No description available.

This thesis represents a quantum chemical treatise ofvarious types of interactions between radiation and molecularsystems, with special emphasis on the nonlinear opticalprocesses of Multi-Photon Absorption and Excited StateAbsorption. Excitation energies, transition dipole moments,two-photon and three-photon tensor elements have beencalculated from different approaches; density functional theoryandab-initiotheory, employing different orders ofcorrelation treatment with the purpose to provide accuratevalues as well as evaluate the quality of the lower ordermethods. A combined study of the Multi-Photon Absorption andExcited State Absorption processes is motivated partly becausethey both contribute to the total optical response of a systemsubjected to intense radiation, but also because of theirconnection through so-called sum-over-states expressions. Thelatter feature is exploited in a generalized few-states model,which incorporates the polarization of the light and thedirections of the transition dipole moments constructing anexcitation channel, which thereby enables a more comprehensivecomparison of the attained transition dipole moments withexperimental data. Moreover, by decomposing a complex nonlinearresponse process such as Two-Photon Absorption into moreintuitive quantities, generalized few-states models may alsoenable a more elaborate interpretation of computed orexperimental results from which guidelines can be extracted inorder to control or optimize the property of interest. Ageneral conclusion originating from these models is that thetransition dipole moments in an excitation channel should bealigned in order to maximize the Two-Photon Absorptionprobability. The computational framework employed is responsetheory which through the response functions (linear, quadratic,cubic) offers alternative routes for evaluating the propertiesin focus; either directly and untruncated through the singleresidue of the quadratic or cubic response func- tions orthrough various schemes of truncated sum-over-statesexpressions where the key ingredients, transition dipolemoments, can be identified from the single residue of thelinear response function and double residue of the quadraticresponse function. The range of systems treated in the thesisstretches from diatomics, such as carbon monoxide and lithiumhydride, via small to large fundamental organic molecules, suchas formaldehyde, tetrazine and the trans-polyenes, to largechro- mophores, such astrans-stilbene, cumulenes, dithienothiophene,paracyclophane and organo-metallic systems, such as theplatinum(II)ethynyl compounds. / QC 20120320

<p>This thesis represents a quantum chemical treatise ofvarious types of interactions between radiation and molecularsystems, with special emphasis on the nonlinear opticalprocesses of Multi-Photon Absorption and Excited StateAbsorption. Excitation energies, transition dipole moments,two-photon and three-photon tensor elements have beencalculated from different approaches; density functional theoryand<i>ab-initio</i>theory, employing different orders ofcorrelation treatment with the purpose to provide accuratevalues as well as evaluate the quality of the lower ordermethods. A combined study of the Multi-Photon Absorption andExcited State Absorption processes is motivated partly becausethey both contribute to the total optical response of a systemsubjected to intense radiation, but also because of theirconnection through so-called sum-over-states expressions. Thelatter feature is exploited in a generalized few-states model,which incorporates the polarization of the light and thedirections of the transition dipole moments constructing anexcitation channel, which thereby enables a more comprehensivecomparison of the attained transition dipole moments withexperimental data. Moreover, by decomposing a complex nonlinearresponse process such as Two-Photon Absorption into moreintuitive quantities, generalized few-states models may alsoenable a more elaborate interpretation of computed orexperimental results from which guidelines can be extracted inorder to control or optimize the property of interest. Ageneral conclusion originating from these models is that thetransition dipole moments in an excitation channel should bealigned in order to maximize the Two-Photon Absorptionprobability. The computational framework employed is responsetheory which through the response functions (linear, quadratic,cubic) offers alternative routes for evaluating the propertiesin focus; either directly and untruncated through the singleresidue of the quadratic or cubic response func- tions orthrough various schemes of truncated sum-over-statesexpressions where the key ingredients, transition dipolemoments, can be identified from the single residue of thelinear response function and double residue of the quadraticresponse function. The range of systems treated in the thesisstretches from diatomics, such as carbon monoxide and lithiumhydride, via small to large fundamental organic molecules, suchas formaldehyde, tetrazine and the trans-polyenes, to largechro- mophores, such as<i>trans</i>-stilbene, cumulenes, dithienothiophene,paracyclophane and organo-metallic systems, such as theplatinum(II)ethynyl compounds.</p>

Bioisosterism is a field that is widely applied to biological molecules, including drugs and agrochemicals. Bioisosterism is the replacement of an active fragment in a molecule with another fragment similar in activity. The replacement is designed to alter the behavior of the molecule in its target environment. In previous work a bioisostere database called the Quantum Isostere Database (QID) was built out of descriptors derived from the theory of Quantum Chemical Topology (QCT). The current work aims to expand the existing QID to include ring fragments. A series of rings were characterised by QCT properties taken from the ring. It was found that four features of a ring each independently have a systematic effect on the ring’s properties. In other words, each of the characteristics of a ring can be changed and have the same effect on the ring’s properties irrespective of the other ring features. The rings were also characterised using the three QCT properties taken from a point within the ring. The three properties established a space where rings were positioned based on their respective three properties. The positions of the rings showed that the space was able to discern between ring types, and that the features of a ring could be predicted if only its three properties were known. To improve the QID the alignment method and scoring were tested. The alignment procedure is unable to correctly align collinear fragments. Therefore, a principal axis alignment procedure was successfully employed to align collinear fragments. For terminal fragments an alternative alignment procedure was proposed to account for the increased rotational freedom. A global axis system meant that the direction dependent properties for all fragments were expressed in this new axis system. This idea was extended further and it was found that the geometry of a molecule was imprinted in the electrostatics when they were expressed in the global axis system. Finally, a pKa prediction method which correlates a single ab initio bond length was tested against two data sets (enols and guanidines). The method relies on subsets to form, where molecules within a subset share a chemical or structural commonality. These subsets were able to distinguish between the five tautomeric forms for the guanidines and different conformations for the enols. All predictions were within 1.0 pKa units of experimental values.

Gauge invariant shielding constants calculations of ?H, ?C, and ??N were calculated for acetonitrile in the gas and liquid phases. Dierent basis sets as well as dierent ab initio and DFT methods were tested to select a time-ecient level of theory with reasonable accuracy. The eect of nuclear motion on the shielding constants was also explored. To investigate solvent eects on the shielding constants of acetonitrile, dierent clusters were extracted from molecular dynamics simulations. Convergence to the experimental values varied for the dierent clusters. The geometry of the central molecule in a cluster played an important factor in reaching convergence. / Master of Science

No / Budesonide is a mixture of 22R and 22S epimers. The epimeric content of budesonide was reported in both British and European pharmacopoeias to be within the range of 60-49/40-51 for R and S epimers, respectively. In this work, contribution of the two epimers to the overall infrared spectrum of budesonide has been investigated by quantum chemical calculations.

No description available.

High-intensity light — for instance that from a laser — can be destructive, not only to the human eye, but also to equipment such as imaging sensors and optical communication devices. Therefore, effective protection against such light is desirable. A protection device should ideally have high transmission to non-damaging light, and should also be fast-acting in order to effectively stop high-intensity light. In working towards a protection device, there is a need to conduct fundamental research in order to understand the processes involved. One of the photophysical processes of special interest in the field of optical power limiting (OPL) is reverse saturable absorption, where a compound in an excited state absorbs light more strongly than it does in its ground state. In this work, several novel organoplatinum compounds for OPL, rationally designed to have a strong reverse saturable absorption, have been synthesized. The compounds have been analyzed using linear and nonlinear absorption spectroscopy, luminescence spectroscopy, and quantum chemistry calculations to gain further knowledge regarding their photophysical properties. In addition to this fundamental research, the absorption capabilities of some of these compounds indicate that they can be used for OPL applications. Consequently, compounds from these studies have been incorporated into a sol–gel glass that could be used in optical systems. / <p>Finansiellt stöd från Kempestiftelsen.</p>

In the present thesis, the reaction mechanisms of several di-zinc hydrolases have been explored using quantum chemical modeling of the enzyme active sites. The studied enzymes are phosphotriesterase (PTE), aminopeptidase from Aeromonas proteolytica (AAP), glyoxalase II (GlxII), and alkaline phosphatase (AP). All of them contain a binuclear divalent zinc core in the active site. The density functional theory (DFT) method B3LYP functional was employed in the investigations. The potential energy surfaces (PESs) for various reaction pathways have been mapped and the involved transition states and intermediates have been characterized. The hydrolyses of different types of substrates were examined, including phosphate esters (PTE and AP) and the substrates containing carbonyl group (AAP and GlxII). The roles of zinc ions and individual active-site residues were analyzed and general features of di-zinc enzymes have been characterized. The bridging hydroxide stabilized by two zinc ions has been confirmed to be capable of the nucleophile in the hydrolysis reactions. PTE, AAP, and GlxII all employ the bridging hydroxide as the direct nucleophile. Furthermore, it is shown that either one of or both zinc ions provide the main catalytic power by stabilizing the negative charge developing during the reaction and thereby lowering the barriers. In the cases of GlxII and AP, one of zinc ions also contributes to the catalysis by stabilizing the leaving group. These features perfectly satisfy the two requisites for the hydrolysis, i.e. sufficient nucleophilicity and stabilization of charge. A competing mechanism, in which the bridging hydroxide acts as a base, was shown to have significantly higher barrier in the case of PTE. For phosphate hydrolysis reactions, it is important to characterize the nature of the transition states involved in the reactions. Associative mechanisms were observed for both PTE and AP. The former uses a step-wise associative pathway via a penta-coordinated intermediate, while the latter proceeds through a concerted associative path via penta-coordinated transition states. Finally, with PTE as a test case, systematic evaluation of the computational performance of the quantum chemical modeling approach has been performed. This assessment, coupled with other results of this thesis, provide an effective demonstration of the usefulness and powerfulness of quantum chemical active-site modeling in the exploration of enzyme reaction mechanisms and in the characterization of the transition states involved. / QC 20100715 / Quantum Chemical Modeling of Binuclear Zinc Enzymes

Insight into the effect of secondary interactions, fluorination, as well as substituent effects on strong ionic hydrogen bonds has been acquired through studies of FHF-, NFnH3-n•••F- (n = 0..2) and [M-H]- (M = Glycine, Alanine, Valine, Serine) clustered with ROH (R = H, CH3, C2H5). Excellent agreement was observed between thermochemical values obtained from high pressure mass spectrometry measurements and those predicted from MP2(full)/6-311++G(d,p)//B3LYP/6-311++G(d,p) calculations. In the examination of the clustering of FHF-, a strong correlation between the hydrogen bond strength and the gas phase acidity of the solvent was observed. In addition, several interesting observations on various structural and thermochemical properties were made for each of the three solvents. Upon formation of clusters with water, it was found that the large entropic advantage of one particular structure, which was not the most enthalpically favored, was significant enough to make it the predominant species within the ion source. In the case of methanol solvation, no evidence of secondary interaction of the methyl group and any other moiety could be found. The structural details revealed from calculations of the ethanol-solvated clusters indicate that secondary interactions between the terminal methyl group and FHF- had an impact on the length of both the FHF and OHF bonds present. In an attempt to gain insight into the effects of fluorination on hydrogen bonding, clusters of NFnH3-n (n = 0..2) and F- have been computationally investigated. The hydrogen bond energy in NH3∙∙∙F-, NFH2∙∙∙F- and NF2H∙∙∙F- were calculated to be -67.9 kJ∙mol-1, -120.2 kJ∙mol-1 and -181.2 kJ∙mol-1, respectively, and clearly show the effect of fluorination on hydrogen bond strength in amine-fluoride systems. The change in enthalpy and entropy for the clustering of methanol to NF2H∙∙∙F- to form the fluoride bound dimer of methanol and difluoramine has been measured via high pressure mass spectrometry to be -68.3 kJ∙mol-1 and -90.5 J∙K-1∙mol-1. These values are in excellent agreement with the calculated analogues, -70.9 kJ∙mol-1 and -88.5 J∙K-1∙mol-1. Finally, an examination of the thermochemical properties associated with the formation of a hydrogen bond linkage between protic solvents and deprotonated amino acids has been performed. In addition to observations of the effect of side chain substitution, a comparison between measured and calculated properties has provided insight into the thermochemical effects arising from the isomeric nature of this clustering system. A new theoretical model describing the impact of a distribution of isomers on thermochemical measurements made via high pressure mass spectrometry is given. When this new model was applied, and the distribution of isomers correctly accounted for, the measured values of 〖∆H〗^°, 〖∆S〗^° and 〖∆G〗_298^° consistently agreed, to a very high degree of accuracy, with those predicted by MP2(full)/6-311++G(d,p)//B3LYP/6-311++G(d,p) calculations. As well, IR spectra for the clustering of deprotonated glycine with ROH have been calculated and analyzed to demonstrate the ability of techniques such as IRMPD to identify the presence of a distribution of isomers.