A series of 11 chiral dopants with an atropisomeric core derived from 4,4′-dihydroxy-2,2′,6,6′-tetramethyl-3,3′-dinitrobiphenyl were synthesized in optically pure form. These compounds were doped into five different smectic C (S C ) liquid crystal hosts to induce a ferroelectric S C * liquid crystal phase, and the reduced polarization P o was measured as a function of the dopant mole fraction x d over the range 0.005 < x d e 0.05. The polarization power δ p was found to strongly depend on the core structure of the S C host. For example, the dopant (+)-2,2′,6,6′-tetramethyl-3,3′-dinitro-4,4′-bis[(4-octyloxybenzoyl)oxy]biphenyl gave δ p values of <30 nC/cm 2 in a phenyl benzoate S C host and 1738 nC/cm 2 in a phenylpyrimidine S C host; the latter is one of the highest polarization power values reported thus far in the literature. In the phenylpyrimidine S C host, the polarization power was found to depend on the length of the dopant side chains and on the position of the atropisomeric core with respect to those of the surrounding S C host molecules, on the time average. The polarization power followed a trend opposite to that followed by the S C * helical pitch. Analysis of these results suggests that chirality transfer from the atropisomeric core of the dopant to those of the S C host molecules plays a key role in amplifying the polarization induced in the phenylpyrimidine host. It is likely that such intercore chirality transfer results in an asymmetric distortion of the S C * lattice, which in turn, further increases the conformational asymmetry of the chiral dopant by virtue of increased diastereomeric bias between the S C * lattice and the chiral conformations of the dopant.
The core or the building block is an important component in drug development. In this article, we propose and review p-aminobenzoic acid (PABA) as a building block used in the design of drugs or drug candidates. PABA is frequently found as a structure moiety in drugs. For example, in a database of 12,111 commercial drugs, 1.5% (184 drugs) were found to contain the PABA moiety. These drugs have a wide range of therapeutic uses, such as: sun-screening, antibacterial, antineoplastic, local anesthetic, anticonvulsant, anti-arrhythmic, anti-emetic, gastrokinetic, antipsychotic, neuroleptic, and migraine prophylactic. This article reviews the molecular targets and the mechanisms of these activities. Drugs containing PABA also show a wide range of structural diversity. Of the 184 PABA containing drugs identified, 95 different substitutions were found at the carboxylic group and 61 were found at the amino group of the building block. Substitution on the aromatic ring was also diverse. 13, 3, and 13 different side chains were found to modify positions 2, 3 and 5 of the aromatic ring respectively. In some drugs, the amino group is further substituted to form tertiary amine (4 different side chains). Substitutions at the carboxyl and amino groups of PABA are particularly suitable for the generation of combinatorial libraries. Just by reshuffling the identified side chains of the 184 PABA containing drugs, 4.5 million compounds can be generated. Consequently, PABA fits well as a building block for a general chemical library of "drug-like" molecules with a wide range of functional and structural diversity.
Four new chiral dopants containing an atropisomeric biphenyl core derived from 4,4′-dihydroxy-2,2′,6,6′-tetramethylbiphenyl with different symmetry-breaking groups at the 3,3′-positions (X ) F, Cl, Br, and Me) were synthesized in optically active form. These dopants were used to induce ferroelectric SmC* liquid crystal phases in four SmC hosts with different core structures. Polarization powers δ p were measured as a function of the SmC host and compared to δ p values previously obtained for an analogous atropisomeric dopant with X ) NO 2 . Theoretical conformational analyses for rotation of the atropisomeric cores about the C-O bonds of the ester groups linking the core to the side chains were performed at the B3LYP/6-31G(d) level and used in calculating Boltzmann-weighed statistical average transverse dipole moments 〈µ ⊥ 〉 for the core-diester units. The 〈µ ⊥ 〉 values were used to normalize δ p to study the influence of the symmetry-breaking groups X on the polar ordering of the dopants. Variations in δ p(norm) are rationalized by considering models describing either achiral or chiral distortions of the zigzag binding site model of the SmC host. Results show that the symmetry-breaking groups X exert a unique influence on polar ordering of the dopants in the phenylpyrimidine host PhP1 that is consistent with a model in which chirality transfer via core-core interactions between dopant and host molecules causes a chiral distortion of the zigzag binding site.
A novel concept, "drug evolution", is proposed to develop chemical libraries that have a high probability of finding drugs or drug candidates. It converts biological evolution into chemical evolution. In this paper, we present "hybridization" drug evolution, which is the equivalent of sexual recombination of parental genomes in biological evolution. The hybridization essentially shuffles the building blocks of the parent drugs and ought to drug(s); no drug evolution can otherwise occur. We hybridized two drugs, benzocaine and metoclopramide and generated 16 molecules that include the parent drugs, four known drugs, and two molecules whose therapeutic activities are reported. The unusually high number of drugs and drug candidates in the library encourages high expectations of finding new drug(s) or drug candidate(s) within the remaining eight compounds. Interestingly, the therapeutic applications of the eight drugs or drug candidates in the library are fairly diverse as 38 therapeutic applications and 25 molecular targets are counted. Therefore, the library fits as a general chemical library for unspecified therapeutic activities. The hybridization of other two drugs, aspirin and cresotamide, is also described to demonstrate the generality of the method.
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