Modulation of iron spin states in highly distorted iron(III) porphyrins: H-bonding interactions and implications in hemoproteins.

A family of five- and six-coordinated Fe-porphyrins which enable us to scrutinize the effects of non-covalent interactions on the out-of-plane displacement of iron and its spin-states and axial ligand orientation in a single distorted macrocyclic environment has been reported. Combined analysis using single-crystal X-ray structure determination and EPR spectral investigation revealed the stabilization of the high-spin state of iron in the five-coordinate complex FeIII(TPPBr8)(OCHMe2), while six-coordinate complexes [FeIII(TPPBr8)(MeOH)2]ClO4, [FeIII(TPPBr8)(H2O)2]ClO4 and [FeIII(TPPBr8)(1-MeIm)2]ClO4 stabilize admixed-high, admixed-intermediate and low-spin states, respectively. The H-bonding interactions between the weak axial H2O/MeOH and perchlorate anion resulted in an elongation of the Fe-O bond which eventually shortened the Fe-N(por) distances leading to the stabilization of the admixed spin state of iron which, otherwise, stabilizes the high-spin (S = 5/2) state only. In addition, the iron atom in [FeIII(TPPBr8)(H2O)2]ClO4 is displaced by 0.02 Å towards one of the water molecules engaged in the H-bonding interactions leading to two different Fe-O (H2O) distances of 2.098(8) and 2.122(9) Å. In contrast, iron in [FeIII(TPPBr8)(MeOH)2]ClO4 sits on the plane of the porphyrin since both the axial methanol units are engaged in similar H-bonding interactions with the ClO4- ion. Moreover, the X-ray structure of low-spin FeII(TPPBr8)(1-MeIm)2 revealed a dihedral angle of 63.0° between two imidazoles which deviates largely from the expected angle of 90° (perpendicular orientations) since the axial imidazole protons are engaged in strong intermolecular C-H⋯π interactions which thereby restrict the axial ligand movement. The complex also displays the shortest Fe-N(1-MeIm) bond along with smallest dihedral angles of 7.8° and 22.4° between the axial imidazole ring and the closest Fe-Np axis due to strong π-interactions between iron and the axial imidazole ligand. Our work highlights the influence of non-covalent interactions on the out-of-plane displacement and spin state of iron and axial ligand orientations which are indeed important steps in the functioning of various hemoproteins.

Highly Oxidized Cobalt Porphyrin Dimer: Control of Spin Coupling via a Bridge.

A cobalt porphyrin dimer is constructed in which two Co(II)porphyrins are connected covalently through a redox-active diethylpyrrole moiety via a flexible but "nonconjugated" methylene bridge. Upon oxidation with even a mild oxidant such as iodine, each cobalt(II) center and porphyrin ring undergo 1e- oxidation, leading to the formation of a 4e--oxidized cobalt(III)porphyrin dication diradical complex. Other oxidants such as Cl2 and Br2 also produce similar results. To stabilize such highly oxidized dication diradicals, the "nonconjugated" methylene spacer undergoes a facile and spontaneous oxidation to form a methine group with a drastic structural change, thereby making the bridge fully π-conjugated and enabling through-bond communication. This results in a strong spin coupling between two π-cation radicals which stabilizes the singlet state. The experimental observations are also strongly supported by extensive density functional theory calculations. The present study highlights the crucial role played by the nature of the bridge in the long-range electronic communication.

Trimester-Specific Reference Intervals for Thyroid Function Parameters in Indian Pregnant Women during Final Phase of Transition to Iodine Sufficiency.

BACKGROUND: Interpretation of thyroid function tests during pregnancy depends on gestational age, method, and population-specific reference intervals. Therefore, there is a worldwide trend to establish trimester-specific levels for different populations. The aim of this study was to establish a trimester-specific reference range for thyroid function parameters during pregnancy in Indian women. MATERIALS AND METHODS: Thyroid function tests (TSH, FT4, TT4, TT3) of 80, 76, and 73 women at 1st, 2nd, and 3rd trimester, respectively, and 168 nonpregnant women were analyzed after exclusion of low UIC(<150 µg/L) and anti-TPO positivity(>35 IU/ml). Urinary iodine excretion (UIC) was assessed in all. The 2.5th and 97.5th percentile values were used to determine the reference ranges for thyrotropin (TSH), free thyroxine (FT4), total thyroxine (TT4), and total triiodothyronine (TT3) for each trimester of pregnancy. RESULTS: The reference range for TSH for first trimester was 0.19-4.34 µIU/ml, for second trimester 0.46-4.57 µIU/ml, and for third trimester 0.61-4.62 µIU/ml. The reference range during three trimesters for FT4 (ng/dl) was 0.88-1.32, 0.89-1.60, and 0.87-1.54, for total T4 (µg/dl) was 5.9-12.9, 7.4-15.2, and 7.9-14.9. In nonpregnant women, FT4 was 0.83-1.34, total T4 was 5.3-11.8, and TSH was 0.79-4.29. The mean UIC in nonpregnant women was 176 ± 15.7 µg/L suggesting iodine-sufficiency in the cohort. CONCLUSION: The trimester-specific TSH range in pregnant women in this study is not significantly different from nonpregnant reference range in the final phase of transition to iodine sufficiency in India.