916 research outputs found
Traversing the Experimental and Computational Landscapes: Wielding, Refining, and Forging the Toolkit for Rational Design of Partially Fluorescent Near-Infrared BODIPY Photosensitizers for Image-Guided Photodynamic Therapy
No full textThe advances in healthcare of the past two centuries have drastically increased
our average life expectancy by mitigating the prevalence and lethality of
numerous conditions. In this progression, the challenge for maintaining our health
continuously shifts to conditions that are harder to cure. Herein cancer stands
undoubtedly as the final frontier, taking the lives of an estimated 10 million people
in 2020 and already having overtaken cardiovascular disorders as the leading cause
of death in several high-income countries. Although the survivability of cancer has
tremendously progressed through the reduction of risk factors, early diagnosis,
and improvements in well-established therapies such as surgery, radiotherapy,
and chemotherapy, the recent decades have been characterized by the rise of
alternative techniques like immunotherapy and photodynamic therapy.
The latter example is a light-based method that has been approved by the United
States Food and Drug Administration since 1995 and which is currently applied
in multiple countries for the treatment of a broad set of cancers. Photodynamic
therapy operates via a compound, commonly known as a photosensitizer, that
is capable of absorbing light and passing the therefrom obtained energy over to
oxygen molecules. The resulting excited, or singlet, oxygen is very reactive and
will immediately damage its close surroundings. This destructive effect can be
applied very specifically to cancer cells by letting the administered photosensitizer
preferentially accumulate inside tumor tissues and then activating it with a targeted
light irradiation, thereby leaving healthy tissue unharmed.
Despite carrying great potential, contemporary photodynamic therapy is held back
by the mediocre functioning of the currently available commercial photosensitizers.
Their composition can be ill-defined, they may have a poor distribution throughout
the body and clear very slowly from it, they use light that is easily scattered or
absorbed by biological tissues, and their lack of fluorescence does not allow their
location to be traced for diagnostic purposes. Thus, ideally, the photosensitizer
is a pure and partially fluorescent compound that possesses a powerful singlet
oxygen generation capacity and a strong absorption of red to near-infrared
light, as this penetrates the deepest into the tissue. This thesis constitutes one
of the many efforts that have been devoted towards the creation of better
photosensitizers, thereby taking a holistic approach by not only focusing on the
substances themselves, but also on the tools by which they are designed and
analyzed. The first part of the thesis is dedicated to those tools which make use of theoretical
quantum chemical models to calculate a broad scope of molecular properties that
are in many cases difficult to determine experimentally. Predicting these properties
is very useful for the preliminary screening of potential photosensitizers and for
revealing the intricate mechanisms governing their observed behavior. However,
the method by which this is done always provides an approximation of reality
and this is only of any value if it is sufficiently correct and if the amount of
computational resources required for it is reasonable. Density functional theory,
and its time-dependent form, is a technique with a comparatively great accuracy
for its cost, giving it its place as the de facto standard for experiment-adjacent
research. Yet, its performance is strongly dependent on the systems that are
being evaluated and the choice of its exchange-correlation functional. In order
to find an optimal procedure for investigating the class of compounds covered in
this thesis, an assessment of the consistency and accuracy of several parameters
and exchange-correlation functionals was carried out, thereby comparing to
experimental data of such compounds and to results obtained from a higher
level method, i.e., SCS-riCC2. In another chapter, a widely used measure for the
length of charge displacement during a molecular excitation was reconfigured to
a symmetry-independent form. That way, the charge transfer characteristics of
molecules and excitations can be analyzed regardless of their shape.
In the second part, these newly refined tools were utilized to successfully develop
partially fluorescent near-infrared-active photosensitizers. One employed approach
was to introduce photosensitization capacities to the strongly near-infrared
fluorescent pyrrolopyrrole aza-BODIPY dye. This was done by attaching an electron
rich structure to the electron poor dye, creating a donor-acceptor system capable
of forming charge transfer excited states that can serve as an intermediate for
the molecule to reach the state from which it generates singlet oxygen. The
same results can be achieved without a charge transfer state by twisting the
molecular geometry. The other approach, covered in the final chapter, was to
shift the absorption of a partially fluorescent twisted BODIPY photosensitizer to
the near-infrared, thereby also attempting to induce extra phototoxic power by
going for a donor-acceptor design. This second idea proved crucial for the success
of the project, as the red shift compromised the delicate twist-based mechanism.
Nevertheless, high-performing photosensitizers were obtained throughout the
thesis and with the computational insights gained during the effort, many new
promising photosensitizers are within reach
Investigating XC-functionals towards describing experimentally relevant excited-state properties of NIR-BODIPY derivatives
No full textThe predictive and analytical power of time-dependent density functional theory (TD-DFT) has been instrumental in the design and mechanistic understanding of numerous organic chromophores. Yet, the widely popular boron-dipyrromethene (BODIPY) dye class suffers from notorious TD-DFT accuracy issues, undermining the serviceability of the technique. Highly correlated wave function approaches are much better at reproducing photophysical properties but become computationally unviable when making the push towards larger near-infrared (NIR) active structures. In an effort to find the protocol most capable of helping experimentalists design and analyze novel NIR BODIPYs, we have benchmarked 11 global or range-separated hybrid exchange-correlation functionals (XCFs) with different amounts of Hartree-Fock exchange. By relating both transition energies and oscillator strengths, first through a set of resolution-of-the-identity second-order coupled cluster (riCC2) calculations and then directly to experimental data, it is revealed that M06-2X and M06-HF behave most consistently for singlet and triplet excitations. To optimize accuracy across states, we recommend a hybrid approach where singlets are obtained through full TD-DFT and triplets are treated using the Tamm-Dancoff approximation.</p
Earth Mover’s Charge Transfer Distance:A General and Robust Approach for Describing Excited State Locality
No full textA novel approach for assessing the extent of electron displacement in optical transitions is proposed by implementing the Earth Mover’s Distance (EMD) method, which quantifies the spatial dissimilarity between ground and excited state electron density distributions. In contrast to previous descriptors, this index provides a representative and intuitively understandable distance under a robust and computationally efficient scheme for all possible forms of locality, even in the most difficult to dissect topological cases. The theoretical differences among the existing indices and our method are first illustrated with the help of a simplified model system, followed by a benchmarking of several partial atomic charge models using experimentally relevant push-pull compounds with diverse symmetries. These same molecules are finally employed to further demonstrate the principal advantages of the EMD index and its capabilities in rationalizing charge transfer phenomena.</p
Mauersegler weiter Wege. Mathias Enard: Kompass
No full textAnalysis of the peculiar scientific narrative in the novel of the Prix-Goncourt winning author Mathias Enard
Les commissions électorales en Afrique de l'Ouest
No full text[author: Mathias Hounkpe ; Ismaila Madior Fall]Electronic ed.: Abuja ; Bonn : FES, 201
Paul Bourget, écrivain engagé
No full textPaul Bourget, A committed writer, Yehoshua Mathias.
In the France of the early twentieth century, Paul Bourget's figure is that of a successful novelist who became gradually a «committed author». A monarchist, deeply conservative, passionate defender of religion and the family as the vital bases of the social order, he thus became the bard of the bourgeois ethic faced with the destabilization of modernity.Mathias Yehoshua. Paul Bourget, écrivain engagé. In: Vingtième Siècle, revue d'histoire, n°45, janvier-mars 1995. pp. 14-29
„Nature must be felt“ – Alexander von Humboldt, pioneer of an ecological worldview and protagonist of „transversal reason“
No full textDer Text erinnert zum 250sten Geburtsjahr an Alexander von Humboldt, ein Vordenker für eine ökologische Sicht der Welt und ein früher Protagonist „transversaler Vernunft“. Er ist als Ideengeber für die „neuen Naturtherapien“, für die Integrative Therapie und für eine ökologische Sicht in der Psychotherapie eine unverzichtbare Quelle. Einige aus dieser Perspektive wichtige Aspekte seines Denkens und Werkes werden aufgezeigt. Er ist ein Referenzautor für transversales und integratives Konzeptualisieren in unserer Zeit.The text commemorates the 250th year of birth of Alexander von Humboldt, a thought leader for an ecological view of the world and an early protagonist of „transversal reason“. He is an indispensable source of ideas for the „new nature therapies“, for integrative therapy and for an ecological viewpoint in psychotherapy. Some important aspects of his thinking and work are shown from this perspective. He is a reference author for transversal and integrative conceptualization in our time.https://www.fpi-publikation.de/gruene-texte/17-2019-petzold-h-g-mathias-wiedemann-u-natur-muss-gefuehlt-werden-alexander-v-humboldt/peerReviewedpublishedVersio
„Natur muss gefühlt werden“ – Alexander von Humboldt, Vordenker einer ökologischen Weltsicht und Protagonist „transversaler Vernunft“
No full textDer Text erinnert zum 250sten Geburtsjahr an Alexander von Humboldt, ein Vordenker für eine ökologische Sicht der Welt und ein früher Protagonist „transversaler Vernunft“. Er ist als Ideengeber für die „neuen Naturtherapien“, für die Integrative Therapie und für eine ökologische Sicht in der Psychotherapie eine unverzichtbare Quelle. Einige aus dieser Perspektive wichtige Aspekte seines Denkens und Werkes werden aufgezeigt. Er ist ein Referenzautor für transversales und integratives Konzeptualisieren in unserer Zeit.The text commemorates the 250th year of birth of Alexander von Humboldt, a thought leader for an ecological view of the world and an early protagonist of „transversal reason“. He is an indispensable source of ideas for the „new nature therapies“, for integrative therapy and for an ecological viewpoint in psychotherapy. Some important aspects of his thinking and work are shown from this perspective. He is a reference author for transversal and integrative conceptualization in our time.https://www.fpi-publikation.de/polyloge/25-2019-petzold-h-g-mathias-wiedemann-u-natur-muss-gefuehlt-werden-alexander-v-humboldt/peerReviewedpublishedVersio
The reality of fiction: the ECO by Mathias Goeritz
No full textAbstract
This article covers the full biography of a building, the Experimental Museum El Eco, designed by Germanborn and Mexican émigré artist and architect Mathias Goeritz. It provides an approach intersecting the biography of the author, the history of the building, and prominent individuals of the two cultural traditions, German and Mexican, who participated in the creation of a very special and unique building: El Eco. On the one hand, the ethics of Expressionism, the interest in non-European art, the cult of primitivism and the aesthetic system of the pair of concepts abstraction-empathy, all stemming from German culture. On the other, the pantheistic religiosity of landscape, zoomorphism and anthropomorphism, the interest in masks, and the aesthetics of monumental scale, stemming from pre-Cortesian Mexican culture. Taking the stance of intertwining Mathias Goeritz parcours with those of individuals and issues from his German past and his Mexican future – highlighting the figures of Wilhelm Worringer, Paul Westheim, Luis Barragán, Edmundo O'Gorman, and Ida Rodríguez Prampolini – this article proposes a return trip from fiction to reality, following in the footsteps of the author and comparing them with the pathway of the very building El Eco
Oswald Mathias Ungers and Sol LeWitt: Variations
No full textOne of the fundamentals of Oswald Mathias Ungers work is the definition of a new unity between art and architecture. What this investigation is focused on is the identification of the intersection point between art and architecture, considering the project for the Entrance to the Kaiserthermen in Trier (20032007) as case study, revealing the system of theoretical, methodological and compositional correspondences. Plastic art is Ungers' main interlocutor: one of the author's most important references is Sol LeWitt (1928-2007), an artist he admired and collected. Setting the work of Oswald Mathias Unger and Sol LeWitt side by side, offers the opportunity to underline the shared interpretation that the two authors have of the world of forms postulated by Henri Focillon (1881-1943) in Life of Forms, according to which form, autonomous with respect to time and place, has its own universe, governed by its own laws, space and matter. According to these premises, we propose to read Trier's building through the instruments of art, following the hypothesis that in this project art embodies a creative and positive component in the definition of architecture, a cultural stimulus that guides the author in the design process
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