Hydrogen bonds (HB)s are the most abundant motifs in biological systems. They play a key role in determining protein-ligand binding affinity and selectivity. We designed two pharmaceutically ...beneficial HB databases, database A including ca. 12,000 protein-ligand complexes with ca. 22,000 HBs and their geometries, and database B including ca. 400 protein-ligand complexes with ca. 2200 HBs, their geometries, and bond strengths determined via our local vibrational mode analysis. We identified seven major HB patterns, which can be utilized as a de novo QSAR model to predict the binding affinity for a specific protein-ligand complex. Glycine was reported as the most abundant amino acid residue in both donor and acceptor profiles, and N-H⋯O was the most frequent HB type found in database A. HBs were preferred to be in the linear range, and linear HBs were identified as the strongest. HBs with HB angles in the range of 100-110°, typically forming intramolecular five-membered ring structures, showed good hydrophobic properties and membrane permeability. Utilizing database B, we found a generalized Badger's relationship for more than 2200 protein-ligand HBs. In addition, the strength and occurrence maps between each amino acid residue and ligand functional groups open an attractive possibility for a novel drug-design approach and for determining drug selectivity and affinity, and they can also serve as an important tool for the hit-to-lead process.
LModeAGen, a new protocol for the automatic determination of a nonredundant, complete set of local vibrational modes is reported, which is based on chemical graph concepts. Whereas local mode ...properties can be calculated for a selection of parameters targeting specific local modes of interest, a complete set of nonredundant local mode parameters is requested for the adiabatic connection scheme (ACS), relating each local vibrational mode with a normal mode counterpart, and for the decomposition of normal modes (CNM) in terms of local mode contributions, a unique way to analyze vibrational spectra. So far, nonredundant parameter sets have been generated manually following chemical intuition or from a set of redundant parameters in a trial-and-error fashion, which has hampered the study of larger systems with hundreds of parameters. LModeAGen was successfully applied for a test set of 11 systems, ranging from small molecules to the large QM (>100 atoms) subsystem of carbomonoxy-neuroglobin protein, described with a hybrid QM/MM method. The ωB97X-D/aug-cc-pVDZ, M06L/def2-TZVP, and QM/MM ωB97X-D/6-31G(d,p)/AMBER model chemistries were adopted for the description of the molecules in the test set. Our new protocol is an important step forward for a routine ACS and CNM analysis of the vibrational spectra of complex and large systems with hundreds of atoms, providing new access to important encoded electronic structure information.
The Local Vibrational Mode Analysis, initially applied to diverse molecular systems, was extended to periodic systems in 2019. This work introduces an enhanced version of the LModeA software, ...specifically designed for the comprehensive analysis of two and three‐dimensional periodic structures. Notably, a novel interface with the Crystal package was established, enabling a seamless transition from molecules to periodic systems using a unified methodology. Two distinct sets of uranium‐based systems were investigated: (i) the evolution of the Uranyl ion (UO 22+) traced from its molecular configurations to the solid state, exemplified by Cs 2UO 2Cl 4 and (ii) Uranium tetrachloride (UCl 4) in both its molecular and crystalline forms. The primary focus was on exploring the impact of crystal packing on key properties, including IR and Raman spectra, structural parameters, and an in‐depth assessment of bond strength utilizing local mode perspectives. This work not only demonstrates the adaptability and versatility of LModeA for periodic systems but also highlights its potential for gaining insights into complex materials and aiding in the design of new materials through fine‐tuning.
In the past months, the use of the drug hydroxychloroquine has considerably increased in many countries, associated with a proposed treatment for the COVID-19 disease. Although there is no conclusive ...evidence about the efficacy of the drug for this purpose, surprisingly there are no conclusive studies in the literature concerning its mechanism of action inside cells, which is related to its interaction with nucleic acids. Here, we performed a robust characterization of the interaction between hydroxychloroquine and double-stranded DNA using single-molecule force spectroscopy and gel electrophoresis. Two different binding modes were identified, namely, minor groove binding for low drug concentrations and intercalation for high drug concentrations, and the sets of binding parameters were determined for each of these modes. Such results have unraveled in detail the molecular mechanism of action of the drug as a DNA ligand.
By employing time‐dependent density functional theory for solid‐state chemistry, the research presented by Andrii Shyichuk Acta Cryst. (2023), B67, 437–449 significantly contributes to the ...understanding of electron/hole traps in doped materials.
By employing time‐dependent density functional theory for solid‐state chemistry, the research presented by Andrii Shyichuk Acta Cryst. (2023), B67, 437–449 significantly contributes to the understanding of electron/hole traps in doped materials.
Uranium metallocenes have recently attracted attention driven by their use as catalysts in organometallic synthesis. In addition to bent U(IV) and U(III), an U(II) metallocene (η5-C5 i Pr5)2U was ...synthesized with an unusual linear Cp–U–Cp angle. In this work, we investigated 22 U(II) metallocenes, (i) assessing the intrinsic strength of the U-ring interactions in these complexes with a novel bond strength measure based on our local vibrational mode analysis and (ii) systematically exploring what makes these U(II) metallocenes bent. We included relativistic effects through the NESCau Hamiltonian and complemented the local mode analysis with natural bonding orbital (NBO) and quantum theory of atoms in molecules (QTAIM) data. Our study led to the following results: (i) reduction of bulky U-ring ligand substituents does not lead to bent complexes for alkyl substituents ( i Pr and i Bu) in contrast to SiMe3 ring substituents, which are all bent. (ii) The most bent complexes are (η5-C5H4SiMe3)2U (130°) and η5-P5H5)2U (143°). (iii) Linear complexes showed one hybridized NBO with s/d character, while bent structures were characterized by s/d/f mixing. (iv) We did not observe a correlation between the strength of the U-ring interaction and the amount of the ring-U-ring bend; the strongest interaction was found for η5-Cp)2U and the weakest for η5-P5H5)2U. In conclusion, our results provide a foundation for the design of U(II) metallocenes with specific physicochemical properties and increased reactivity.
•A novel questionnaire instrument for the quantitative behavioral assessment of pet cats by their owners was developed.•A convenience sample of 2068 cat owners completed an initial online survey ...regarding their cats’ behavior.•Twenty-three behavioral factors/subscales were extracted by exploratory factor analysis.•Seventeen of these 23 factors displayed adequate-high internal reliability.•The majority of factors/items also demonstrated adequate construct validity.
A questionnaire instrument for obtaining quantitative behavioral evaluations of pet cats from cat owners was developed and validated. Exploratory Factor Analysis of 2608 questionnaire responses to 149 behavioral questions/items extracted a total of 23 distinct factors that measured most of the more common dimensions of cat behavior. Seventeen of the 23 factors demonstrated adequate–high internal reliability (Cronbach’s alpha=0.712–0.923). Questionnaire validation was accomplished by determining: (a) whether owners’ subjective ratings of the severity of their cat’s behavior problems were associated with cats’ actual scores on expected questionnaire factors, (b) whether expected associations between specific demographic and/or lifestyle characteristics and behavior were confirmed by cats’ factor or item scores on the questionnaire, and (c) whether breed rankings based on owner-reported factor scores matched those previously derived from the opinions of experts (veterinarians). The results of these various tests confirmed the overall construct validity of the questionnaire.
Five novel Eu(III)-β-diketonate complexes containing ruthenocene ancillary ligands (1,1′-bis(diphenylphosphoryl)ruthenoceneRcBPO) were synthesized and characterized. The coordination compounds ...presented the general formula Eu(β-dik)3(RcBPO), where β-dik stands for 2-thenoyltrifluoroacetonate (tta), 3-benzoyl-1,1,1-trifluoroacetone (btf), 2-dibenzoylmethanate (dbm), 2-acetyl-1,3-indandionate (aind), and 2-benzoyl-1,3-indandionate (bind), and RcBPO stands for 1,1′-bis(diphenylphosphoryl)ruthenocene. The Eu(aind)3(RcBPO) complex crystallizes in a monoclinic Cc non-centrosymmetric space group with the europium site environment, assuming a bicapped trigonal prism coordination polyhedron with the symmetry point group close to C 2v . Photoluminescent properties for the solid-state samples were described in terms of excitation, emission, lifetime decay curves, and intrinsic and overall quantum yields. The replacement of the two coordinated H2O molecules by the RcBPO ancillary ligand leads to great enhancements of the overall quantum yields (Q Eu L), with the minimum increment by a factor of 5 for the case of Eu(btf)3(RcBPO) and the maximum enhancement of 270 times for the case of the Eu(dbm)3(RcBPO) complex. In addition, theoretical calculations were carried out to model the spectroscopic properties of the investigated compounds. To obtain theoretical Judd–Ofelt parameters (Ωλ, λ = 2, 4, and 6) and intramolecular energy transfer rates, the JOYSpectra web platform was employed using the structure obtained from density functional theory calculations. Hence, a rate equation model provided theoretical overall quantum yields, which are in great agreement with measured data.
The characterization of normal mode (CNM) procedure coupled with an adiabatic connection scheme (ACS) between local and normal vibrational modes, both being a part of the Local Vibrational Mode ...theory developed in our group, can identify spectral changes as structural fingerprints that monitor symmetry alterations, such as those caused by Jahn-Teller (JT) distortions. Employing the PBE0/Def2-TZVP level of theory, we investigated in this proof-of-concept study the hexaaquachromium cation case,
Cr
(
OH
2
)
6
3
+
/
Cr
(
OH
2
)
6
2
+
, as a commonly known example for a JT distortion, followed by the more difficult ferrous and ferric hexacyanide anion case,
Fe
(
CN
)
6
4
-
/
Fe
(
CN
)
6
3
-
. We found that in both cases CNM of the characteristic normal vibrational modes reflects delocalization consistent with high symmetry and ACS confirms symmetry breaking, as evidenced by the separation of axial and equatorial group frequencies. As underlined by the Cremer-Kraka criterion for covalent bonding, from
Cr
(
OH
2
)
6
3
+
to
Cr
(
OH
2
)
6
2
+
there is an increase in axial covalency whereas the equatorial bonds shift toward electrostatic character. From
Fe
(
CN
)
6
4
-
to
Fe
(
CN
)
6
3
-
we observed an increase in covalency without altering the bond nature. Distinct
π
back-donation disparity could be confirmed by comparison with the isolated
CN
-
system. In summary, our study positions the CNM/ACS protocol as a robust tool for investigating less-explored JT distortions, paving the way for future applications.
Graphical abstract
The adiabatic connection scheme relates local to normal modes, with symmetry breaking giving rise to axial and equatorial group local frequencies
Microfluidic-based platforms have become a hallmark for chemical and biological assays, empowering micro- and nano-reaction vessels. The fusion of microfluidic technologies (digital microfluidics, ...continuous-flow microfluidics, and droplet microfluidics, just to name a few) presents great potential for overcoming the inherent limitations of each approach, while also elevating their respective strengths. This work exploits the combination of digital microfluidics (DMF) and droplet microfluidics (DrMF) on a single substrate, where DMF enables droplet mixing and further acts as a controlled liquid supplier for a high-throughput nano-liter droplet generator. Droplet generation is performed at a flow-focusing region, operating on dual pressure: negative pressure applied to the aqueous phase and positive pressure applied to the oil phase. We evaluate the droplets produced with our hybrid DMF-DrMF devices in terms of droplet volume, speed, and production frequency and further compare them with standalone DrMF devices. Both types of devices enable customizable droplet production (various volumes and circulation speeds), yet hybrid DMF-DrMF devices yield more controlled droplet production while achieving throughputs that are similar to standalone DrMF devices. These hybrid devices enable the production of up to four droplets per second, which reach a maximum circulation speed close to 1540 µm/s and volumes as low as 0.5 nL.
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