Ricardo O. Freire

RM1: A reparameterization of AM1 for H, C, N, O, P, S, F, Cl, Br, and I

Twenty years ago, the landmark AM1 was introduced, and has since had an increasingly wide following among chemists due to its consistently good results and time‐tested reliability—being presently available in countless computational quantum chemistry programs. However, semiempirical molecular orbital models still are of limited accuracy and need to be improved if the full potential of new linear scaling techniques, such as MOZYME and LocalSCF, is to be realized. Accordingly, in this article we present RM1 (Recife Model 1): a reparameterization of AM1. As before, the properties used in the parameterization procedure were: heats of formation, dipole moments, ionization potentials and geometric variables (bond lengths and angles). Considering that the vast majority of molecules of importance to life can be assembled by using only six elements: C, H, N, O, P, and S, and that by adding the halogens we can now build most molecules of importance to pharmaceutical research, our training set consisted of 1736 molecules, representative of organic and biochemistry, containing C, H, N, O, P, S, F, Cl, Br, and I atoms. Unlike AM1, and similar to PM3, all RM1 parameters have been optimized. For enthalpies of formation, dipole moments, ionization potentials, and interatomic distances, the average errors in RM1, for the 1736 molecules, are less than those for AM1, PM3, and PM5. Indeed, the average errors in kcal · mol−1 of the enthalpies of formation for AM1, PM3, and PM5 are 11.15, 7.98, and 6.03, whereas for RM1 this value is 5.77. The errors, in Debye, of the dipole moments for AM1, PM3, PM5, and RM1 are, respectively, 0.37, 0.38, 0.50, and 0.34. Likewise, the respective errors for the ionization potentials, in eV, are 0.60, 0.55, 0.48, and 0.45, and the respective errors, in angstroms, for the interatomic distances are 0.036, 0.029, 0.037, and 0.027. The RM1 average error in bond angles of 6.82° is only slightly higher than the AM1 figure of 5.88°, and both are much smaller than the PM3 and PM5 figures of 6.98° and 9.83°, respectively. Moreover, a known error in PM3 nitrogen charges is corrected in RM1. Therefore, RM1 represents an improvement over AM1 and its similar successor PM3, and is probably very competitive with PM5, which is a somewhat different model, and not fully disclosed. RM1 possesses the same analytical construct and the same number of parameters for each atom as AM1, and, therefore, can be easily implemented in any software that already has AM1, not requiring any change in any line of code, with the sole exception of the values of the parameters themselves.

Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8

Metal–organic frameworks are emerging as a powerful platform for the delivery and controlled release of several drug molecules. Herein, we report the incorporation of the anti-cancer drug doxorubicin into the zeolitic imidazolate framework (ZIF-8) with high-load and progressive release. Adsorption measurements show that doxorubicin is incorporated into ZIF-8 with a load of 0.049 g doxorubicin g−1 dehydrated ZIF-8. Doxorubicin is released in a highly controlled and progressive fashion with 66% of the drug released after 30 days. We also characterize the antitumoral potential and cytotoxicity of the doxorubicin-ZIF-8 (DOXO-ZIF-8) complex towards the mucoepidermoid carcinoma of human lung (NCI-H292), human colorectal adenocarcinoma (HT-29), and human promyelocytic leukemia (HL-60) cell lines. It is shown that the complex doxorubicin-ZIF-8 exhibits lower cytotoxicity than pure doxorubicin for the tested cells, possibly due to the slower release of the incorporated drug. Furthermore, host–guest interactions have been addressed from a microscopic perspective through molecular docking simulations. In conjunction with our experimental characterization, the calculations suggest that doxorubicin binds preferentially to the surface rather than into the pores of ZIF-8, whose entry diameter is at least half the size of the shortest axis of the drug. These findings are also consistent with high-resolution X-ray crystallography and NMR spectroscopy studies of ZIF-8 which shows that this framework is very rigid under constant pressure in contrast to previous experimental and theoretical studies of ZIF-8 under gas pressure.

Sparkle/PM6 Parameters for all Lanthanide Trications from La(III) to Lu(III)

PM6 is the first semiempirical method to be released already parametrized for the elements of the periodic table, from hydrogen to bismuth (Z = 83), with the exception of the lanthanides from cerium (Z = 58) to ytterbium (Z = 70). In order to fill this gap, we present in this article a generalization of our Sparkle Model for the quantum chemical semiempirical calculation of lanthanide complexes to PM6. Accordingly, we present Sparkle/PM6 parameters for all lanthanide trications from La(III) to Lu(III). The validation procedure again considered only high-quality crystallographic structures and included 633 complexes. Sparkle/PM6 unsigned mean errors UME(Ln-L)s, corresponding to all the interatomic distances between the lanthanide ion and the atoms directly coordinated to it, range from 0.066 to 0.086 Å for Gd(III) and Ce(III), respectively. These minimum and maximum UME(Ln-L)s across the lanthanide series are comparable to the Sparkle/AM1 values of 0.054 and 0.085 Å for Ho(III) and Pr(III), respectively, as well as to the values for Sparkle/PM3 of 0.064 and 0.093 Å for Gd(III) and Pr(III), respectively. Moreover, for all 15 lanthanide ions, these interatomic distance deviations follow a γ distribution within a 95% level of confidence, indicating that these errors appear to be random around a mean, freeing the model of systematic errors, at least within the validation set. Sparkle/PM6 presented here, therefore, broadens the range of applicability of PM6 to the coordination compounds of the rare earth metals.

Theoretical and Experimental Studies of the Photoluminescent Properties of the Coordination Polymer [Eu(DPA)(HDPA)(H2O)2]·4H2O

We report on the hydrothermal synthesis of the [Eu(DPA)(HDPA)(H(2)O)(2)].4H(2)O lanthanide-organic framework (where H2DPA stands for pyridine-2,6-dicarboxylic acid), its full structural characterization including single-crystal X-ray diffraction and vibrational spectroscopy studies, plus detailed investigations on the experimental and predicted (using the Sparkle/PM3 model) photophysical luminescent properties. We demonstrate that the Sparkle/PM3 model arises as a valid and efficient alternative to the simulation and prediction of the photoluminescent properties of lanthanide-organic frameworks when compared with methods traditionally used. Crystallographic investigations showed that the material is composed of neutral one-dimensional coordination polymers infinity(1)[Eu(DPA)(HDPA)(H(2)O)(2)] which are interconnected via a series of hydrogen bonding interactions involving the water molecules (both coordinated and located in the interstitial spaces of the structure). In particular, connections between bilayer arrangements of infinity(1)[Eu(DPA)(HDPA)(H(2)O)(2)] are assured by a centrosymmetric hexameric water cluster. The presence of this large number of O-H oscillators intensifies the vibronic coupling with water molecules and, as a consequence, increases the number of nonradiative decay pathways controlling the relaxation process, ultimately considerably reducing the quantum efficiency (eta = 12.7%). The intensity parameters (Omega(2), Omega(4), and Omega(6)) were first calculated by using both the X-ray and the Sparkle/PM3 structures and were then used to calculate the rates of energy transfer (W(ET)) and back-transfer (W(BT)). Intensity parameters were used to predict the radiative decay rate. The calculated quantum yield obtained from the X-ray and Sparkle/PM3 structures (both of about 12.5%) are in good agreement with the experimental value (12.0 +/- 5%). These results clearly attest for the efficacy of the theoretical models employed in all calculations and create open new interesting possibilities for the design in silico of novel and highly efficient lanthanide-organic frameworks.

LUMPAC lanthanide luminescence software: Efficient and user friendly

In this study, we will be presenting LUMPAC (LUMinescence PACkage), which was developed with the objective of making possible the theoretical study of lanthanide‐based luminescent systems. This is the first software that allows the study of luminescent properties of lanthanide‐based systems. Besides being a computationally efficient software, LUMPAC is user friendly and can be used by researchers who have no previous experience in theoretical chemistry. With this new tool, we hope to enable research groups to use theoretical tools on projects involving systems that contain lanthanide ions.

Modeling, Structural, and Spectroscopic Studies of Lanthanide-Organic Frameworks

In this paper, we report the hydrothermal synthesis of three lanthanide-organic framework materials using as primary building blocks the metallic centers Eu(3+), Tb(3+), and Gd(3+) and residues of mellitic acid: [Ln(2)(MELL)(H(2)O)(6)] (where Ln(3+) = Eu(3+), Tb(3+), and Gd(3); hereafter designated as (1), (2) and (3)). Structural characterization encompasses single-crystal X-ray diffraction studies, thermal analysis, and vibrational spectroscopy, plus detailed investigations on the experimental and predicted (using the Sparkle/AM1 model) photophysical luminescent properties. Crystallographic investigations showed that the compounds are all isostructural, crystallizing in the orthorhombic space group Pnnm and structurally identical to the lanthanum 3D material reported by the group of Williams. (2) is highly photoluminescent, as confirmed by the measured quantum yield and lifetime (37% and 0.74 ms, respectively). The intensity parameters (Omega(2), Omega(4), and Omega(6)) of (1) were first calculated using the Sparkle/AM1 structures and then employed in the calculation of the rates of energy transfer (W(ET)) and back-transfer (W(BT)). Intensity parameters were used to predict the radiative decay rate. The calculated quantum yield derived from the Sparkle/AM1 structures was approximately 16%, and the experimental value was 8%. We attribute the registered differences to the fact that the theoretical model does not consider the vibronic coupling with O-H oscillators from coordinated water molecules. These results clearly attest for the efficacy of the theoretical models employed in all calculations and open a new window of interesting possibilities for the design in silico of novel and highly efficient lanthanide-organic frameworks.

Sparkle/PM3 for the modeling of europium(III), gadolinium(III), and terbium(III) complexes

O modelo Sparkle/PM3 e parametrizado para complexos de europio (III), gadolinio (III) e terbio (III). A validacao do modelo foi realizada utilizando noventa e seis complexos de Eu(III), setenta complexos de Gd(III) e quarenta e dois complexos de Tb(III); todos a partir de estruturas cristalograficas de alta qualidade, com fator R < 5%. Os erros medios absolutos, obtidos com o modelo Sparkle/PM3, considerando todas as distâncias interatomicas do tipo lantanideo-atomo ligante, foram 0,080 A para Eu(III), 0,063 A para Gd(III) e 0,070 A para Tb(III). Estes valores medios sao similares aos obtidos com o modelo Sparkle/AM1 (0,082 A, 0,061 A, e 0,068 A, respectivamente). Alem disso, a exatidao em reproduzir o poliedro de coordenacao de complexos de Eu(III), Gd(III) e Tb(III) e similar a obtida utilizando metodos ab initio com potenciais efetivos de caroco. Finalmente, com o objetivo de avaliar se as geometrias preditas com o modelo Sparkle/PM3 sao confiaveis, escolhemos um dos complexos de Eu(III), BAFZEO, para o qual geramos centenas de diferentes geometrias iniciais, onde variamos de forma aleatoria as distâncias e ângulos entre os ligantes e o ion Eu(III). Em seguida, todas essas geometrias iniciais foram otimizadas usando o modelo Sparkle/PM3. Como resultado, observamos uma tendencia significativa onde a geometria que apresentou o menor erro medio absoluto apresentou tambem a energia total mais baixa, o que reforca a validade do modelo Sparkle. The Sparkle/PM3 model is extended to europium(III), gadolinium(III), and terbium(III) complexes. The validation procedure was carried out using only high quality crystallographic structures, for a total of ninety-six Eu(III) complexes, seventy Gd(III) complexes, and forty-two Tb(III) complexes. The Sparkle/PM3 unsigned mean error, for all interatomic distances between the trivalent lanthanide ion and the ligand atoms of the first sphere of coordination, is: 0.080 A for Eu(III); 0.063 A for Gd(III); and 0.070 A for Tb(III). These figures are similar to the Sparkle/AM1 ones of 0.082 A, 0.061 A, and 0.068 A respectively, indicating they are all comparable parameterizations. Moreover, their accuracy is similar to what can be obtained by present-day ab initio effective core potential full geometry optimization calculations on such lanthanide complexes. Finally, we report a preliminary attempt to show that Sparkle/PM3 geometry predictions are reliable. For one of the Eu(III) complexes, BAFZEO, we created hundreds of different input geometries by randomly varying the distances and angles of the ligands to the central Eu(III) ion, which were all subsequently fully optimized. A significant trend was unveiled, indicating that more accurate local minima geometries cluster at lower total energies, thus reinforcing the validity of sparkle model calculations.

Synthesis and characterization of the europium(III) pentakis(picrate) complexes with imidazolium countercations: structural and photoluminescence study.

Six new lanthanide complexes of stoichiometric formula (C)(2)[Ln(Pic)(5)]--where (C) is a imidazolium cation coming from the ionic liquids 1-butyl-3-methylimidazolium picrate (BMIm-Pic), 1-butyl-3-ethylimidazolium picrate (BEIm-Pic), and 1,3-dibutylimidazolium picrate (BBIm-Pic), and Ln is Eu(III) or Gd(III) ions--have been prepared and characterized. To the best of our knowledge, these are the first cases of Ln(III) pentakis(picrate) complexes. The crystal structures of (BEIm)(2)[Eu(Pic)(5)] and (BBIm)(2)[Eu(Pic)(5)] compounds were determined by single-crystal X-ray diffraction. The [Eu(Pic)(5)](2-) polyhedra have nine oxygen atoms coordinated to the Eu(III) ion, four oxygen atoms from bidentate picrate, and one oxygen atom from monodentate picrate. The structures of the Eu complexes were also calculated using the sparkle model for lanthanide complexes, allowing an analysis of intramolecular energy transfer processes in the coordination compounds. The photoluminescence properties of the Eu(III) complexes were then studied experimentally and theoretically, leading to a rationalization of their emission quantum yields.

Theoretical and Experimental Spectroscopic Approach of Fluorinated Ln3+−β-Diketonate Complexes

In this paper we report the synthesis of two new complexes, [Eu(fod)(3)(phen)] and [Tb(fod)(3)(phen)] (fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octadionate and phen = 1,10-phenanthroline), and their complete characterization, including single-crystal X-ray diffraction, UV-vis spectroscopy, IR spectroscopy, and TGA. The complexes were studied in detail via both theoretical and experimental approaches to the photophysical properties. The [Eu(fod)(3)(phen)] complex crystallizes in the monoclinic space group P2(1)/c. The crystal structure of [Eu(fod)(3)(phen)] exhibits an offset pi-pi stacking interaction between the phenanthroline ligands of adjacent lanthanide complexes. The Eu(3+) cation is coordinated to three fod anionic ligands and to one phen. The symmetry around Eu(3+) is best described as a highly distorted square antiprism. The molar absorption coefficients of [Eu(fod)(3)(phen)] and [Tb(fod)(3)(phen)] revealed an improved ability to absorb light in comparison with the stand-alone phen and fod molecules. [Tb(fod)(3)(phen)] emits weak UV excitation, with this feature being explained by the triplet-(5)D(4) resonance, which contributes significantly to the nonradiative deactivation of Tb(3+), causing a short lifetime and low quantum yield. The intensity parameters (Omega(2), Omega(4), and Omega(6)) of [Eu(fod)(3)(phen)] were calculated for the X-ray and Sparkle/AM1 structures and compared with values obtained for [Eu(fod)(3)(H(2)O)(2)] and [Eu(fod)(3)(phen-N-O)] (phen-N-O = 1,10-phenanthroline N-oxide) samples. Intensity parameters were used to predict the radiative decay rate. The theoretical quantum efficiencies from the X-ray and Sparkle/AM1 structures are in good agreement with the experimental values, clearly attesting to the efficacy of the theoretical models.

Sparkle/RM1 parameters for the semiempirical quantum chemical calculation of lanthanide complexes

In this article, we present Sparkle Model parameters to be used with RM1, presently one of the most accurate and widely used semiempirical molecular orbital models based exclusively on monoatomic parameters, for systems containing H, C, N, O, P, S, F, Cl, Br, and I. Accordingly, we used the geometries of 169 high quality crystallographic structures of complexes for the training set, and 435 more for the validation of the parameterization for the whole lanthanide series, from La(III) to Lu(III). The distance deviations appear to be random around a mean for all lanthanides. The average unsigned error for Sparkle/RM1 for the distances between the metal ion and its coordinating atoms is 0.065 A for all lanthanides, ranging from a minimum of 0.056 A for Pm(III) to 0.074 A for Ce(III), making Sparkle/RM1 a balanced method across the lanthanide series. Moreover, a detailed analysis of all results indicates that Sparkle/RM1 is particularly accurate in the prediction of lanthanide cation-coordinating atom distances, making it a suitable method for the design of luminescent lanthanide complexes. We illustrate the potential of Sparkle/RM1 by carrying out a Sparkle/RM1 full geometry optimization of a tetramer complex of europium with 181 atoms. Sparkle/RM1 may be used for the prediction of geometries of large complexes, metal–organic frameworks, etc., to useful accuracy.