TY  - JOUR
AB  - Predicting the solubility and lipophilicity of platinum(II, IV) complexes is essential for prioritizing potential anticancer candidates in drug discovery. This study introduces the first publicly available online model for predicting the solubility of platinum complexes, addressing the lack of literature and models in this regard. Using a time-split dataset, we developed a consensus model with a Root Mean Squared Error (RMSE) of 0.62 through 5-cross-validation on a training set of 284 historical compounds (solubility data reported prior to 2017). However, the RMSE increased to 0.86 when applied to a prospective test set of 108 compounds reported after 2017. Further analysis of the high prediction errors revealed that these inaccuracies are primarily attributed to the underrepresentation of novel chemical scaffolds, particularly Pt(IV) derivatives, in the training sets. For instance, a series of eight phenanthroline-containing compounds, not covered by the training set's chemical space, had an RMSE of 1.3. When the model was redeveloped using a combined dataset, the RMSE of this series significantly decreased to 0.34 under the same validation protocol. Additionally, we developed an interpretable linear model to identify structural features and functional groups that influence the solubility of platinum complexes. We further validated the correlation between solubility and lipophilicity, consistent with the Yalkowsky General Solubility Equation. Building on these insights, we developed a final multitask model that simultaneously predicts solubility and lipophilicity as two endpoints with RMSE = 0.62 and 0.44, respectively. The data and final developed model is available at https://ochem.eu/article/31.
AU  - Mousa, N.*
AU  - Varbanov, H.P.*
AU  - Kaipanchery, V.*
AU  - Gabano, E.*
AU  - Ravera, M.*
AU  - Toropov, A.A.*
AU  - Charochkina, L.*
AU  - Cardoso Micu Menezes, F.M.
AU  - Godin, G.*
AU  - Tetko, I.V.
C1  - 73723
C2  - 57191
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
TI  - Online OCHEM multi-task model for solubility and lipophilicity prediction of platinum complexes.
JO  - J. Inorg. Biochem.
VL  - 269
PB  - Elsevier Science Inc
PY  - 2025
SN  - 0162-0134
ER  - 

TY  - JOUR
AB  - The zinc complexes of chloroquine (CQ; [Zn(CQH+)Cl3]) and hydroxychloroquine (HO-CQ; [Zn(HO-CQH+)Cl3]) were synthesized and characterized by X-Ray structure analysis, FT-IR, NMR, UV-Vis spectroscopy, and cryo-spray mass spectrometry in solid state as well as in aqueous and organic solvent solutions, respectively. In acetonitrile, up to two Zn2+ ions bind to CQ and HO-CQ through the tertiary amine and aromatic nitrogen atoms (KN-aminCQ = (3.8 ± 0.5) x 104 M-1 and KN-aromCQ = (9.0 ± 0.7) x 103 M-1 for CQ, and KN-aminHO-CQ = (3.3 ± 0.4) x 104 M-1 and KN-aromHO-CQ = (1.6 ± 0.2) x 103 M-1 for HO-CQ). In MOPS buffer (pH 7.4) the coordination proceeds through the partially deprotonated aromatic nitrogen, with the corresponding equilibrium constants of KN-arom(aq)CQ = (3.9 ± 1.9) x 103 M-1and KN-arom(aq)HO-CQ = (0.7 + 0.4) x 103 M-1 for CQ and HO-CQ, respectively. An apparent partition coefficient of 0.22 was found for [Zn(CQH+)Cl3]. Mouse embryonic fibroblast (MEF) cells were treated with pre-synthesized [Zn((HO-)CQH+)Cl3] complexes and corresponding ZnCl2/(HO-)CQ mixtures and zinc uptake was determined by application of the fluorescence probe and ICP-OES measurements. Administration of pre-synthesized complexes led to higher total zinc levels than those obtained upon administration of the related zinc/(hydroxy)chloroquine mixtures. The differences in the zinc uptake between these two types of formulations were discussed in terms of different speciation and character of the complexes. The obtained results suggest that intact zinc complexes may exhibit biological effects distinct from that of the related zinc/ligand mixtures.
AU  - Squarcina, A.*
AU  - Franke, A.*
AU  - Senft, L.*
AU  - Onderka, C.*
AU  - Langer, J.D.*
AU  - Vignane, T.*
AU  - Filipovic, M.R.*
AU  - Grill, P.
AU  - Michalke, B.
AU  - Ivanović-Burmazović, I.*
C1  - 69751
C2  - 55251
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
TI  - Zinc complexes of chloroquine and hydroxychloroquine versus the mixtures of their components: Structures, solution equilibria/speciation and cellular zinc uptake.
JO  - J. Inorg. Biochem.
VL  - 252
PB  - Elsevier Science Inc
PY  - 2024
SN  - 0162-0134
ER  - 

TY  - JOUR
AB  - The octanol/water partition coefficient, logP, is one of the most important physico-chemical parameters for the development of new metal-based anticancer drugs with improved pharmacokinetic properties. This study addresses an issue with the absence of publicly available models to predict logP of Pt(IV) complexes. Following data collection and subsequent development of models based on 187 complexes from literature, we validate new and previously published models on a new set of 11 Pt(II) and 35 Pt(IV) complexes, which were kept blind during the model development step. The error of the consensus model, 0.65 for Pt(IV) and 0.37 for Pt(II) complexes, indicates its good accuracy of predictions. The lower accuracy for Pt(IV) complexes was attributed to experimental difficulties with logP measurements for some poorly-soluble compounds. This model was developed using general-purpose descriptors such as extended functional groups, molecular fragments and E-state indices. Surprisingly, models based on quantum-chemistry calculations provided lower prediction accuracy. We also found that all the developed models strongly overestimate logP values for the three complexes measured in the presence of DMSO. Considering that DMSO is frequently used as a solvent to store chemicals, its effect should not be overlooked when logP measurements by means of the shake flask method are performed. The final models are freely available at http://ochem.eu/article/76903.
AU  - Tetko, I.V.
AU  - Varbanov, H.P.
AU  - Galanski, M.*
AU  - Talmaciu, M.*
AU  - Platts, J.A.*
AU  - Ravera, M.*
AU  - Gabano, E.*
C1  - 47613
C2  - 39429
CY  - New York
SP  - 1-13
TI  - Prediction of logP for Pt(II) and Pt(IV) complexes: Comparison of statistical and quantum-chemistry based approaches.
JO  - J. Inorg. Biochem.
VL  - 156
PB  - Elsevier Science Inc
PY  - 2016
SN  - 0162-0134
ER  - 

TY  - JOUR
AB  - Platinum containing compounds are promising antitumor agents, but must enter cells before reaching their main biological target, namely DNA. Their distribution within the body, and hence their activity is to a large extent determined by their lipophilicity, thus there is a strong interest to develop computational methods to predict this important property. This study analyses accuracy of five methods, namely ALOGPS, KOWWIN, CLOGP and two quantum chemical approaches, to predict octanol/water partition coefficients (logP) for sets of 43 and 12 Pt(II) complexes, collected from the literature and measured by the authors, respectively. All methods gave generally poor results with mean absolute error (MAE) of between 0.8 and 3 log units for prediction of new compounds. Extension of the ALOGPS program with data from the literature set resulted in the best prediction ability, MAE=0.46, for the measured molecules. The program was also able to correctly predict errors in calculated logP values. It is freely available for interactive use at http://www.vcclab.org.
AU  - Tetko, I.V.
AU  - Jaroszewicz, I.*
AU  - Platts, J.A.*
AU  - Kuduk-Jaworska, J.*
C1  - 1202
C2  - 25515
SP  - 1424-1437
TI  - Calculation of lipophilicity for Pt(II) complexes: Experimental comparison of several methods.
JO  - J. Inorg. Biochem.
VL  - 102
IS  - 7
PB  - Elsevier
PY  - 2008
SN  - 0162-0134
ER  -