รายงานการวิจัยเอนไซม์ไบโอเซนเซอร์ที่ใช้ร่างแหตรึงของสารประกอบรีดอกซ์มอดิไฟล์ไคติน/ไคโตซานบนผิวคาร์บอนนาโนทิวบ์

Funded by Suranaree University of Technology budget year 201

Strategy for Engineering High Photolysis Efficiency of Photocleavable Protecting Groups through Cation Stabilization

Photolabile protecting groups (PPGs) enable the precise activation of molecular function with light in many research areas, such as photopharmacology, where remote spatiotemporal control over the release of a molecule is needed. The design and application of PPGs in recent years have particularly focused on the development of molecules with high molar absorptivity at long irradiation wavelengths. However, a crucial parameter, which is pivotal to the efficiency of uncaging and which has until now proven highly challenging to improve, is the photolysis quantum yield (QY). Here, we describe a novel and general approach to greatly increase the photolysis QY of heterolytic PPGs through stabilization of an intermediate chromophore cation. When applied to coumarin PPGs, our strategy resulted in systems possessing an up to a 35-fold increase in QY and a convenient fluorescent readout during their uncaging, all while requiring the same number of synthetic steps for their preparation as the usual coumarin systems. We demonstrate that the same QY engineering strategy applies to different photolysis payloads and even different classes of PPGs. Furthermore, analysis of the DFT-calculated energy barriers in the first singlet excited state reveals valuable insights into the important factors that determine photolysis efficiency. The strategy reported herein will enable the development of efficient PPGs tailored for many applications

Computational Design, Synthesis, and Photochemistry of Cy7-PPG, an Efficient NIR-Activated Photolabile Protecting Group for Therapeutic Applications

Photolabile Protecting Groups (PPGs) are molecular tools used, for example, in photopharmacology for the activation of drugs with light, enabling spatiotemporal control over their potency. Yet, red-shifting of PPG activation wavelengths into the NIR range, which penetrates the deepest in tissue, has often yielded inefficient or insoluble molecules, hindering the use of PPGs in the clinic. To solve this problem, we report herein a novel concept in PPG design, by transforming clinically-applied NIR-dyes with suitable molecular orbital configurations into new NIR-PPGs using computational approaches. Using this method, we demonstrate how Cy7, a class of NIR dyes possessing ideal properties (NIR-absorption, high molecular absorptivity, excellent aqueous solubility) can be successfully converted into Cy7-PPG. We report a facile synthesis towards Cy7-PPG from accessible precursors and confirm its excellent properties as the most redshifted oxygen-independent NIR-PPG to date (λmax=746 nm)

Cation delocalization and photo-isomerization enhance the uncaging quantum yield of a photocleavable protecting group

Photocleavable protecting groups (PPGs) enable the light-induced, spatiotemporal control over the release of a payload of interest. Two fundamental challenges in the design of new, effective PPGs are increasing the quantum yield (QY) of photolysis and red-shifting the absorption spectrum. Here we describe the combination of two photochemical strategies for PPG optimization in one molecule, resulting in significant improvements in both these crucial parameters. Furthermore, we for the first time identify the process of photo-isomerization to strongly influence the QY of photolysis of a PPG and identify the cis-isomer as the superior PPG. </p

Cation delocalization and photo-isomerization enhance the uncaging quantum yield of a photocleavable protecting group

Photocleavable protecting groups (PPGs) enable the light-induced, spatiotemporal control over the release of a payload of interest. Two fundamental challenges in the design of new, effective PPGs are increasing the quantum yield (QY) of photolysis and red-shifting the absorption spectrum. Here we describe the combination of two photochemical strategies for PPG optimization in one molecule, resulting in significant improvements in both these crucial parameters. Furthermore, we for the first time identify the process of photo-isomerization to strongly influence the QY of photolysis of a PPG and identify the cis-isomer as the superior PPG. </p

pH-Messung mit hoher lateraler Auflösung zur Visualisierung von pH-Modulationen auf Sensoroberflächen mittels SECM

Neben amperometrischen Biosensoren wurden insbesondere Sensoren beschrieben, bei denen eine als Folge einer biologischen Erkennungsreaktion erfolgende lokale Änderung des pH-Wertes als Meßsignal genutzt wird, wobei entweder konventionelle pH-Glaselektroden oder ISFETs als Transducer Anwendung finden. Allerdings erhält man so lediglich ein integrales Signal, das über die gesamten immobilisierten aktiven biologischen Erkennungselemente mittelt und nach geeigneter Kalibrierung Auskunft über die Konzentration des entsprechenden Substrates liefert. Die Detektion lokaler Modulationen des pH-Wertes kann demgegenüber zum einen Einblicke in die Homogenität des Immobilisates bzw. die lokale Verteilung der biologischen Aktivität bieten oder zum anderen zum Auslesen der Information von Multisensorarrays dienen. Um nun eine Ortsinformation von biokatalytisch induzierten pH-Modulationen zu erhalten, werden miniaturisierte pH-Sonden benötigt, wobei die erzielbare Ortsauflösung direkt mit der Sondengröße korreliert. Darüber hinaus müssen apparative Möglichkeiten geschaffen werden, solche pH-Sonden mit hoher Reproduzierbarkeit in einem definierten Abstand zu der zu untersuchenden Probenoberfläche zu positionieren, da als Folge von Diffusionsprozessen und Abfangreaktionen im Elektrolyt die H+-Aktivität vom Abstand zur Probe abhängig ist. Somit ergeben pH-Messungen bei nicht konstantem Abstand eine Faltung zwischen tatsächlicher H+-Aktivität und dem Abstand zwischen Probe und Sonde wieder, so daß eine eindeutige Messung nicht möglich ist