Mário T.S. Rosado

Vibrational spectra of acid and alkaline glycine salts

qy . qy . The infrared and Raman spectra of crystalline acid NH CH COOHP Cl and alkaline Na P NH CH COO 32 2 2 glycine salts were recorded and interpreted. The assignments were confirmed by comparison with the infrared and Raman q y . spectra of crystalline glycine zwitterion, NH CH COO and the infrared spectrum of this molecule isolated in an argon 32 . . matrix at low temperature 10 K neutral form, NH CH COOH . Further insight on the features of the vibrational spectra 22 ) . of these substances was achieved by ab initio HFr6-31G frequency and intensity calculations and potential energy distribution calculations resulting from normal coordinate analysis. q 1998 Elsevier Science B.V. . .

Synthesis, characterization and biodistribution of bisphosphonates Sm-153 complexes: correlation with molecular modeling interaction studies

Bisphosphonates (BPs) are characterized by a P-C-P backbone structure and two phosphonic acid groups bonded to the same carbon, and are established as osteoclast-mediated bone resorption inhibitors. The nature of the groups attached to the central carbon atom are responsible in determining the potency of bisphosphonates as anti-resorption drugs. However, it is not yet clear the exact relationship between their molecular structure and pharmacologic activities. In this study, molecular geometries of pamidronate, alendronate and neridronate, differing only in the length of the aliphatic chains, were predicted by molecular mechanics and their interactions with hydroxyapatite, the main bone mineral component, were examined. We report the synthesis and radiochemical characterization of 153Sm complexes with pamidronate, alendronate and neridronate. Hydroxyapatite binding and biodistribution studies of these complexes have shown a good correlation with the theoretical molecular modeling interaction studies. So, it is possible to conclude that computational chemistry techniques are a good approach to evaluate specific interactions and may play a relevant role in determining the relative ability of BPs to mineral bone, and open new perspectives to the design of new BPs with increased pharmacological activity. These techniques could be extended to BPs as ligands to carrier radioactive metals, aiming for new bone therapeutic radiopharmaceuticals.

Structure of isolated 1,4-butanediol: combination of MP2 calculations, NBO analysis, and matrix-isolation infrared spectroscopy.

Theoretical calculations at the MP2 level, NBO and AIM analysis, and matrix-isolation infrared spectroscopy have been used to investigate the structure of the isolated molecule of 1,4-butanediol (1,4-BDO). Sixty-five structures were found to be minima on the potential energy surface, and the three most stable forms are characterized by a folded backbone conformation leading to the formation of an intramolecular H-bond. To better characterize the intramolecular interactions and particularly the hydrogen bonds, natural bond orbital analysis (NBO) was performed for the four most stable conformers, and was further complemented with an atoms-in-molecules (AIM) topological analysis. Infrared spectra of 1,4-BDO isolated in low-temperature argon and xenon matrixes show a good agreement with a population-weighted mean theoretical spectrum, and the spectral features of the conformers expected to be trapped in the matrixes were observed experimentally. Annealing the xenon matrix from 20 to 60 K resulted in significant spectral changes, which were interpreted based on the barriers to intramolecular rotation. An estimation of the intramolecular hydrogen bond energy was carried out following three different methodologies.

Conformational Cooling Dynamics in Matrix-Isolated 1,3-Butanediol

The complete conformational space of monomeric 1,3-butanediol has been characterized theoretically, and 73 unique stable conformers were found at the MP2/6-311++G(d,p) level. These were classified into nine families whose members share the same heavy atom backbone configurations and differ in the hydrogen atom orientations. The first and third most populated backbone families are governed by the formation of an intramolecular hydrogen bond; however, the second precludes this type of interaction and was frequently overlooked in previous studies. Its stability is determined by the relatively high entropy of its main conformers. The hydrogen bonding of four of the most important conformers was characterized by means of atoms in molecules (AIM, also known as QTAIM) and natural bond orbital (NBO) analyses. Using appropriate isodesmic reactions, hydrogen bonding energy stabilizations of 12-14 kJ mol(-1) have been found. Experimentally, monomeric molecules of 1,3-butanediol were isolated in low-temperature inert matrixes, and their infrared spectra were analyzed from the viewpoint of the conformational distribution. All the relevant transition states for the conformational interconversion reaction paths were characterized at the same level of theory to interpret the conformational cooling dynamics observed in the low-temperature matrixes. The energy barriers for rotation of the OH groups were calculated to be very low (<3 kJ mol(-1)). These barriers were overcome in the experiments at 10 K (Ar matrix), in the process of matrix deposition, and population within each family was reduced to the most stable conformers. Further increase in the substrate temperature (up to 40 K, Xe matrix) resulted in conformational cooling where the medium-height barriers (approximately 13 kJ mol(-1)) could be surmounted and all conformational population converted to the ground conformational state. Remarkably, this state turned to consist of two forms of the most stable hydrogen bonded family, which were predicted by calculations to be accidentally degenerated and were found in the annealed matrix in equal amounts. All of these experimentally observed conformational cooling processes were analyzed and supported by full agreement with the theoretical calculations.

Stepwise conformational cooling towards a single isomeric state in the four internal rotors system 1,2-butanediol.

The present work explores the possibilities of the matrix isolation technique in the structural characterisation of highly flexible molecules. To date, most studies of this type were carried out on molecules with three or less internal degrees of freedom and a few (less than 10) possible conformations. The molecule of 1,2-butanediol has four conformationally relevant three-fold rotational axes, which can result in 81 possible conformations. A detailed theoretical study, at the MP2 and DFT(B3LYP) levels of theory with the 6-311 + + G(d,p) basis set, revealed that more than 20 conformers of 1,2-butanediol have relative energies in a 0-10 kJ mol(-1) range and contribute appreciably to the gas phase equilibrium at room temperature. This fact renders conformational studies of the system extremely difficult under normal conditions. However, the method of matrix isolation permits the reduction of the number of populated conformational states in the experiment at low temperature due to the effect known as conformational cooling: low energy barriers promote the relaxation of the higher energy local minima into more stable structures. As a result of massive conformational cooling occurring upon matrix deposition, only five conformers of 1,2-butanediol were retained in the samples at 10 K. These conformers were identified using a combination of FTIR spectroscopy and extensive theoretical calculations of vibrational spectra. Annealing of the matrices up to 50 K resulted in the extreme case of conformational cooling related with the depopulation of all conformers into the most stable unique structure. The observed transformations were rationalized in terms of barriers to intramolecular rotation.

Synthesis of New Metalloporphyrin Triads: Efficient and Versatile Tripod Optical Sensor for the Detection of Amines

Zinc and manganese complexes of porphyrin triads have been synthesized and are shown to be efficient as highly sensitive and selective tripod optical sensors for amines at the picomolar level.

Vibrational spectra (FT-IR, Raman and MI-IR) of α- and β-alanine

Abstract The vibrational spectra of α- and β-alaine molecules in both their zwitterionic and neutral forms are studied by FT-IR, Raman and MI-IR spectroscopy. Together with results from theoretical SCF-MO ab initio calculations, the spectroscopic data obtained under the various experimental conditions used in this study (crystalline phase; low temperature matrix isolated molecules) enable to undertake a detailed assignment of the vibrational spectra of the studied compounds.

Resolved structures of two picolinamide polymorphs. Investigation of the dimorphic system behaviour under conditions relevant to co-crystal synthesis

The polymorphism of picolinamide, one of the three isomeric pyridinecarboxamides, a group of co-formers with relevance for co-crystal research, has been investigated. Particular attention has been focused on phase transitions brought about in DSC scanning experiments or during ball mill grinding, a common strategy in co-crystal synthesis. Two polymorphs, which the Burger and Ramberger empirical rules predict to be enantiotropically related, were identified. The crystal structure of the room temperature stable polymorph II, Tfus,II = 102.0 °C, was redetermined, while that of the ambient temperature metastable polymorph I, Tfus,I = 106.4 °C, was determined for the first time. This was produced as single crystals by sublimation in an oven at 90 °C. In the crystalline structure of this polymorphic form, hydrogen bonds link the molecules in tetramers, which are then packed in piles along the a axis in an arrangement that has not been found in any of the previously solved crystalline structures of isomeric pyridinecarboxamides. Hirshfeld surface analysis was performed in order to facilitate comparison of the intermolecular contacts in both polymorphs. Ball mill grinding of commercial polymorph II gives rise to different outcomes, depending on the experimental conditions: neat grinding for 120 minutes results in conversion to polymorph I, while the addition of 10 μL of toluene, ethyl acetate, dimethylsulfoxide, methanol, ethanol or isopropyl alcohol and liquid assisted grinding stabilizes polymorph II.

CONFORMATIONAL ISOMERISM IN GLYCINE AND DITHIOGLYCINE: A COMPARATIVE MOLECULAR ORBITAL STUDY

Abstract The conformational potential energy surfaces (PES) of the neutral forms of glycine and its sulphur analogue dithioglycine (NH2CH2C(─S)SH) were studied by using ab initio (SCF-HF/6-31G) and semiempirical (AM1, PM3) molecular orbital calculations. Fully optimized molecular geometries, electric dipole moments and atomic charges were calculated for the different conformers with the various methods used. The conformational dependence of some relevant structural parameters was used to characterise the most important intramolecular interactions present in the molecules studied. In both cases, all methods predicted the planar conformer with both X─C-X-H and N-C-C─X dihedral angles equal to 0° and a Lp-N-C-C dihedral angle of 180° (X=O or S and Lp=lone pair) as the most stable form. However, important differences were found between the conformational behavior of the two molecules studied, which could be explained in terms of both the different sizes and electronic properties of the oxygen and sulphur subs...

Molecular structure and polymorphism of a cyclohexanediol: trans-1,4-cyclohexanedimethanol

This study aims to investigate the molecular structure and polymorphism of trans-1,4-cyclohexanedimethanol, including the bi-axial/bi-equatorial equilibrium and the nature of the intermolecular H-bond networks in condensed phases created by the hydroxyl group torsions. The full conformational space of the single molecule was explored by MP2 calculations, showing that the optimized bi-equatorial conformers have similar stability and the bi-axial ones have much higher energies. The hydroxymethyl substituents have preference for gauche/anti or gauche+/gauche− conformations. Polymorphic forms were generated by crystallization from solutions and by cooling the melt, which were characterized by a combination of techniques: DSC, PLTM and XRD. Two polymorphs were isolated and their crystal structures were solved by direct methods based on single-crystal X-ray analysis. Both were found to contain two of the most stable conformers found in the computational calculations. The influence of H-bonding in the polymorphic structures was verified by analysis of the structural differences between the geometries present in the polymorphs determined by XRD and their single molecule counterparts resulting from the theoretical calculations. The bi-axial conformations are destabilized over the bi-equatorial ones in isolated and crystalline forms of trans-1,4-cyclohexanedimethanol.