| 1. |
- Durbeej, Bo, 1973-, et al.
(författare)
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Molecular Photoswitching Aided by Excited-State Aromaticity
- 2018
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Ingår i: ChemPlusChem. - Weinheim, Germany : Wiley-VCH Verlagsgesellschaft. - 2192-6506. ; 83:11, s. 958-967
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Tidskriftsartikel (refereegranskat)abstract
- Central to the development of optoelectronic devices is the availability of efficient synthetic molecular photoswitches, the design of which is an arena where the evolving concept of excited‐state aromaticity (ESA) is yet to make a big impact. The aim of this minireview is to illustrate the potential of this concept to become a key tool for the future design of photoswitches. The paper starts with a discussion of challenges facing the use of photoswitches for applications and continues with an account of how the ESA concept has progressed since its inception. Then, following some brief remarks on computational modeling of photoswitches and ESA, the paper describes two different approaches to improve the quantum yields and response times of switches driven by E/Z photoisomerization or photoinduced H‐atom/proton transfer reactions through simple ESA considerations. It is our hope that these approaches, verified by quantum chemical calculations and molecular dynamics simulations, will help stimulate the application of the ESA concept as a general tool for designing more efficient photoswitches and other functional molecules used in optoelectronic devices.
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| 2. |
- Fang, Changfeng, et al.
(författare)
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Computational study of the working mechanism and rate acceleration of overcrowded alkene-based light-driven rotary molecular motors
- 2014
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 4:20, s. 10240-10251
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, much progress has been made in the design, synthesis and operation of light-driven rotary molecular motors based on chiral overcrowded alkenes. Through consecutive cis–trans photoisomerization and thermal helix inversion steps, where the latter dictate the overall rate of rotation, these motors achieve a full 360° unidirectional rotation around the carbon–carbon double bond connecting the two (rotator and stator) alkene halves. In this work, we report quantum chemical calculations indicating that a particularly fast-rotating overcrowded alkene-based motor capable of reaching the MHz regime, can be made to rotate even faster by the substitution of a rotator methyl group with a methoxy group. Specifically, using density functional theory methods that reproduce the rate-limiting 35 kJ mol−1 thermal free-energy barriers shown by the methyl-bearing motor with errors of 5 kJ mol−1 only, it is predicted that this substitution reduces these barriers by a significant 15–20 kJ mol−1. This prediction is preceded by a series of benchmark calculations for assessing how well density functional theory methods account for available experimental data (crystallographic, UV-vis absorption, thermodynamic) on the rotary cycles of overcrowded alkenes, and a detailed examination of the thermal and photochemical reaction mechanisms of the original motor of this type.
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| 3. |
- Fang, Changfeng, et al.
(författare)
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How method-dependent are calculated differences between vertical, adiabatic, and 0-0 excitation energies?
- 2014
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 118:23, s. 4157-4171
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Tidskriftsartikel (refereegranskat)abstract
- Through a large number of benchmark studies, the performance of different quantum chemical methods in calculating vertical excitation energies is today quite well established. Furthermore, these efforts have in recent years been complemented by a few benchmarks focusing instead on adiabatic excitation energies. However, it is much less well established how calculated differences between vertical, adiabatic and 0-0 excitation energies vary between methods, which may be due to the cost of evaluating zero-point vibrational energy corrections for excited states. To fill this gap, we have calculated vertical, adiabatic, and 0-0 excitation energies for a benchmark set of molecules covering both organic and inorganic systems. Considering in total 96 excited states and using both TD-DFT with a variety of exchange-correlation functionals and the ab initio CIS and CC2 methods, it is found that while the vertical excitation energies obtained with the various methods show an average (over the 96 states) standard deviation of 0.39 eV, the corresponding standard deviations for the differences between vertical, adiabatic, and 0-0 excitation energies are much smaller: 0.10 (difference between adiabatic and vertical) and 0.02 eV (difference between 0-0 and adiabatic). These results provide a quantitative measure showing that the calculation of such quantities in photochemical modeling is well amenable to low-level methods. In addition, we also report on how these energy differences vary between chemical systems and assess the performance of TD-DFT, CIS, and CC2 in reproducing experimental 0-0 excitation energies.
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| 4. |
- Kalapos, Peter Pal, et al.
(författare)
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Photoswitching of Local (Anti)Aromaticity in Biphenylene-Based Diarylethene Molecular Switches
- 2022
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 87:15, s. 9532-9542
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Tidskriftsartikel (refereegranskat)abstract
- Photoinduced tuning of (anti)aromaticity and associated molecular properties is currently in the focus of attention for both tailoring photochemical reactivity and designing new materials. Here, we report on the synthesis and spectroscopic characterization of diarylethene-based molecular switches embedded in a biphenylene structure composed of rings with different levels of local (anti)aromaticity. We show that it is possible to modulate and control the (anti)aromatic character of each ring through reversible photoswitching of the aryl units of the system between open and closed forms. Remarkably, it is shown that the irreversible formation of an annulated bis(dihydro-thiopyran) side-product that hampers the photoswitching can be efficiently suppressed when the aryl core formed by thienyl groups in one switch is replaced by thiazolyl groups in another.
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| 5. |
- Oruganti, Baswanth, et al.
(författare)
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Activation of Abl1 Kinase Explored Using Well-Tempered Metadynamics Simulations on an Essential Dynamics Sampled Path
- 2021
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 17:11, s. 7260-7270
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Tidskriftsartikel (refereegranskat)abstract
- Well-tempered metadynamics (wT-metaD) simulations using path collective variables (CVs) have been successfully applied in recent years to explore conformational transitions in protein kinases and other biomolecular systems. While this methodology has the advantage of describing the transitions with a limited number of predefined path CVs, it requires as an input a reference path connecting the initial and target states of the system. It is desirable to automate the path generation using approaches that do not rely on the choice of geometric CVs to describe the transition of interest. To this end, we developed an approach that couples essential dynamics sampling with wT-metaD simulations. We used this newly developed procedure to explore the activation mechanism of Abl1 kinase and compute the associated free energy barriers. Through these simulations, we identified a three-step mechanism for the activation that involved two metastable intermediates that possessed a partially open activation loop and differed primarily in the "in" or "out" conformation of the aspartate residue of the DFG motif. One of these states is similar to a conformation that was detected in previous spectroscopic studies of Abl1 kinase, albeit its mechanistic role in the activation was hitherto not well understood. The present study establishes its intermediary role in the activation and predicts a rate-determining free energy barrier of 13.8 kcal/mol that is in good agreement with previous experimental and computational estimates. Overall, our study demonstrates the usability of essential dynamics sampling as a path CV in wT-metaD to conveniently study conformational transitions and accurately calculate the associated barriers.
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| 6. |
- Oruganti, Baswanth, et al.
(författare)
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Allosteric enhancement of the BCR-Abl1 kinase inhibition activity of nilotinib by cobinding of asciminib
- 2022
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Ingår i: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 298:8
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors that bind competitively to the ATP binding pocket in the kinase domain of the oncogenic fusion protein BCR-Abl1 are used successfully in targeted therapy of chronic myeloid leukemia (CML). Such inhibitors provided the first proof of concept that kinase inhibition can succeed in a clinical setting. However, emergence of drug resistance and dose-dependent toxicities limit the effectiveness of these drugs. Therefore, treatment with a combination of drugs without overlapping resistance mechanisms appears to be an appropriate strategy. In the present work, we explore the effectiveness of combination therapies of the recently developed allosteric inhibitor asciminib with the ATP-competitive inhibitors nilotinib and dasatinib in inhibiting the BCR-Abl1 kinase activity in CML cell lines. Through these experiments, we demonstrate that asciminib significantly enhances the inhibition activity of nilotinib, but not of dasatinib. Exploring molecular mechanisms for such allosteric enhancement via systematic computational investigation incorporating molecular dynamics, metadynamics simulations, and density functional theory calculations, we found two distinct contributions. First, binding of asciminib triggers conformational changes in the inactive state of the protein, thereby making the activation process less favorable by similar to 4 kcal/mol. Second, the binding of asciminib decreases the binding free energies of nilotinib by similar to 3 and similar to 7 kcal/mol for the wildtype and T315I-mutated protein, respectively, suggesting the possibility of reducing nilotinib dosage and lowering risk of developing resistance in the treatment of CML.
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| 7. |
- Oruganti, Baswanth, et al.
(författare)
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Assessment of a composite CC2/DFT procedure for calculating 0-€“0 excitation energies of organic molecules
- 2016
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Ingår i: Molecular Physics. - : Taylor & Francis. - 0026-8976 .- 1362-3028. ; 114:23, s. 3448-3463
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Tidskriftsartikel (refereegranskat)abstract
- The task to assess the performance of quantum chemical methods in describing electronically excited states has in recent years started to shift from calculation of vertical (ΔEve) to calculation of 0-€“0 excitation energies (ΔE00). Here, based on a set of 66 excited states of organic molecules for which high-resolution experimental ΔE00 energies are available and for which the approximate coupled-cluster singles and doubles (CC2) method performs particularly well, we explore the possibility to simplify the calculation of CC2-quality ΔE00 energies using composite procedures that partly replace CC2 with more economical methods. Specifically, we consider procedures that employ CC2 only for the ΔEve part and density functional theory methods for the cumbersome excited-state geometry optimisations and frequency calculations required to obtain ΔE00 energies from ΔEve ones. The results demonstrate that it is indeed possible to both closely (to within 0.06-€“0.08 eV) and consistently approximate ‘true’ CC2 ΔE00 energies in this way, especially when CC2 is combined with hybrid density functionals. Overall, the study highlights the unexploited potential of composite procedures, which hitherto have found widespread use mostly in ground-state chemistry, to also play an important role in facilitating accurate studies of excited states.
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| 8. |
- Oruganti, Baswanth, et al.
(författare)
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Computational design of faster rotating second-generation light-driven molecular motors by control of steric effects
- 2015
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 17:33, s. 21740-21751
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Tidskriftsartikel (refereegranskat)abstract
- We report a systematic computational investigation of the possibility to accelerate the rate-limiting thermal isomerizations of the rotary cycles of synthetic light-driven overcrowded alkene-based molecular motors through modulation of steric interactions. Choosing as a reference system a second-generation motor known to accomplish rotary motion in the MHz regime and using density functional theory methods, we propose a three-step mechanism for the thermal isomerizations of this motor and show that variation of the steric bulkiness of the substituent at the stereocenter can reduce the (already small) free-energy barrier of the rate-determining step by a further 15-17 kJ mol(-1). This finding holds promise for future motors of this kind to reach beyond the MHz regime. Furthermore, we demonstrate and explain why one particular step is kinetically favored by decreasing and another step is kinetically favored by increasing the steric bulkiness of this substituent, and identify a possible back reaction capable of impeding the rotary rate.
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| 9. |
- Oruganti, Baswanth, 1987-
(författare)
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Computational Design of Molecular Motors and Excited-State Studies of Organic Chromophores
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents computational quantum chemical studies of molecular motors and excited electronic states of organic chromophores.The first and major part of the thesis is concerned with the design of light-driven rotary molecular motors. These are molecules that absorb light energy and convert it into 360° unidirectional rotary motion around a double bond connecting two molecular halves. In order to facilitate potential applications of molecular motors in nanotechnology, such as in molecular transport or in development of materials with photo-controllable properties, it is critical to optimize the rates and efficiencies of the chemical reactions that produce the rotary motion. To this end, computational methods are in this thesis used to study two different classes of molecular motors.The first class encompasses the sterically overcrowded alkenes developed by Ben Feringa, co-recipient of the 2016 Nobel Prize in Chemistry. The rotary cycles of these motors involve two photoisomerization and two thermal isomerization steps, where the latter are the ones that limit the attainable rotational frequencies. In the thesis, several new motors of this type are proposed by identifying steric, electronic and conformational approaches to accelerate the thermal isomerizations. The second class contains motors that incorporate a protonated Schiff base and are capable to achieve higher photoisomerization rates than overcrowded alkene-based motors. In the thesis, a new motor of this type is proposed that produces unidirectional rotary motion by means of two photochemical steps alone. Also, this motor lacks both a stereocenter and helical motifs, which are key features of almost all synthetic rotary motors developed to date.The second part of the thesis focuses on the design and assessment of composite computational procedures for modeling excited electronic states of organic chromophores. In particular, emphasis is put on developing procedures that facilitate the calculations of accurate 0−0 excitation energies of such compounds in a cost-effective way by combining quantum chemical methods with different accuracies.
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| 10. |
- Oruganti, Baswanth, et al.
(författare)
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Computational Insight to Improve the Thermal Isomerisation Performance of Overcrowded Alkene-Based Molecular Motors through Structural Redesign
- 2016
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Ingår i: ChemPhysChem. - : Wiley-Blackwell Publishing Inc.. - 1439-4235 .- 1439-7641. ; 17:21, s. 3399-3408
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic overcrowded alkene-based molecular motors achieve 360° unidirectional rotary motion of one motor half (rotator) relative to the other (stator) through sequential photochemical and thermal isomerisation steps. In order to facilitate and expand the use of these motors for various applications, it is important to investigate ways to increase the rates and efficiencies of the reactions governing the rotary motion. Here, we use computational methods to explore whether the thermal isomerisation performance of some of the fastest available motors of this type can be further improved by reducing the sizes of the motor halves. Presenting three new redesigned motors that combine an indanylidene rotator with a cyclohexadiene, pyran or thiopyran stator, we first use multiconfigurational quantum chemical methods to verify that the photoisomerisations of these motors sustain unidirectional rotary motion. Then, by performing density functional calculations, we identify both stepwise and concerted mechanisms for the thermal isomerisations of the motors and show that the rate-determining free-energy barriers of these processes are up to 25 kJ mol−1 smaller than those of the original motors. Furthermore, the thermal isomerisations of the redesigned motors proceed in fewer steps. Altogether, the results suggest that the redesigned motors are useful templates for improving the thermal isomerisation performance of existing overcrowded alkene-based motors.
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