-pV5Z, and cc-pV6Z basis sets are very approximate to those obtained with the def2-QZVP basis set for both the DSD-PBEP86-NL and DOD-PBEP86-NL functionals. Note that the short-range attenuation parameters for these two functionals were directly optimized using the def2-QZVP basis set without CP corrections against the S66 database. Generally speaking, the cc-pVXZ (X = D, T, Q), aug-cc-pVXZ (X = D, T, Q), def2-TZVPP, and def2-TZVPPD basis sets favor half CP correction for these two functionals. Nevertheless, the aug-cc-pVQZ basis set already performs well without any CP correction, especially for the DOD-PBEP86-NL functional. With respect to accuracy and computational cost, the cc-pVTZ and def2-TZVPP basis sets with half CP corrections are recommended for these two functionals to evaluate interaction energies of large noncovalent complexes.

Accurate calculations of the noncovalent systems with flat potential energy surfaces: Naphthalene dimer and azulene dimer

It is very challenging to construct the potential energy surfaces for the medium and large noncovalent systems employing the coupled clusters with singles, doubles, and perturbative triples, CCSD(T), at the complete basis set (CBS) limit. The main obstacle lies in the time-consuming and expensive CCSD(T) optimizations of the geometries. One method to overcome the obstacle is to use the cheap density functional theory with the D3 dispersion correction (DFT-D3) instead of the CCSD(T) method to optimize the geometries of the noncovalent systems. In the present study, the potential energy surfaces of the naphthalene dimer and azulene dimer were investigated using a combined DFT-D3 optimization and single-point CCSD(T)/CBS energy calculation scheme. The results clearly show that this scheme can give highly accurate CCSD(T)/CBS potential energy surfaces for the naphthalene dimer and the azulene dimer.

Empirical D3 Dispersion as a Replacement for ab Initio Dispersion Terms in Density Functional Theory-Based Symmetry-Adapted Perturbation Theory.

In density functional theory-based symmetry-adapted perturbation theory (DFT-SAPT) interaction energy calculations, the most demanding step is the calculation of the London dispersion term. For this bottleneck to be avoided and DFT-SAPT to be made applicable to larger systems, the ab initio dispersion terms can be replaced by one calculated empirically at an almost negligible cost ( J. Phys. Chem. A 2011 ; 115 , 11321 - 11330 ). We present an update of this approach that improves accuracy and makes the method applicable to a wider range of systems. It is based on Grimme's D3 dispersion correction for DFT, where the damping function is changed to one suitable for the calculation of the complete dispersion energy. The best results have been achieved with the Tang-Toennies damping function. It has been parametrized on the S66×8 data set for which we report density fitting DFT-SAPT/aug-cc-pVTZ interaction energy decomposition. The method has been validated on a diverse set of noncovalent systems including difficult cases such as very compact noncovalent complexes of charge-transfer type. The root-mean-square errors in the complete test set are 0.73 and 0.42 kcal mol-1 when charge-transfer complexes are excluded. The proposed empirical dispersion terms can also be used outside the DFT-SAPT framework, e.g., for the estimation of the amount of dispersion in a calculation where only the total interaction energy is known.

Novel non-covalent stable supramolecular ternary system comprising of cyclodextrin and branched polyethylenimine

The synthesis of a novel supramolecular system comprising of branched polyethylenimine and cyclodextrin, is presented. The synthesis route is based on the self-assembly phenomena with the inclusion of solvent molecules. The systems are formed by a hydrogen-bonding network and host–guest type interactions between the building blocks. It was found that the native cyclodextrin and polyethylenimine are able to form stable systems when the reaction medium constitutes a polar solvent forming host–guest type complexes with cyclodextrin. A special consideration was paid on the detailed spectroscopic analyses of the obtained water-soluble constructs, including ROESY and diffusion-ordered (DOSY) NMR spectroscopy studies. The versatility and significance of DOSY technique for the analysis of the cyclodextrin complexes and its non-covalent systems with branched polymers, were presented. It was also found that the guest molecules that were incorporated in the complexes exhibited enhanced thermal stability. The morphological details in the solid state were obtained by scanning electron microscope.Graphical

Failure of Density Functional Dispersion Correction in Metallic Systems and Its Possible Solution Using a Modified Many-Body Dispersion Correction.

Previous density functional dispersion corrections to density functional theory lead to an unphysical description of metallic systems, as exemplified by alkali and alkaline earth compounds. We demonstrate that it is possible to remedy this limitation by including screening effects into the form of interacting smeared-out dipoles in the many-body expansion of the interaction. Our new approach, called the coupled fluctuating smeared dipole model, describes equally well noncovalent systems, such as molecular pairs and crystals, and metallic systems.

Recent advances in mechanoluminescent polymers

In recent years, mechanoluminescence from polymers is emerging as a new cutting-edge area of polymer mechanochemistry research. It refers to the release of energy from polymers in the form of light when they are under various mechanical stimuli. To spur more researchers to join in such interesting and new burgeoning area, and promote its development to practical applications, in this review, we try to briefly summarize the recent advances in mechanoluminescent polymers with the aspects of non-covalent, covalent, and cascade reactions systems. We pay much attention on the applications of such polymer systems in molecular level failure and stress sensors, and give a perspective of their potential applications in novel energy conversion materials and devices, as well as self-healing materials.