Novel Photochemical Methodologies for Diversity Oriented Synthesis and Screening of Combinatorial Libraries

The main goal of this project was to develop an efficient methodology allowing rapid access to structurally diverse scaffolds decorated with various functional groups. Initially, we discovered and subsequently developed an experimentally straightforward, high-yielding photoinduced conversion of readily accessible diverse starting materials into polycyclic aldehydes and their (hemi)acetals decorated by various pendants. The two step sequence, involving the Diels-Alder addition of heterocyclic chalcones and other benzoyl ethylenes to a variety of dienes, followed by the Paternò-Büchi reaction, was described as an alkene-carbonyl oxametathesis. This methodology offers a rapid increase in molecular complexity and diversity of the target scaffolds. To develop this novel methodology further and explore its generality, we directed our attention to the Diels-Alder adducts based on various chromones. We discovered that the Diels-Alder adducts of chromones are capable of photoinduced alkene-arene [2+2] cycloaddition producing different dienes, which can either dimerize or be introduced into a double-tandem [4π+2π]·[2π+2π]·[4π+2π]·[2π+2π] synthetic sequence, followed by an acid-catalyzed oxametathesis, leading to a rapid expansion of molecular complexity over a few experimentally simple steps. In view of the fact that oxametathesis previously was primarily observed in aromatic oxetanes, we decided to prepare model aliphatic oxetanes with a conformationally unconstrained or flexible methyl group based on the Diels-Alder adducts of cyclohexadiene or cyclopentadiene with methyl vinyl ketone. Upon addition of an acid, the expected oxametathesis occurred with results similar to those observed in the aromatic series proving the generality of this approach. Also we synthesized polycyclic oxetanes resulting from the Diels-Alder adducts of cyclic ketones. This not only gave us access to remarkably strained oxetane systems, but also the mechanism for their protolytic ring opening provided a great deal of insight to how the strain affects the reactivity. Additionally, we discovered that although the model Hetero-Diels-Alder adducts did not undergo [2+2] cycloaddition, both exo- and endo-Sulfa-Diels-Alder products, nonetheless, were photochemically active and various products with defined stereochemistry could be produced upon photolysis. In conclusion, we have developed an approach to the encoding and screening of solution phase libraries based on the photorelease of externally sensitized photolabile tags. The encoding tags can be released into solution only when a binding event occurs between the ligand and the receptor, equipped with an electron transfer sensitizer. The released tags are analyzed in solution revealing the identity of the lead ligand or narrowing the range of potential leads

Continuous transformation between ferro and antiferro circular structures in J1−J2−J3J_1-J_2-J_3 frustrated Heisenberg model

Frustrated magnetic compounds, in particular low-dimensional, are topical research due to persistent uncover of novel nontrivial quantum states and potential applications. The problem of this field is that many important results are scattered over the localized parameter ranges, while areas in between still contain hidden interesting effects. We consider $J_1-J_2-J_3$ Heisenberg model on the square lattice and use the spherically symmetric self-consistent approach for spin-spin Green's functions in "quasielastic" approximation. We have found a new local order in spin liquids: antiferromagnetic isotropical helices. On the structure factor we see circular concentric dispersionless structures, while on any radial direction the excitation spectrum has "roton" minima. That implies nontrivial magnetic excitations and consequences in magnetic susceptibility and thermodynamics. On the $J_1-J_2-J_3$ exchange parameters globe we discover a crossover between antiferromagnetic-like local order and ferromagnetic-like; we find stripe-like order in the middle. In fact, our "quasielastic" approach allows investigation of the whole $J_1-J_2-J_3$ globe.Comment: 9 pages, 12 figure

Thermodynamics of symmetric spin--orbital model: One- and two-dimensional cases

The specific heat and susceptibilities for the two- and one-dimensional spin--orbital models are calculated in the framework of a spherically symmetric self-consistent approach at different temperatures and relations between the parameters of the system. It is shown that even in the absence of the long-range spin and orbital order, the system exhibits the features in the behavior of thermodynamic characteristics, which are typical of those manifesting themselves at phase transitions. Such features are attributed to the quantum entanglement of the coupled spin and orbital degrees of freedom.Comment: 7 pages, 9 figures, submitted to JETP Letter

Eakate patsientide funktsionaalse võimekuse muutumine ühe aasta jooksul pärast aktiivravi traumatoloogia või orotpeedia osakonnas

http://www.ester.ee/record=b460630

Практичні аспекти моделювання режимів пневмотранспортування дрібно–штучних харчових продуктів

A mathematical and physical model of the critical pneumatic conveying modes has been developed to ensure the calculation and construction of pneumatic product pipelines of continuous operation. The model takes into consideration the technological conditions of gas suspension movement; the laws of movement of individual fine particles, accounting for their impact interaction and decompression, as well as the actual boundary conditions for a food product movement. The parameters of the zone of dynamic destruction of the layer of a small-piece food product by impact airwave were experimentally studied; the results of the calculation have been compared with the experimental data.The process of managing critical pneumatic conveying modes has been theoretically described, based on the proportional elements and feedback (a current loop of 4‒20 mA); the process of destruction of the cluster of products by airwave and controlled decompression has been studied. The process of pneumatic conveying of a small-piece product at the experimental bench system has been examined. As well as the process of moving the material in the product pipeline, which is controlled by compressed air pulses, to maintain the modes of operation.The following has been established: pressure losses caused by the movement of clean air; additional pressure losses resulting from the movement of the material; the loss of pressure required for transporting in a suspended state on a vertical stretch.A model has been developed to calculate the coordinates of a product particle when it collides with the inner surface of the product pipeline, as well as a change in its kinematic characteristics. The developed model makes it possible to determine the rational modes of pneumatic conveying and possible energy costs in the processing of various small-piece materials. The rational pneumatic conveying regimes have been determined, as well as possible energy costs in the processing of small-piece materials. As the time of supplying compressed air in the product pipeline increases, the number of product particles reaches a maximum in the range of 0.1...0.2 s. The compressed air flow rate, depending on the value of inlet mainline pressure P (0.1…0.3 MPa), is 80…160 (Nl/min). A general approach to the modeling of pneumatic conveying systems has been proposedРазработана математическая и физическая модель критических режимов пневмотранспортирования для обеспечения расчетов и конструирования магистрали пневмопродуктопроводов с непрерывным режимом работы. Модель учитывает технологические условия движения газовой суспензии; законы движения отдельных мелкоштучных частиц с учетом их ударного взаимодействия и декомпрессии, а также реальные граничные условия движения пищевого продукта. Экспериментально исследованы параметры зоны динамического разрушения слоя мелко–штучного пищевого продукта ударной воздушной волной и выполнено сравнение результатов расчета с экспериментом.Теоретически описан процесс управления критическими режимами пневмотранспортирования на основе пропорциональных элементов и обратной связи (токовая петля 4–20 мА); исследование процесса разрушения кластера продуктов с помощью воздушной волны и контролируемой декомпрессии. Изучен процесс пневмотранспортирования мелко-штучного продукта в системе экспериментального стенда. А также процесс движения материала в продуктопроводе, который управляется импульсами сжатого воздуха, для поддержания рабочих режимов.Установлены: потери давления, возникающие при движении чистого воздуха; дополнительные потери давления, возникающие при движении материала; потери давления, необходимые на транспортирования в подвешенном состоянии на вертикальном участке.Разработана модель для расчета координаты частички продукта при столкновении с внутренней поверхностью продуктопровода, а также изменение ее кинематических характеристик. Разработанная модель позволяет определять рациональные режимы пневмотранспортирования и возможные энергетические затраты при переработке различных мелко-штучных материалов. Определены рациональные режимы пневмотранспортирования и возможные энергетические затраты при переработке мелкоштучных материалов. По мере увеличение времени подачи сжатого воздуха в продуктопровод, количество частиц продукта достигает максимума в диапазоне 0,1 ... 0,2 с. Расходы сжатого воздуха в зависимости от величины входящего магистрального давления Р(0,1..0,3 МПа), составляют 80..160 (Нл/мин). Предложен подход к моделированию пневмотранспортирующих систем в целомРозроблено математичну модель критичних режимів пневмотранспортування для забезпечення розрахунків та конструювання мережі пневмопродуктопроводів із безперервним режимом роботи. Модель враховує технологічні умови руху газової суспензії; закони руху окремих дрібно–штучних частинок із врахуванням їх ударної взаємодії та декомпресії, а також реальні граничні умови руху харчового продукту. Експериментально досліджено параметри зони динамічного руйнування шару дрібно-штучного харчового продукту ударною повітряною хвилею.Теоретично описано процес управління критичними режимами пневмотранспортування на основі пропорційних елементів і зворотного зв'язку (струмова петля 4–20 мА); дослідження процесу руйнування кластера продуктів за допомогою повітряної хвилі і контрольованою декомпресії. Розглянуто процес пневмотранспортування дрібно-штучного продукту в системі експериментального стенду та процес пневмотранспортування, який керується імпульсами стисненого повітря, що обумовлюють робочі режими.Встановлені: втрати тиску, які виникають під час руху чистого повітря; додаткові втрати тиску, які виникають при русі матеріалу; втрати тиску на підтримку транспортування матеріалу у підвішеному стані на вертикальній ділянці.Розроблено модель для розрахунку координати частинки продукту при зіткненні з внутрішньою поверхнею продуктопроводу, а також зміна її кінематичних характеристик. Визначені раціональні режими пневмотранспортування і можливі енергетичні витрати при переробці дрібно-штучних матеріалів. Під час збільшення часу подачі стисненого повітря в продуктопровід, кількість частинок продукту досягає максимуму в діапазоні 0,1...0,2 с. Витрати стисненого повітря визначені в залежності від величини вхідного магістрального тиску Р (0,1...0,3 МПа) та складають 80...160 (Нл/хв). Запропоновано підхід до моделювання пневмотранспортуючих систем у цілом

Photosensitized [2 + 2] cycloaddition of N-acetylated cytosine affords stereoselective formation of cyclobutane pyrimidine dimer

Photocycloaddition between two adjacent bases in DNA produces a cyclobutane pyrimidine dimer (CPD), which is one of the major UV-induced DNA lesions, with either the cis-syn or trans-syn structure. In this study, we investigated the photosensitized intramolecular cycloaddition of partially-protected thymidylyl-(3′→5′)-N4-acetyl-2′-deoxy-5-methylcytidine, to clarify the effect of the base modification on the cycloaddition reaction. The reaction resulted in the stereoselective formation of the trans-syn CPD, followed by hydrolysis of the acetylamino group. The same result was obtained for the photocycloaddition of thymidylyl-(3′→5′)-N4-acetyl-2′-deoxycytidine, whereas both the cis-syn and trans-syn CPDs were formed from thymidylyl-(3′→5′)-thymidine. Kinetic analyses revealed that the activation energy of the acid-catalyzed hydrolysis is comparable to that reported for the thymine-cytosine CPD. These findings provided a new strategy for the synthesis of oligonucleotides containing the trans-syn CPD. Using the synthesized oligonucleotide, translesion synthesis by human DNA polymerase η was analyzed