Academic literature on the topic 'Exited state molecular dunamics'

Organic molecules with excited-state intramolecular proton transfer (ESIPT) and thermally activated delayed fluorescence (TADF) properties have great potential for realizing efficient organic light-emitting diodes (OLEDs). Furthermore, 2,2′-bipyridine-3,3′-diol (BP(OH)2) is a typical molecule with ESIPT and TADF properties. Previously, the double ESIPT state was proved to be a luminescent state, and the T2 state plays a dominant role in TADF for the molecule. Nevertheless, whether BP(OH)2 undergoes a double or single ESIPT process is controversial. Since different ESIPT channels will bring different TADF mechanisms, the previously proposed TADF mechanism based on the double ESIPT structure for BP(OH)2 needs to be reconsidered. Herein, reduced density gradient, potential energy surface, IR spectra and exited-state hydrogen-bond dynamics computations confirm that BP(OH)2 undergoes the barrierless single ESIPT process rather than the double ESIPT process with a barrier. Moreover, based on the single ESIPT structure, we calculated spin-orbit coupling matrix elements, nonradiative rates and electron-hole distributions. These results disclose that the T3 state plays a predominant role in TADF. Our investigation provides a better understanding on the TADF mechanism in hydrogen-bonded molecular systems and the interaction between ESIPT and TADF, which further provides a reference for developing efficient OLEDs.

ABSTRACT Positive transcription elongation factor b (P-TEFb) is the major metazoan RNA polymerase II (Pol II) carboxyl-terminal domain (CTD) Ser2 kinase, and its activity is believed to promote productive elongation and coupled RNA processing. Here, we demonstrate that P-TEFb is critical for the transition of Pol II into a mature transcription elongation complex in vivo. Within 3 min following P-TEFb inhibition, most polymerases were restricted to within 150 bp of the transcription initiation site of the active Drosophila melanogaster Hsp70 gene, and live-cell imaging demonstrated that these polymerases were stably associated. Polymerases already productively elongating at the time of P-TEFb inhibition, however, proceeded with elongation in the absence of active P-TEFb and cleared from the Hsp70 gene. Strikingly, all transcription factors tested (P-TEFb, Spt5, Spt6, and TFIIS) and RNA-processing factor CstF50 exited the body of the gene with kinetics indistinguishable from that of Pol II. An analysis of the phosphorylation state of Pol II upon the inhibition of P-TEFb also revealed no detectable CTD Ser2 phosphatase activity upstream of the Hsp70 polyadenylation site. In the continued presence of P-TEFb inhibitor, Pol II levels across the gene eventually recovered.

ABSTRACT CDK9 is a CDC2-related kinase and the catalytic subunit of the positive-transcription elongation factor b and the Tat-activating kinase. It has recently been reported that CDK9 is a short-lived protein whose levels are regulated during the cell cycle by the SCFSKP2 ubiquitin ligase complex (R. E. Kiernan et al., Mol. Cell. Biol. 21:7956-7970, 2001). The results presented here are in contrast to those observations. CDK9 protein levels remained unchanged in human cells entering and progressing through the cell cycle from G0, despite dramatic changes in SKP2 expression. CDK9 levels also remained unchanged in cells exiting from mitosis and progressing through the next cell cycle. Similarly, the levels of CDK9 protein did not change as cells exited the cell cycle and differentiated along various lineages. In keeping with these observations, the kinase activity associated with CDK9 was found to not be regulated during the cell cycle. We have also found that endogenous CDK9 is a very stable protein with a half-life (t 1/2) of 4 to 7 h, depending on the cell type. In contrast, when CDK9 is overexpressed, it is not stabilized and is rapidly degraded, with a t 1/2 of less than 1 h, depending on the level of expression. Treatment of cells with proteasome inhibitors blocked the degradation of short-lived proteins, such as p27, but did not affect the expression of endogenous CDK9. Ectopic overexpression of SKP2 led to reduction of p27 protein levels but had no effect on the expression of endogenous CDK9. Finally, downregulation of endogenous SKP2 gene expression by interfering RNA had no effect on CDK9 protein levels, whereas p27 protein levels increased dramatically. Therefore, the SCFSKP2 ubiquitin ligase does not regulate CDK9 expression in a cell cycle-dependent manner.

There are basically two ways to determine precision values for nuclear quadrupole moments (Q): measurements for stable or reasonably long-lived (mostly ground) states by atomic and molecular spectroscopy and measurements for much shorter-lived excited states using nuclear condensed-matter techniques like Mössbauer or perturbed-angular distribution and correlation (PAC) spectroscopy. In all cases, the direct experimental result is the product of the electric-field gradient (EFG) at the nuclear site with Q. The EFG for atomic and simple molecular systems can now mostly be calculated by theory with good accuracy, while the present status of density functional calculations of solid-state systems used for short-lived excited states limits the accuracy, generally to a 10%–20% level. Thus, the EFG of at least one matrix where data for exited states exist must be calibrated by measuring a ground state with known Q using magnetic or quadrupole resonance. This procedure is obviously not applicable to elements having no stable isotope with I > 1/2. For Cd, the problem has now been overcome using a concept proposed in Berkeley half a century ago, measuring isolated free Cd (and Hg) molecules with PAC. A similar project for Pb ongoing at ISOLDE/CERN is sketched, as well as a related one for Sn.

Recent experiments have shown that mRNAs can move between polysomes and P-bodies, which are aggregates of nontranslating mRNAs associated with translational repressors and the mRNA decapping machinery. The transitions between polysomes and P-bodies and how the poly(A) tail and the associated poly(A) binding protein 1 (Pab1p) may affect this process are unknown. Herein, we provide evidence that poly(A)+mRNAs can enter P-bodies in yeast. First, we show that both poly(A)−and poly(A)+mRNA become translationally repressed during glucose deprivation, where mRNAs accumulate in P-bodies. In addition, both poly(A)+transcripts and/or Pab1p can be detected in P-bodies during glucose deprivation and in stationary phase. Cells lacking Pab1p have enlarged P-bodies, suggesting that Pab1p plays a direct or indirect role in shifting the equilibrium of mRNAs away from P-bodies and into translation, perhaps by aiding in the assembly of a type of mRNP within P-bodies that is poised to reenter translation. Consistent with this latter possibility, we observed the translation initiation factors (eIF)4E and eIF4G in P-bodies at a low level during glucose deprivation and at high levels in stationary phase. Moreover, Pab1p exited P-bodies much faster than Dcp2p when stationary phase cells were given fresh nutrients. Together, these results suggest that polyadenylated mRNAs can enter P-bodies, and an mRNP complex including poly(A)+mRNA, Pab1p, eIF4E, and eIF4G2 may represent a transition state during the process of mRNAs exchanging between P-bodies and translation.

Abstract Inhalation of environmental particles and herpesvirus infection are ubiquitous in our society. Herpesviruses persist lifelong in the host in a latent state, which can be exited by stress-induced reactivation with production of lytic virus. Our previous investigations show that pulmonary exposure to carbon nanoparticles (CNP) triggers reactivation of latent murine gammaherpesvirus 68 (MHV-68) in mouse lungs, mainly localizing to CD11b+ infiltrating macrophages and dependent on p38 MAPK signaling. Furthermore, we observed that a two-time repeated CNP administration to latently infected mice resulted in alveolar damage leading to progressive emphysema. However, the underlying adverse mechanisms causing alveolar damage and the corresponding cell communication upon CNP exposure in latently infected lungs is still unclear. To investigate this, we developed a 3D lung organoid culture from primary murine epithelial cells in combination with persistently MHV-68 infected macrophages. This model enables us to detect reactivation and cytokine release upon CNP exposure, and to gain insights into the cellular communication of epithelial cells and macrophages, to understand the mechanisms underlying reactivation-triggered damage. In parallel, adverse effects of this second hit scenario on the alveolar epithelium and subsequent disease development get investigated in vivo. Latently infected mice are exposed to CNP up to 5 times, and virus reactivation and further epithelial damage is analyzed. By uncovering molecular mechanisms underlying the adverse effects and elucidating the communication occurring in vitro and in vivo we want to identify potential targets to prevent exacerbation of lung diseases caused by these two omnipresent factors, herpesvirus infection and ambient particle exposure.

AbstractHSP90 are abundant molecular chaperones, assisting the folding of several hundred client proteins, including substrates involved in tumor growth or neurodegenerative diseases. A complex set of large ATP-driven structural changes occurs during HSP90 functional cycle. However, the existence of such structural rearrangements in apo HSP90 has remained unclear. Here, we identify a metastable excited state in the isolated human HSP90α ATP binding domain. We use solution NMR and mutagenesis to characterize structures of both ground and excited states. We demonstrate that in solution the HSP90α ATP binding domain transiently samples a functionally relevant ATP-lid closed state, distant by more than 30 Å from the ground state. NMR relaxation enables to derive information on the kinetics and thermodynamics of this interconversion, while molecular dynamics simulations establish that the ATP-lid in closed conformation is a metastable exited state. The precise description of the dynamics and structures sampled by human HSP90α ATP binding domain provides information for the future design of new therapeutic ligands.

Diapause arrest in animals such as Caenorhabditis elegans is tightly regulated so that animals make appropriate developmental decisions amidst environmental challenges. Fully understanding diapause requires mechanistic insight of both entry and exit from the arrested state. While a steroid hormone pathway regulates the entry decision into Caenorhabditis elegans dauer diapause, its role in the exit decision is less clear. A complication to understanding steroid hormonal regulation of dauer has been the peculiar fact that steroid hormone mutants such as daf-9 form partial dauers under normal growth conditions. Here, we corroborate previous findings that daf-9 mutants remain capable of forming full dauers under unfavorable growth conditions and establish that the daf-9 partial dauer state is likely a partially exited dauer that has initiated but cannot complete the dauer exit process. We show that the steroid hormone pathway is both necessary for and promotes complete dauer exit, and that the spatiotemporal dynamics of steroid hormone regulation during dauer exit resembles that of dauer entry. Overall, dauer entry and dauer exit are distinct developmental decisions that are both controlled by steroid hormone signaling.

Abstract The excited-state dynamics of molecular materials is of great importance to understand early time photodynamics. We have used Femtosecond Transient Absorption (fs-TA) and Ultrafast Raman Loss Spectroscopy (URLS) spectroscopy to understand early time photophysical dynamics in the ultrafast timescale. fs-TA measures the electronic absorption of photoexcited molecule revealing the population dynamics on the complex potential manifold. Whereas, URLS measures the vibrational signature of excited species that depicting the structural dynamics during the evolution. Such ultrafast spectroscopic methods are very essential to unravel the early time events of photophysical and photochemical processes. We performed time-resolved URLS measurements (stimulated Raman scattering based on third-order nonlinear spectroscopic principles) by choosing the actinic pump in the UV-Vis region, Raman pump in the visible region and Raman probe as a broadband white light continuum to understand intricacies related to the excited state dynamics in few interesting systems Singlet Fission (SF), a spin allowed fast internal conversion process of multiexciton generation from photoexcited singlet 〖(S〗_0) exciton in which a pair of correlated triplet exciton 〖(TT)〗^1 is formed. SF can overcome Shockley-queisser limit and vastly improve photo-energy conversion efficiency. We have studied the SF process in the solution phase for 9,10-Bis(phenylethynyl) anthracene (BPEA) to understand the electronic and structural dynamics in ultrafast time-scale. The extent of electronic coupling between singlet exciton and triplet pair state governs the efficiency of SF process. SF is very efficient for crystalline forms, as a consequence tracking the initial events related to evolution from the initial singlet state to two triplet states is non-trivial due to ultrafast in nature. However, in solution, SF is essentially limited by the diffusion. Here, the dynamics of the BPEA (in solution) in the entangled singlet and multi-excitonic states is elucidated in terms of the intricate structural dynamics, which is otherwise non-trivial from fs-TA measurements alone. The study of the effect of coupled electronic states for the SF process in BPEA has been studied next. In BPEA, a strong one-photon allowed electronic transition (B_1u) with long axis polarization is overlapped with moderately allowed short-axis polarized electronic transition (B_2u). These two electronic states are coupled via Pseudo Jahn-Teller coupling along with modes having b_3g symmetry. The TA of the excited species is a result of overlapping spectral signatures from both hot-multiexcitionic and moderately allowed states. The photoexcitation of BPEA in n-hexane (HX) at different wavelengths across the steady-state absorption spectrum exhibits a distinct intensity ratio of these two transient absorption bands although their normalized intensity kinetics show similar behaviour. However, with URLS, it is shown that the modes that are involved in the Pseudo-Jahn-Teller coupling exhibit distinct response as a consequence of quantum interference of the Raman polarizabilities related to such states. We have performed an extensive quantum mechanical calculation by utilizing Gaussian 09 software to understand the experimentally observed absorption, vibrational spectra by means of orbital calculation, orbital symmetry, oscillator strength calculation, vibrational frequency calculation, energy level diagram along specific coordinates. The corroboration of quantum calculation with experimentally observed data provides a deeper understanding of the photodynamics particularly in the excited state analysis. Next, we have investigated the excess energy dissipation and isomerization process in excited t-stilbene in the condensed phase. Upon photoexcitation, the excess energy is deposited in the initially prepared Franck-Condon (FC) excited state. However, such energy is redistributed among intramolecular modes and subsequently dissipated to the solvent molecules through anharmonic coupling and solute-solvent coupling respectively. The energy dissipation process can be described by two exchange parameters i.e., backward exchange rate (W_1) and forward exchange rate (W_2) that are related to the thermally generated exciton in the bath and the low-frequency solute modes respectively. Here, the influence of alkane chain length of solvents on the exchange rates and associated mode coupling is elucidated in terms of the W_2/W_1 ratio. Finally, a detailed analytical calculation has been performed to compute the third- order nonlinear susceptibility that contributes to the URLS signatures. It also depicts the method of identifying the relevant quantum processes using closed path time loop (CPTL) Feynman diagrams. Here, it is clearly demonstrated the underlying reasons for asymmetry in the intensity between gain (Stokes) and loss (anti-Stokes) signatures of URLS process. A model simulation has been carried out with different molecular parameters.