Genetic algorithm for the design of molecules with desired properties

The design of molecules with desired properties is still a challenge because of the largely unpredictable end results. Computational methods can be used to assist and speed up this process. In particular, genetic algorithms have proved to be powerful tools with a wide range of applications, e.g. in the field of drug development. Here, we propose a new genetic algorithm that has been tailored to meet the demands of de novo drug design, i.e. efficient optimization based on small training sets that are analyzed in only a small number of design cycles. The efficiency of the design algorithm was demonstrated in the context of several different applications. First, RNA molecules were optimized with respect to folding energy. Second, a spinglass was optimized as a model system for the optimization of multiletter alphabet biopolymers such as peptides. Finally, the feasibility of the computer-assisted molecular design approach was demonstrated for the de novo construction of peptidic thrombin inhibitors using an iterative process of 4 design cycles of computer-guided optimization. Synthesis and experimental fitness determination of only 600 different compounds from a virtual library of more than 10¹⁷ molecules was necessary to achieve this goal.These authors contributed equally to the results presentedThese authors contributed equally to the results presentedThese authors contributed equally to the results presentedThese authors contributed equally to the results presented     

((Fluoroformyl)imido)sulfuryl difluoride, FC(O)N=S(O)F2: structural, conformational, and configurational properties in the gaseous and condensed phases

Structural, conformational, and configurational properties of the gaseous molecule ((fluoroformyl)imido)sulfuryl difluoride, FC(O)N=S(O)F(2), have been studied by vibrational spectroscopy (IR (gas) and Raman (liquid)) and quantum chemical calculations (HF, MP2, and B3LYP with 6-31+G* and 6-311+G* basis sets); in addition, the solid-state structure has been determined by X-ray crystallography. FC(O)N=S(O)F(2) exists in the gas phase as a mixture of a favored antiperiplanar-synperiplanar form (the S=O double bond antiperiplanar with respect to the C-N single bond, and the C=O group synperiplanar with respect to the S=N double bond) in equilibrium with less abundant antiperiplanar-antiperiplanar, synclinal-synperiplanar, and synclinal-antiperiplanar structures. The crystalline solid at 163 K (monoclinic, P2(1)/c, a = 5.1323(7) A, b = 15.942(2) A, c = 16.798(2) A, beta = 95.974(3) degrees , Z = 12) consists of three similar antiperiplanar-synperiplanar forms.     

Synthesis and reactions of fluorinated iminium salts

Different methods for the preparation of fluorinated iminium salts RR¹CNR²R³⁺MF₆^? (R=R¹=F ; R²=R³=CH₃, C₂H₅ M=As, Sb 4a ? c R=H, R¹=F; R²=R³=CH₃ M=As, Sb 5a, b R=R¹=CF₃; R²=H, R³=CH₃ M=Sb 12 R=R¹=CF₃; R²=R³=CH₃ M=As 14) are reported, the spectroscopic properties (IR, NMR) of the cations of these salts are briefly discussed. By F^?-addition to these salts, $\text{e.g.}$ to 16, perfluoroalkyl-bis(alkyl)-amines ($\text{e.g.}$ (CF₃)₂CFN(CH₃)₂ 15) can be prepared; from the methylation of CF₃NCF₂ bis(trifluoromethyl) methylamine (CF₃)₂NCH₃ (11) was obtained.     

Vibrational spectra and gas-phase structure of N-methyl-S,S-bis(trifluoromethyl)sulfimide, CH3N=S(CF3)2

The molecular structure of N-methyl-S,S-bis(trifluoromethyl)sulfimide, CH3N=S(CF3)2, was determined by gas electron diffraction and quantum chemical calculations [B3LYP and MP2 with 6-31+G(2df,p) basis sets]. Furthermore, vibrational spectra, IR (gas) and Raman (liquid), were recorded. These spectra were assigned by comparison with analogous molecules and with calculated frequencies and intensities (HF, B3LYP, and MP2 with 6-311G basis sets). All experimental data and computational methods result in a single conformer with syn orientation of the CH3 group relative to the bisector of the two CF3 groups. The molecule possesses C1 symmetry, slightly distorted from CS symmetry. The N=S bond length in this compound [1.522(10) A] is longer than that in imidosulfur difluorides RN=SF2 [1.476(4) A - 1.487(5) A].     

Lithium fluoroarylamidinates: syntheses, structures, and reactions

Lithium fluoroarylamidinates [(Ar(F)C(NSiMe(3))(2)Li)(n).xD] (Ar(F) = 4-CF(3)C(6)H(4), n = 2, D = OEt(2), x = 1 (2a); n = 1, D = TMEDA, x = 1 (4a); Ar(F) = 2-FC(6)H(4), n = 2, D = OEt(2), x = 1 (2b); Ar(F) = 4-FC(6)H(4), n = 2, D = OEt(2), x = 2 (2c); Ar(F) = 2,6-F(2)C(6)H(3), n = 2, D = OEt(2), x = 1 (2d); n = 2, D = 2,6-F(2)C(6)H(3)CN, x = 2 (3d); Ar(F) = C(6)F(5), n= 2, D = OEt(2), x = 1 (2e), n = 1, D = TMEDA, x = 1 (4e); n = 1, x = 2, D = OEt(2) (5e); D = THF (6e)) were prepared by the well-known method from LiN(SiMe(3))(2) and the corresponding nitrile in diethyl ether or by addition of the appropriate donor D to the respective diethyl ether complexes. Depending on the substituents at the aryl group and on the donors D, three different types of structures were confirmed by X-ray crystallography. Hydrolysis of 2e gave C(6)F(5)C(NSiMe(3))N(H)SiMe(3) (7e) and C(6)F(5)C(NH)N(H)SiMe(3) (8e). The lithium fluoroarylamidinates 2a-2d react with Me(3)SiCl to give the corresponding tris(trimethylsilyl)fluoroarylamidines Ar(F)C(NSiMe(3))N(SiMe(3))(2) (9a-9d). Attempts to prepare C(6)F(5)C(NSiMe(3))N(SiMe(3))(2) from 2e and Me(3)SiCl failed; however, the unprecedented cage [[C(6)F(5)C(NSiMe(3))(2)Li](4)LiF] (10e) in which a fluoride center is surrounded by a distorted trigonal bipyramid of five Li atoms was obtained from this reaction.     

Diode Stack End-Pumped Nd：GdVO4 Continuous Wave Slab Laser

We report a diode stack end-pumped Nd：GdV04 slab laser with a near-diffraction-limited beam. The output power of 45.8 W at 1064nm is obtained under the pumping power of 147 W, with the optical-optical conversion efficiency of 31.2%, and the slope efficiency is 39.6%.     

Fluorescence decay time of single semiconductor nanocrystals

We present fluorescence decay measurements of single ZnS covered CdSe nanocrystals. It is shown that the fluorescence decay time is fluctuating during the investigation leading to a multiexponential decay even for a single nanocrystal. In combination with measurements of the fluorescence blinking behavior we find that a high fluorescence intensity is correlated with a long fluorescence decay time. This is consistent with a model of fluctuating nonradiative decay channels leading to variable dynamic quenching processes of the excited state.     

Chemistry of Thiazyl Fluoride (NSF) and Thiazyl Trifluoride (NSF3): A Quarter Century of Sulfur-Nitrogen-Fluorine Chemistry

Since the first sulfur-nitrogen-fluorine compounds were synthesized 25 years ago^[2], great progress has been made in this field of covalent fluorine chemistry^[3–9]. The two small molecules thiazyl fluoride (NSF) and thiazyl trifluoride (NSF₃), are key substances; nearly all sulfur-nitrogen-fluorine compounds can be derived from them.